summary 2024 02 28 29 508

MEETING OF THE ADVISORY
COMMITTEE ON IMMUNIZATION
PRACTICES (ACIP)
FEBRUARY 28-29, 2024
MEETING SUMMARY
Trade names are used for identification purposes only and do not indicate endorsement.

  WEDNESDAY: FEBRUARY 28, 2024
WELCOME AND INTRODUCTIONS
Call to Order/Roll Call
Dr. Melinda Wharton (ACIP Executive Secretary & Acting Chair , CDC) called to order and
presided over the February 28-29, 2024, Advisory Committee on Immunization Practices (ACIP )
meeting.  She made opening announcements about the availability of presentation slides on the
ACIP website and scheduled oral public sessions as well as the written public comment process and then reviewed conflict of interest policies for ACIP members.  She announced that new ACIP members have been approved by the Department of Health and Human Services (HHS) .
Official letters of invitation will be released soon to these individuals, and the ACIP looks forward
to having them join a future ACIP meeting. As allowed under the ACIP charter, the ACIP’s six
Ex O fficio members were temporarily designated as voting members. Dr. Wharton noted that
during role call and prior to the votes, she would ask that the Ex O fficio members state any
conflicts of interest (COIs). She also announced that because the process for the new ACIP
Chair to join the committee had not yet been completed, she would be chairing the meeting.
She then conducted a roll call , which established that a quorum was present. A list of Members,
Ex Officios , and Liaison Representatives is included in the appendixes at the end of this
summary document. The following COIs were identified for the first day of this meeting:
Dr. Chen is working with MassBiologics on a diarrhea therapeutic product that is funded by
the Bill and Melinda Gates Foundation. MassBiologics is a non-profit vaccine manufacturer
associated with the University of Massachusetts Chan Medical School and maker of a
diphtheria/ tetanus (DT) vaccine. Because this meeting will include a vote on the addition of
DT to the Vaccines for Children ( VFC) program, he indicated that he would recuse himself
from the VFC vote for that vaccine.
COVID -19 VACCINES
Dr. Matthew F. Daley introduced this session on behalf of the ACIP COVID -19 Vaccines Work
Group. To review current COVID -19 vaccine policy, the ACIP m et on September 12, 2023, to
review the available evidence for the updated 2023 -2024 formula of COVID-19 vaccines. At that
time, ACIP recommended an updated COVID -19 vaccine as authorized under Emergency Use
Authorization (EUA) or approved by a Biologics License Application (BLA) in persons aged ≥6
months of age. This included Moderna COVID -19 vaccine in persons ≥6 months of age, Pfizer -
BioNTech COVID -19 vaccine in persons ≥6months of age, and Novavax COVID-19 vaccine in
persons ≥12 years of ager. The recommendation also included a recommendation that
everyone ≥5 years of age get an updated dose of the 2023-2024 formula to protect against
serious illness from COVID -19 regardless of prior vaccination or infection history. Children 6
months –4 years of age were recommended to receive multiple doses of COVID -19 vaccines to
be up to date, including at least 1 dose of updated COVID -19 vaccine. Additional
recommendations were made for those who are moderately or severely immunocompromised,
who may get additional doses of updated COVID -19 vaccine.
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  Dr. Christopher Taylor (CDC/NCIRD) reported on data from the COVID -19-Associated
Hospitalization Surveillance Network (COVID -NET ). COVID -NET collects data from more than
300 acute-care hospitals in 98 counties across 13 states , includ ing about 10% of the U nited
States (US) population. Hospitalizations reported to COVID -NET include all those for which a
positive SARS -CoV -2 test result was reported within 14 days prior or during hospitalization.
Screening for SARS- CoV-2 is driven by clinical judgment and facility policies.
The majority (67%) of hospitalizations captured in COVID -NET between October 2023– January
2024 were among adults ≥65 years of age. Adults ≥75 years of age comprised 46% of
hospitalizations. Among adults ≥75 years of age during October 2022– November 2023, 25% of
COVID -19-associated hospitalizations were residents of a long-term care facility (LTCF) at the
time of admission. Among all adults hospitalized with COVID -19 for the period October
2022─ November 2023, 3.8% died in -hospital. Among those, 1.4% were 18─ 49 years of age.
The highest proportions of in-hospital deaths occurred among adults ≥65 years of age, with
5.5% of adults 65─ 74 years of age and 4.4% ≥75 years of age dying in-hospital. Among adults
ages ≥65 years of age who died in-hospital, 28% were residents of LTCFs. An examination of
death certificate data from March 2020– April 2022 found that among all deaths in adults with
COVID -19-associated hospitalization, 67% occurred in-hospital and 33% occurred ≤30 days
post-discharge. The proportion of deaths occurring post-disch arge increased with age.
For the period October 2022─ November 2023, 16% of all adults hospitalized with COVID -19
had an immunocompromising condition. These percents varied by age, ranging from 12% or 1
in 8 adults 18─ 49 years of age to 21 % in adults 65─74 years of age with an
immunocompromising condition. Looking at the proportion of COVID -19-associated
hospitalizations among adults by immunocompromised status overall and by intervention or
outcome for the period October 2022 ─November 2023, 16% of all COVID -19-associated
hospitalizations were among persons with an immunocompromising condition. Among those
admitted into the ICU, 17% had an immunocompromising condition and 28% of those who died
in-hospital had an immunocompromising condition. The most common underlying conditions
observed among hospitalized adults varied by age group.
Data pertaining to COVID -19-associated hospitalizations by vaccination status among adult age
groups were limited to October ─November 2023, given that they were the 2 months of data
available for the updated 2023-2024 monovalent dose. Overall , no more than 5% of hospitalized
adults in any age category received the updated 2023-2024 monovalent dose. The largest
proportion of hospitalized adults who received the updated monovalent dose was adults ≥65
years of age at 5% . It is important to note that these 2 months of data are preliminary data and
that continued examination of these data is ongoing.
Dr. Kevin Chatham -Stephens (CDC/NCIRD) presented COVID -19 vaccination coverage data
and attitudes and experiences regarding COVID -19 vaccination. According to CDC’s National
Immunization Survey (NIS), among adults overall, 21.9% reported being up-to-date, with a
range from 43.5% among adults ≥75 years of age down to 9.5% among adults 18 ─29 years of
age. Among children overall, 12.2% were reported to be up-to-date, with the range from 15.8%
among those 12─ 17 years of age down to 5.9% among those 6 months ─4 years of age.
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  COVID -19 vaccine coverage among adults varied by jurisdiction , ranging from 9.5% in Puerto
Rico and 10.5% in Mississippi to 41.9% in the District of Columbia ( DC). In terms of COVID-19
vaccination status and intent among adults ≥18 years of age, the percent of adults who were
vaccinated with the 2023-2024 COVID -19 vaccine gradually rose from about 3% percent in late
September 2023 to 21.9 % as of February 3, 2024. The percent of adults reporting they definitely
will get vaccinated decreased from 28.2% to 11.3%. The percent of adults reporting they
probably will get vaccinated or are unsure if they will get vaccinated has remained relatively
stable between approximately 27% to 32%. The percent reporting they probably or definitely will
not get vaccinated has also remained relatively stable between 37% to 42%.
Coverage also varied by race/ethnicity, with coverage highest amongst white non-Hispanic
adults at 24.4% and lowest among American Indian/ Alaska Native (AI/AN) adults at 11.4% ,
Native Hawaiians and Other Pacific Islanders (NH/OPI) at 14.1%, and Hispanic adults at 13.3 %.
Coverage by urbanicity was lower in rural areas at 16.8% than coverage in suburban and urban
areas at 21.3% and 29.9%, respectively. Adults with health insurance at 22.7% percent had
higher vaccination coverage than adults without health ins urance at 6.9 %. Coverage also varied
by household income, with coverage increasing with increasing income. Those with incomes
greater than $ 75,000 had the highest coverage at 26.1% percent. Coverage did not vary based
on disability status.
Data on the percent of pregnant persons 18─ 49 years of age vaccinated with a 2023-2024
COVID -19 vaccine come from the Vaccine Safety Datalink (VSD), which is a collaborative
project between CDC and integrative healthcare organizations and networks across the US that
uses electronic health data from participating sites to monitor and assess the safety of vaccines.
Overall, 12.5% of pregnant persons received an updated COVID -19 vaccine as of January 27,
2024. Coverage ranged from 4.8% among Black N on-Hispanic persons to 21.3% among Asian
persons.
How people think and feel about COVID -19 vaccines has changed since 2022. C omparing
results from January 2022 to results from January 2024 from the NIS , most Americans still
consider COVID -19 vaccines to be safe and important, but vaccine confidence has declined.
Disease risk perception has also changed, as reflected in the percentage of Americans who are
moderately or very concerned about getting COVID -19. The percent of US adults who think that
a COVID -19 vaccine is very or completely safe has declined from 67.3% to 55.6% percent. The
percent of US adults who think that a COVID -19 vaccine is somewhat or very important has
declined from 83.9% to 69.6%. The percentage of US adults who are moderately or very
concerned about getting COVID -19 has declined from 55% to 32.7%. The percent of adults
reporting that their health care provider ( HCP ) recommends the COVID- 19 vaccine decreased
from 36.1% in May 2021 to 20.4% in January 2024.
A survey was conducted by CDC, RAND, and the University of Iowa of HCP in February 2023
that involved a panel of HCP comprised of all physician specialties and other health-related
professions, such as nurses and pharmacists. Based on results for physicians who spend at
least half of their time in outpatient primary care where vaccines are administered in their
worksite, most physicians reported that they always recommend bivalent boosters , with the
highest percentage being for patients ≥65 years of age at 80.9%. Regarding the reasons HCP
(e.g., physicians, nurses, pharmacists) reported for not recommending the COVID-19 bivalent
boosters to eligible patients , the most common response was a medical reason. That was
followed by patients will refuse booster vaccination, patients are tired of hearing about COVID-
19 vaccines, and there is a high level of vaccine resistance in the community.
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      Potential reasons for primary care providers (PCP) to not stock COVID -19 vaccines included
perceived low interest for COVID -19 vaccination in the patient population, c ost of the COVID -19
vaccine and other associated vaccination costs , their healthcare system decided to not stock
the COVID -19 vaccines, and availability of the COVID -19 vaccines elsewhere in the community
(e.g., pharmacies).
Based on data from the Omnibus Surveys between November 30─ December 21, 2023 on the
acceptability of co-administration of influenza, COVID -19, and RSV vaccines, respondents were
asked, “If you were due for them and they were offered, would you get more than one of these
vaccines in the same visit: COVID -19, flu, RSV ?” Approximately 2/3 of US adults indicated they
would be open to co-administration of these vaccines .
Dr. Daley asked CDR Chatham -Stephens about racial and ethnic disparities in uptake of the
2023-2024 COVID -19 vaccine formula in the context of recognizing that low coverage overall is
the biggest problem. It seems like some disparities have returned and wondered if there was a
sense of why that is. Referring to the coverage data overall he presented for adults, Dr. Chatham -Stephens
confirmed that there were some racial/ethnic disparities. There also have been some racial and
ethnic disparities among pregnant people. However, that is not necessarily unique to the
COVID -19 vaccine. Unfortunately, similar disparities have been observed with other vaccines .
There are likely multiple reasons for this, such as disparities in access to vaccine and access to
healthcare, as well as misinformation and disinformation circulating among different populations.
Some of the disparities were mitigated to some degree during the height of the federally -
distributed COVID-19 vaccine program, but have begun to return. CDC is engaged in a number
of activities to address some of these issues .
Dr. Loehr took a moment to speak to the primary care providers of the country, pointing out that
COVID vaccine is now just a regular vaccine like vaccines for everything else and he
acknowledged that many people do not want it. However, since he has had it in his office, 2 or 3
people a day are pleased to be able to easily get the vaccine there. Anything that can be done
to lower the barrier of getting a vaccine in someone’ s arm is wonderful. Therefore, he treats
COVID vaccine like influenza and other vacci nes he offers to his patients. Some people do not
want it, but a lot of others are glad he has it in his office.
Regarding Dr. Taylor’s presentation , Dr. Long said she found it difficult to interpret the slide on
hospitalized patients and the percent who had various conditions without knowing the
population at large with these conditions in the same age groups.
Dr. Taylor indicated that the work group acknowledges this as a limitation. Early in the
pandemic, an analysis was published that paired COVID-NET data from the early months of the
pandemic through June 2020 with population-level underlying conditions that were available
through the Behavioral Risk Factor Surveillance System (BRFSS), which provides estimates of
underlying chronic conditions at a population level. That paper look ed at those risks of
hospitalization versus the risk in the population. That analysis is being updated and is
anticipated to be ready for presentation at the next ACIP meeting.
Dr. Brooks commented that they had received a lot of information with these excellent
presentations , but had to figure out the synopsis. Income reduces coverage. Insurance status
reduces coverage. Only 5% of Black pregnant women got vaccinated. Why? Lower rates among
African-Americans. He asked whether there are any data coverage in urban versus rural areas.
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    Dr. Chatham -Stephens responded that u rban and suburban residents had 21.9% and 21.3%
percent coverage respectively compared to rural respondents at 16.8%.
Dr. Kotton stressed how devastating it was to see how many elderly and immunocompromised
people are being admitted to hospital, are in the intensive care unit ( ICU), and are dying from
COVID -19. It was shocking to see that only 30% to 40% of higher-risk elderly and
immunocompromised people are getting the updated vaccine. She encouraged that during this
meeting, the ACIP provide clarity on the recommendation for an updated vaccine and for
immunocompromised individuals. In September 2023, ACIP said that they could get 2 doses of
vaccine at least 2 months apart. However, the community needs to be provided with clarity on
that because people do not understand what that recommendation means. This is a life -and-
death situation for many of the patients she takes care of.
Dr. Ruth Link -Gelles (CDC/NCIRD) shared CDC ’s current data on the effectiveness of updated
2023– 2024 monovalent XBB.1.5 COVID -19 vaccine against symptomatic SARS-CoV -2 from
several CDC vaccine effectiveness (VE) platforms.
By July─ August 2023 just before the updated vaccines were introduced, individuals in the US
had high rates of infection-induced immunity that were above 70% for all age groups and almost
90% for those 16─ 49 years of age. Infection can provide some protection from future infection.
Therefore, VE findings should be interpreted as the incremental benefit provided by COVID -19
vaccination in a population with a high prevalence of infection-induced immunity.
Data from multiple systems demonstrated that updated 2023 -2024 COVID-19 vaccination
provided increased protection against symptomatic SARS -CoV -2 infection and COVID-19-
associated emergency department (ED) and urgent care (UC) visits and hospitalizations
compared to no updated vaccine dose. Receipt of an updated dose provided protection against
JN.1, the most common circulating variant currently, as well as other circulating variants. These
are relatively early estimates from all 3 VE studies , with no substantial waning. However,
waning is expected based on past experience with COVID -19 vaccines, and CDC will continue
to monitor VE.
Dr. Lisa A. Prosser, University of Michigan, presented the results from an economic analysis of
an additional dose of COVID-19 vaccine among adults . The presentation was an extension of
an economic model that previously had been presented to the committee.  There were 2
updates to the model which were to: 1) revise the probability of hospitalization from October
2022─September 2023 to reflect more recent lower rates ; 2) adjust vaccine impact for
seasonality ; and 3) add a new intervention strategy to include an additional dose of vaccine
approximately 6 months following an additional dose , referred to as the 2-dose strategy.
Incremental cost-effectiveness ratios (ICERs ) were calculated comparing an updated mRNA
booster 1-dose strategy to no booster, using the updated hospitalization and seasonality -
adjusted vaccine impact inputs. This analysis also provided ICERs for the base case and
uncertainty analyses comparing 1-dose, 2-dose, and no booster vaccination strategies.
Updating the model to include revised hospitalization rates and seasonality -adjusted vaccine
impact yield ed slightly higher ICERs for all age groups compared to the September 2023
analysis. In the updated analysis, the ICER for the 1-dose strategy for adults 18─ 49 years of
age was roughly $163,000 per QALY gained. For adults 50─64 years of age, it was about
$80,000 per QALY gained. For individuals ≥65 years of age, 1 dose of an updated vaccine was
no longer cost-saving but yielded an ICER of about $12,000 p er QALY .
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   In terms of the 2-dose strategy, the ICER was greater than $1.3 million per QALY for adults
18─49 years of age, greater than $700,000 per QALY for adults 50─64 years of age, and great
than $255,000 per QALY for adults ≥65 years of age using base-case assumptions.
Varying the probability of hospitalization had a substantial impact on the results. For probability
of hospitalization from 2 to 4 times the base case, the incremental cost-effectiveness ratios
dropped to about $120,000 per QALY at 2 times the base case, $65,000 per QALY at 3 times
the base case, and $34,000 per QALY at 4 times the base case. These higher rates correspond
to underlying condition: chronic obstructive pulmonary disease (COPD) , history of stroke,
coronary artery, asthma, hypertension, obesity, diabetes, chronic kidney disease (CKD) , and
severe obesity.
Lower costs of vaccination also were associated with lower ICERs . Varying only the cost of the
vaccine dose would move a 1-dose strategy into the cost-saving range for cost per dose of $20
or $60 per dose. The ICER for a 2-dose strategy would fall below $150,000 per QALY for a cost
per dose of $60 or less. Varying all vaccination-related costs to lower bounds yield ed cost
savings for a 1-dose strategy and about $51,000 per QALY for the 2-dose strategy.
Dr. Kotton asked Dr. Prosser whether immunocompromised persons were included in the
modeling. Dr. Prosser indicated that immunocompromised individuals were not explicitly considered in this
analysis , so these results should be considered to apply to the immunocompetent population.
Some inferences were drawn to the extent possible from the higher hospitalization rates or other
higher -risk scenarios that might correspond to immunocompromised population, but those were
not explicitly defined in that way.
Referring to Dr. Link -Gelles’s presentation, Dr. Daley noted that there may be a perception in
the public that vaccines are getting less effective. Comparing the news of November 8, 2020,
when they heard that these vaccines were 94% to 95% percent effective, 50% effectiveness is
not that compelling. As D r. Link -Gelles has explained, those are completely different because
now the vaccinated have a history of multiple vaccines plus infection and the unvaccinated
comparison group has some immunity. He wondered how to convey that 50% VE in this context
still prevents negative outcomes, such as hospitalizations and deaths.
Dr. Link -Gelles emphasized the importance of the context. Early in the pandemic, most of the
population had yet to be infected and had received zero doses of vaccine collectively. The
vaccine had the opportunity to protect almost absolutely, which was reflected in the clinical trials
with VE in the 90% range. There was nowhere to go but up in terms of collective immunity from
COVID -19. At this point in the pandemic, most people in the population have been infected.
Adding the people who have been vaccinated and not infected reaches about 98% who have
some type of prior immunity from infection, vaccination, or both. That provides protection
against future infection and future severe disease, but it does not protect absolutely. In that
context, vaccines are now providing an incremental or extra benefit beyond whatever benefit someone has remaining from their past infection or past vaccination. It is known that protection
wanes from past vaccination and past infection. Over time, whether someone has been infected
or vaccinated multiple times, their protection will decrease. Vaccines can then provide important
extra protection in terms of boosting whatever protection one has. That is important for all
people in the US, especially those who are at the highest risk such as pregnant people, people
with high-risk conditions, and individuals ≥65 years of age.
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 Even in the context of prior infection and prior vaccination, people are getting infected, being
hospitalized, having critical illness , and dying. The vaccine gives them extra protection,
particularly those who have high-risk conditions .
Dr. Long asked whether the 50% of the population with a lowered chance of being hospitalized
were used in the cost-effectiveness model .
Dr. Link -Gelles clarified that the estimates from the cost-effectiveness model came from the IVY
and VISION Networks. While those data were slightly older data, they were essentially the same
and c ost-effectiveness of the booster was reasonable.
Dr. Megan Wallace (CDC/NCIRD) presented the Evi dence to Recommendations (EtR)
Framework for the policy question, “Should persons ages 65 years and older be recommended
for an additional dose of 2023-2024 formula COVID -19 vaccine?” The additional dose should be
at least 4 months after receipt of the previous updated COVID-19 vaccine dose. As a reminder,
the currently authorized and approved 2023-2024 formula COVID -19 vaccines include Moderna,
Novavax, and Pfizer-BioNTech vaccine. This policy question would apply to all 3 of these
vaccines. ACIP recommended the 20 23-2024 formula COVID -19 vaccine in September 2023.
This session focused on whether an additional dose should be recommended in older adults
this year.
There are already recommendations for additional doses of the 2023-2024 formula COVID -19
vaccine among people who are moderately or severely immunocompromised, who have the
option to receive 1 additional dose of updated COVID-19 vaccine at least 2 months following the
last recommended updated COVID -19 vaccine dose. Further additional doses may be
administered, informed by the clinical judgment of a healthcare provider and personal
preference and circumstances. Any further additional doses should be administered at least 2
months after the last updated COVID -19 vaccine dose.
To summarize the public health problem, COVID -19 hospitalizations peaked in late December
2023─ early January 2024. However, there are still approximately 20,000 new hospital
admissions and 2,000 deaths due to COVID -19 each week. Persons ≥65 year of age have the
highest COVID -19 hospitalization rates, and hospitalization rates within this age group increase
with increasing age. Persons ≥75 years of age have the highest COVID -19 mortality rates.
Immunosenescence and higher prevalence of vaccine-only immunity in older adults compared
to younger adults suggest that more frequent doses may be needed to maintain protection in this population. While there are increases in COVID -19 during respiratory virus season, COVID -
19 hospitalizations and deaths continue throughout the year due to ongoing circulation of SARS- CoV-2. Inequities in COVID -19 hospitalizations by race and ethnicity continue and should
be considered in the context of an age-based recommendation. The work group agreed that
COVID -19 disease among persons ≥ 65 years of age is of public health importance.
For benefits and harms, Dr. Wallace summarized evidence that 2023-2024 formula COVID -19
vaccination provided increased protection against symptomatic SARS -CoV -2 infection and
COVID -19-associated ED/UC visits and hospitalizations compared to no updated vaccine dose.
COVID -19 VE from previous vaccine formulations has waned over time but appears more
durable against critical illness. An additional dose of 2023-2024 formula may restore VE, which
is expected to wane, providing additional protection until the next updated vaccine is available. COVID -19 vaccines have a favorable safety profile. Local and systemic symptoms have been
reported following receipt of COVID -19 vaccines. However, symptoms are less frequent and
severe among older adults compared with adolescents and younger adults.
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 The available data do not provide clear and consistent evidence of a safety issue for ischemic
stroke with bivalent mRNA COVID -19 vaccines, either when given alone or when given
simultaneously with influenza vaccines. The work group determined that the desirable
anticipated effects were moderate and that the undesirable anticipated effects were small. A
minority of work group members were of the opinion that the undesirable anticipated effects were minimal. The work group felt that the desirable effects outweigh the undesirable effects.
For the values domain , adults ≥65 years of age were more concerned about COVID -19 disease
and had higher confidence in vaccine safety and vaccine importance than those < 65 years of
age. Black adults were more concerned about COVID -19 disease than people of other racial
and ethnic groups. Confidence in COVID -19 vaccine safety and importance varied by race and
ethnicity. Half of adults reported that they planned to take precautions because of COVID-19
during the f all and winter months, with 41% of adults ≥65 years of age and older planning to
avoid large gatherings. Larger proportions of Black and Hispanic adults reported that they
planned to take precautions against COVID -19 than w hite adults. The work group’s opinion was
that older adults feel that the desirable effects are large compared to the undesirable effects.
Regarding whether there is important uncertainty about, or variability in, how older adults value the main outcomes, the majority opinion of the work group was that there probably is important
uncertainty or variability, and the minority opinion was that there is probably no important
uncertainty or variability.
The vaccine coverage data presented provided evidence to support acceptability.  As of
February 2024, vaccination coverage with the 2023-2024 COVID -19 vaccine was highest
among older adults 65─74 years of age and ≥75 years of age compared to younger age groups.
Disparities in COVID -19 vaccine coverage have been observed across many demographic
factors, including race, ethnicity, insurance status, and rurality. Adults who were vaccinated or definitely plan to get vaccinated were more likely to report that a healthcare provider recommended that they get a COVID -19 vaccine. Adults ≥65 years of age were more likely to
report HCP recommendation than younger adults. Among adults ≥65 years of age who had
already received a 2023- 2024 formula COVID -19 vaccine dose, 68.4% percent reported that
they definitely would get an additional dose of 2023-2024 formula COVID -19 vaccine if it is
recommended for them. The majority of work group members thought recommending an
additional dose of 2023- 2024 formula COVID -19 vaccine for older adults probably would be
acceptable to key stakeholders .
For feasibility, Dr. Wallace reminded the committee that COVID -19 vaccines are currently on the
commercial market and an ACIP recommendation would be needed for insurance coverage of
an additional dose. An additional dose recommendation would leverage existing infrastructure and vaccine product. However, it would add complexity to the current recommendations, which
could enhance vaccine and system fatigue. Access -related barriers to COVID -19 vaccines and
disparities in vaccine uptake remain. Additional dose recommendations may further heighten those inequities, but lack of recommendation limits access to those able to pay for vaccine out
of pocket. The work group’s opinion was that an additional dose of the 20 23-2024 formula of
vaccine probably would be feasible to implement among older adults.
In terms of the resource use domain, the full economic analysis presented by Dr. Proser
showed that an additional dose among adults ≥65 years of age had an ICER of about $ 250,000
per QALY . However, the ICERs became more favorable in scenarios that approximated the
higher risk, which may be seen with underlying medical conditions or advanced age.
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 An additional dose of COVID -19 vaccine is likely more cost-effective in populations with a higher
prevalence of risk factors, such as underlying conditions, which increase their probability of
hospitalization due to COVID -19. When asked whether an additional dose of the 20 23-2024
formula COVID -19 vaccine in older adults is a reasonable and efficient allocation of resources ,
the work group response was “probably yes.”
To summarize the work group interpretations , the greatest benefit of a vaccine dose would be in
those who have not yet received a 2023-2024 formula dose, particularly older adults and those
with underlying medical conditions. The data presented during this session emphasize the
importance of any dose of updated COVID -19 vaccine in older adults. Risk of severe illness due
to COVID -19 continues throughout the year and is highest in those ≥ 65 years of age. Within
adults ≥65 year of age, risk increases with increasing age. Receipt of the 2023-20 24 formula
COVID -19 vaccine provides protection against JN .1 and other circulating variants. However, VE
is expected to wane. In the past, greater durability has been observed in the protection against
critical illness. A “may ” recommendation would provide flexibility for older adults to obtain an
additional dose if they or their HCP feel they would benefit. The most benefit would likely be in
those with underlying medical conditions, advanced age, or circumstances that may increase risk, such as being a nursing home resident. An additional dose in adults ≥65 years of age may
restore protection that has waned. However, this will be a smaller incremental benefit on top of
the protection that is still being provided by the initial 2023-2024 formula COVID -19 vaccine
dose. The cost-effectiveness of an additional dose depends on COVID -19 hospitalization rates
in the coming months and the patient risk factors for severe illness due to COVID -19. As
COVID -19 epidemiology changes with time, additional dose recommendations may not be
needed in the future.
When considering an additional dose recommendation, the work group felt that a “may ”
recommendation would provide flexibility for those ≥65 years of age to get an additional dose if
they or their HCP feel they would benefit. For the overall balance of consequences, the work
group was split between judgments that “the balance between desirable and undesirable
consequences is closely balanced or uncertain” and “desirable consequences probably
outweigh undesirable consequences in most settings.” For type of recommendation, the majority
polled to recommend the intervention for individuals based on shared clinical decision-making,
which for COVID -19 vaccines has typically been referred to as a “may ” recommendation. The
proposed ACIP language is as follows:
ACIP recommends that persons ≥65 years of age may receive an additional dose of the
2023-2024 formula COVID -19 vaccine.
The proposed Clinical Considerations language is as follows:
People ages 65 years and older may receive 1 additional dose of any updated (2023– 2024 Formula) COVID -19 vaccine (i.e., Moderna, Novavax, Pfizer -BioNTech), informed
by the clinical judgement of a healthcare provider and personal preference and circumstances. Considerations for the additional dose may include a person’s risk for
severe COVID -19 due to age and the presence of underlying medical conditions. The
additional dose is administered at least 4 months following the previous dose of updated
(2023– 2024 Formula) COVID -19 vaccine.
Dr. Loehr asked whether the work group considered recommending this for people ≥ 75 years of
age, given that there seems to be a fairly dramatic change between 65 and 75.
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  Dr. Wallace indicated that the work group did have considerations of other age groups, including those ≥75 years of age. One of the key drivers that led to dropping it down to ≥65 years of age
was the equity concerns that people ≥75 years of age would likely cause inequities for those in
minority groups that are still experiencing severe illness in persons 65─74 years of age.
Dr. Long said it seemed like it would be difficult to inform providers on what they ought to do with this recommendation as far as timing, and whether certain people should be given the booster now or wait to see what is occurring with the epidemiology and give it closer to when
they might be at more risk.
Dr. Loehr said he was wrestling with “ should” versus “may ” because he was thinking that there
is a fair amount of benefit, and he tends to be more flexible. While “should” was appealing to
him at this point, he also could see many reasons why “may ” would makes sense, including
cost-effectiveness and seasonality. In his personal opinion, he probably would give this again in
February or March for those people who are particularly high risk (e.g., those ≥75 years of age,
immunocompromised persons, those with high-risk conditions ).
Dr. Kotton said she had similar thoughts as Dr. Loehr. From her perspective as an active
clinician in the field, many people she has spoken with did not even know that they should have
had an updated vaccine since September 2023. “May” seemed too soft to her, especially for the
most vulnerable populations. The American public is not aware of the fact that they actually
should be getting these vaccines. They should have already had the 2023-2024 updated
vaccine, but the majority have not. From a public health perspective, she would be concerned if
ACIP did not make a clear-cut recommendation. She would advocate for clarity for “should” get
the updated vaccine, which was what ACIP said in September 2023, and people in the highest
risk groups “ should” get an additional dose. Furthermore, also advocated for clarity and
simplicity in terms of the issue of 4 months after the prior dose and 2 months for
immunocompromised after the last dose, which is confusing to clinicians.
Dr. Cineas voiced her agreement with Dr. Kotton about harmonizing “should” for both the first
and second dose to make it easier for providers in counseling patients and to enhance uptake
among those who may be getting their first updated vaccine.
Dr. Brooks noted that the work group discussed "should" versus "may ." In terms of the potential
cons, beyond the science, it is still necessary to get the population vaccinated. There is now
more vaccine hesitancy , vaccine fatigue, and lack of confidence in a single dose. People under
65 years of age will wonder why they do not get the vaccine. Allowing for the flexibility of "may"
versus "should" may get more people vaccinated, including those <65 years of age,
immunocompromised, and those ≥65 years of age.
Dr. Loehr said that while he appreciated that perspective, most people com e in either wanting
the vaccine or not. They do have the data for people who have already gotten their 2023-2024
formula, 68% of whom would be happy to get a booster if they knew it was recommended. He
was thinking more about making it easier for providers to recommend this for everyone who walks in the door who fits the criteria. While he was not yet sure how he would vote, he did not think a “may” recommendation would get more people vaccinated.
11

 Dr. Daley acknowledged that the work group considered a number of these options, and there
was some difference of opinion among work group members. In some ways , a "may"
recommendation was a reflection of some difference of opinion on the part of the work group.
Everyone recognizes that communication is key and that how strongly a provider endorses this
in their practice is really important. It is also important to recognize that vaccination is giving in
many settings now, such as pharmacies, where long conversations might not be possible. It
might be harder to communicate a "may" recommendation than a "should" recommendation, which might be a shorter conversation of, “You should get your vaccine today .”
Dr. Loehr moved that ACIP accept the language as presented, specifically saying "may" receive an additional dose. Dr. Brooks seconded the motion.
Dr. Kotton made a motion to strengthen the language to read "should" rather than "may." Dr.
Long seconded the motion. Dr. Daskalakis echoed what Dr. Daley said about "may" providing permissiveness for people
who are already very connected to and interested in vaccination. He also agreed with Dr.
Kotton’s comment that it is important to do better in terms of communicating the importance of
the initial dose. More absolute statements around vaccines sometimes will create a chilling
effect for the folks who have not been vaccinated. In this scenario, it may be worth thinking
about the population of folks who have already been vaccinated, who are suggestible for a
vaccine, and who will likely take this recommendation on the value of an additional dose as something that may be right for them .
Dr. Kotton said that as a clinician who provides a tremendous number of vaccines to adults, she has not necessarily found that to be true in her practice. When CDC says "may," some people
do not think that means anything and does not mean someone needs to do it. “Should” is quite clear. She would like additional data to back up that in this scenario, the focus should be on those who are already vaccinated.
Dr. Long thought perhaps they were getting too hung up on “should” and asked whether “may”
could be deleted so that the statement simply read, “ACIP recommends that persons ≥65 years
of age receive an additional dose of the 2023-2024 formula COVID -19 vaccine.” This way, the
implication would be “should.”
Dr. Wharton said she thought that would be acceptable language for an ACIP recommendation,
although it was not how many other vaccine recommendations have been worded. However,
that would be an amendment.
Dr. Kotton requested clarity on the work group interpretation. The work group interpretation on
Slide 77 states, “We recommend the intervention for individuals based on shared clinical
decision-making.” That was not actually the proposed voting language for the vote. She asked
whether they actually would be recommending the somewhat dreaded shared clinical decision-
making, which makes vaccine implementation very challenging.
Dr. Wharton clarified that the “may” language as the COVID vaccine recommendations have
been made over the last couple of years is a shared clinical decision-making recommendation.
For plain language purposes, it has been worded as proposed. From an implementation perspective, this is a shared clinical decision-making recommendation.
12

  Dr. Loehr asked for clarity on whether they would first vote on the amended recommendation using the word “should” and then carry forward the final language to the afternoon voting
session.
Dr. Long requested more time to hear other opinions before voting on the amendment to the
language. Dr. Wharton clarified that the “should" recommendation from the fall for everyone to receive a
single updated dose still stands and would not be replaced by this vote in anyway. Everyone
should still get their updated 2023-2024 vaccine.
Dr. Chen said he was struck by the fact that, even though there is a waxing and waning of the
burden of disease, it really did not completely disappear. It is probably lost, even on some
clinicians, that there are significant hospitalizations and deaths even in the summer. The burden
of disease, risks associate d with age, and other underlying conditions also motivated him to see
the importance of how the second booster dose could have a significant improvement in the
population who receives it . Therefore, he favored the change to "should." Having heard that this
vote is applicable to a very small portion of the population, he was now stuck and was thinking
that the "may" language would be okay. However, he still wanted to make clear that vaccination
is extremely important and whatever they can do to improve language overall to increase
clinicians to be motivated to give a very strong recommendation to their patient population in
addition to all patients understanding the importance of vaccination would be a goal.
Dr. Wharton clarified that they would be voting first on the amended language that would
replace "may" with "should." If that amendment passed, the amended language would be taken
forward for a vote in the afternoon following public comment. If the amendment fail ed, they
would return to the original motion that had the "may" language.
Dr. Fryhofer (AMA) said that speaking as a practicing physician and a member of the COVID Vaccine Work Group , she found the day’s discussion very helpful. There is still so much
preventable disease, because COVID does not have a defined seasonality like influenza and
there are still many hospitalizations and deaths that could be prevented. She appreciated Dr.
Daskalakis ’ comment about the people who are against vaccines and how a "should"
recommendation might affect them. However, a "should" recommendation does support vaccine
confidence and the belief that this vaccine will save lives, prevent hospitalizations, and prevent
deaths. She worries about shared clinical decision-making, or a "may" recommendation,
because many people are getting vaccines in pharmacies. There is still confusion about what
pharmacies can and cannot administer, and they do not have the knowledge of a patient's
medical conditions and chronic illnesses like their personal physician or provider does. She was very impressed with Dr. Kotton’s and Dr. Long's comments, which changed the way she was
thinking about this voting language.
Dr. Schmader (AGS) said that from a geriatrics perspective and within a society, talking with patients and geriatricians, there is a wide variety of opinions about this that land toward "should"
but at least "may." "May" has to do with uncertainty about disease burden and effectiveness.
There is definitely a subset of people with vaccine fatigue and inertia. Some of the individuals in
this subset will go out right away and get the vaccine and others will not. A lot of people are thinking that there will be a vaccine in the fall, so they will just wait for that.
13

  Dr. Hopkins (NFID) said he thought this very important discussion would affect many people in
the population. While it is important to think about this additional dose, it needs to be coupled
with very strong language from ACIP and the liaisons to make sure that those who have not
received a first dose of the 2023-2024 vaccine get that. Efforts must be made to better protect
those ≥ 65 years of age, and acknowledging Dr. Kotton's comments, the immun ocompromised
population needs additional protection.
Dr. Rockwell (AAFP) said that speaking as a clinician and for private practice physicians, she
thought the stronger language of "should" was better because it helped take out some of the
ambiguity about the "may." In scholarly work and academics, they understand that. It also helps
with EHRs when there are best practice alerts.
Dr. Goldman (ACP) said that as a practicing internal medical physician, he thought jurisdictions
have different populations that can create some contention around vaccines. The "may"
recommendation can be more effective as far as explaining the need for vaccine and the
flexibility to practicing physicians in different areas. While he does think this is an effective
vaccine and there is still vaccine-preventable disease, with the issues of vaccine fatigue and the
contention that this particular vaccine has c reated over the years, having a "should" vaccination
recommendation may actually create other issues with getting the rest of patients vaccinated as
necessary for other recommended vaccines on the schedule. He suggested "may" because that
could at least give the flexibility for the practicing physician to be able to have the conversation
with the patient and separate it from issues of other vaccines they need to get as well .
Ms. Howell (AIM) noted that with long -term care residents being at high risk for severe
outcomes due to COVID-19, she wondered whether with a "may" recommendation, there would
still be a requirement for LTCFs to offer COVID -19 vaccine to their residents or if it need to be a
"should" recommendation for that to happen.
Dr. Wallace said she thought that LTCF could offer the vaccine to their residents under either
recommendation, and they certainly would fall into the high-risk category that would be
particularly important under a "may" recommendation.
As a reminder, Dr. Kotton made a motion to strengthen the language to read "should" rather
than "may." Dr. Long seconded the motion. The motion passed with 12 affirmative votes and 1 abstention to take the following language forward for a vote:
ACIP recommends that persons ≥65 years of age should receive an additional dose of the 2023-2024 formula COVID -19 vaccine.
As a point of clarification, Dr. Kotton asked whether they would be voting on the
immunocompromised and the second dose.
Dr. Wharton said that they would not be voting on this but would ask the team how this might be
handled in the context of clinical considerations to make guidance clearer.
Dr. Lakshmi Panagiotakopoulos (CDC/NCIRD) presented the next steps for the COVID -19
vaccine program , beginning by discussing the question, “Can we improve the current COVID -19
vaccine policy timeline? ” In Fall 2023, the COVID -19 vaccine policy decision occurred as
follows. The mRNA updated 2023-2024 formula vaccines were authorized or approved on
September 11, 2023. The ACIP met September 12, 2023, to review the available evidence for
the updated COVID -19 vaccines.
14

 During that meeting, ACIP recommended the updated COVID-19 vaccines as authorized under
EUA or approved by BLA in persons ≥6 months of age. Moderna and Pfizer -BioNTech vaccines
were recommended for person ≥6 months of age and the Novavax COVID -19 vaccine, which
was authorized for use on October 3, 2023, was recommended in persons ≥12 years of age. Of
note, there was a general expectation that vaccines would be widely available immediately
following the recommendations.
In fall 2023, there was uncertainty around the recommendations prior to the meeting, which
made planning for state and local vaccine programs challenging. Vaccine orders had to be
placed prior to knowing the groups for whom the vaccine would be recommended. Stakeholder
presentations, provider toolkits, and webpages all had to be updated after the recommendation was made, which limited the available window for communication of the recommendation prior to the respiratory virus season. There were also reports of issues with vaccine access, including
among those at highest risk of severe illness.
A revised timeframe for the 2024-2025 COVID -19 vaccine vote and recommendation during the
June meeting would allow for more lead time between when a recommendation is made to
when vaccines are manufactured and distributed. The proposed plan for 2024 would include a
June ACIP meeting to review the evidence for updated COVID-19 vaccine recommendations,
which would include World Health Organization ( WHO) and Food and Drug Administration
(FDA ) antigen selections, manufacturer studies , immunogenicity data, cumulative effectiveness
and safety data, epidemiology from current and prior years, uptake from current and prior years ,
and cost-effectiveness analyses . ACIP would then vote on the updated COVID-19 vaccine
recommendations in June. The 2024-2025 formula would become available as regulatory
actions are taken by the FDA and vaccines are distributed by manufacturers.
One of the biggest benefits of a June COVID -19 vaccine policy decision is that it would enable
early planning across the entirety of the healthcare delivery system, including national, state,
and local public health departments; large and small practices; and other venues for vaccine
delivery, such as pharmacies. Another benefit is that it would allow time for clear communication
of recommendations. It also would provide vaccine sites with earlier information on which to
base vaccine ordering decisions. Vaccines potentially could become available immediately
following FDA authorization or approval.
There are over 4 years of data on COVID -19 and over 3 years of data on COVID -19 vaccines .
There is a well -established precedent from the influenza vaccine recommendations. The
influenza virus also evolves rapidly and requires updates to vaccine antigens. It is unlikely there
will be more data between June and September that would influence the updated COVID -19
vaccine policy decision. The increased lead time would ease implementation challenges for
vaccine providers, including earlier information on vaccine recommendations to inform ordering,
which would allow providers to recommend the vaccine in anticipation of availability, train staff
to counsel patients who are making appointments for influenza vaccine, and make informed
decisions. The increase lead time also would allow for clearer messaging in provider and patient
educational materials.
This plan was presented to the COVID-19 ACIP Work Group. Work group members were in
favor of moving the decision to June and discussed many ways that this could ease
implementation challenges, including clearer communication of vaccine policy and increased
lead time for clinicians. Work group members emphasized that communication surrounding a recommendation prior to vaccine availability, as done routinely for influenza vaccine, will be
important.
15

   Dr. Chen asked whether there is an understanding of how the Bridge Access Program has had
an effect on implementation and uptake and if there is an update on the move beyond the
Bridge Access Program and Vaccines for Adults . In addition, he asked whether there would be
more data on concomitant administration of COVID, influenza, and RSV vaccines . The lack of
data has been a barrier in trying to communicate confidence with these vaccines and trying to
accomplish administration of all of them in a single visi t.
Dr. Chatham -Stephens responded that the Bridge Access Program has been tracking these
discussions. As noted, additional lead time would help with any transition to an updated vaccine
for the next season. They are aware of this and are incorporating these discussions into their plans.
Dr. Wallace indicated that simultaneous administration is still part of general best practice.
There are no concerns with administering COVID vaccines with influenza, RSV, or other
vaccines. This is always being monitored and new information is continuously being collected.
Dr. Long thought the June decision sounded appropriate in terms of marrying it to what doctor s
anticipate now with influenza. However, it was unclear whether the vote in June would be to
recommend a universal dose for adults ≥ 65 years of age or for strain selection.
Dr. Wharton clarified that strain selection is done by FDA and the FDA’s advisory committee, VRBPAC, will be weighing in on that. T hat is not a decision that ACIP is asked to weigh in on.
The expectation is that in June, the work group will have a proposal for the committee on
proposed use of COVID- 19 vaccines in the f all. Dr. Kaslow (FDA) confirmed that the strain
selection decision would be made by FDA following the VRBPAC meeting, which is scheduled
for May 16, 2024.
Dr. Long observed that if the vote later in the afternoon was going to be for everyone ≥65 years
of age or ≥70 years of age to get the vaccine now, it has been well over 4 months since
September or October when most people got the vaccine. It seems like it would impact the cost-
effectiveness if 6 months later ACIP suggested that they all get it again. A window of 4 months
did not make sense when circulation is pretty low right now. For example, about 10% of
specimens in Philadelphia are positive for COVID -19 at this time. It was not clear why they
would make a very short -term recommendation when they would be considering a longer -term
recommendation in less than 4 months .
Dr. Wharton said that assuming that there is an updated vaccine for 2024-2025, that vaccine will
not be available until fall. That is a number of months away, even though ACIP will be
discussing it in June.
Dr. Daley expressed appreciation for Dr. Long’s call for clarification and distinction between
those. Work group members raised the issue of what happens in June 2024 in terms of who
should get the vaccine. Influenza vaccination is thought of as seasonal, with vaccination
continuing through March. The strategy for COVID is different. If someone wanted a vaccine in June and had not received a 2023-2024 vaccine, they would still be eligible and the vaccines
would not be expired. The likelihood of that happening given that they have had 9 months of
opportunity probably continues to decrease but does not go down to zero. The vote planned for
later in the day was distinctly different because it would be for now and for a group that is at
particularly high risk by virtue of age.
16

  A fresh decision will be made next year with an updated vaccine that is information by what is
learned over the past season about safety , effectiveness, barriers , and attitudes. If there is a
benefit now for people ≥65 years of age, he did not think ACIP should postpone that decision until June because it is a different decision for a different circumstance and different population. The work group was unanimous that there are many benefits to making a June decision, with
the recognition that there are some risks given unknown epidemiology, et cetera. He asked Dr. Kaslow whether, from the FDA perspective, ACIP ’s plan to make a recommendation for who
should receive a 2024-20 25 vaccine during the June ACIP meeting made sense.
Dr. Kaslow (FDA) confirmed that this does make sense.
Ms. Coyle (AIRA) acknowledged the role of health information technology systems (e.g.,
electronic health record s, pharmacy system s, immunization information system s). Some of
these codes will have to be developed, and being able to get those out and updated in systems
takes time. Therefore, it is important to build in as much time as possible for that to ensure that
as many systems as possible can make updates before vaccine administration and would be
greatly appreciated. That is, lengthening the lead time between licensure, recommendations ,
and vaccine administration would be helpful.
Vote: COVID-19 Vaccines
Although public comment was presented prior to all of the votes during this meeting, the votes
were incorporated in summary with their respective sessions for the purpose of continuity.
Dr. Megan Wallace (CDC/NCIRD) read the following proposed ACIP voting language for
COVID -19 vaccines into the record:
ACIP recommends that persons ≥65 years of age should receive an additional dose of
the 2023-2024 formula COVID -19 vaccine.
Dr. Kaslow (FDA) made a few pre-vote comments noting that: 1) O nly 40% of people over 65
years of age have received the indicated dose in the current package insert for the 2023-2024 formula. The biggest public health impact l ikely would come from increasing the number of
individuals ≥65 years of age getting that indicated dose; 2) There are suggestive data of longer
duration, particularly against the outcomes that are most important, severe disease and death,
in those who have had multiple exposures to the spike protein by infection or vaccines. In the
current context, individuals ≥65 years of age already have had multiple exposures to the spike
protein; 3) T here is a paucity of evidence for mRNA vaccines and protein -based vaccines given
at this time in the ongoing pandemic. The context of receiving an additional dose now is quite
different than it was earlier in the pandemic. As presented, pre -existing immunity is quite robust
and different than it was early in the pandemic; 4) If an antigen update is recommended this
year and is available in September, giving an additional dose of the current 2023-2024
formulation any later than June this year may not be optimal. Based on the current context and
the available data, this seems to be truly a “may ” recommendation supported by what is
basically Level 3 evidence.
17

  Motion/Vote: COVID -19 Vaccines
Dr. Kotton made a motion to approve the proposed recommendation stating, “ACIP
recommends that persons ≥65 years of age should receive an additional dose of the 2023-2024
formula COVID -19 vaccine.” Dr. Cineas seconded the motion. No COIs were declared. The
motion carried with 11 favoring, 1 opposing, and 1 abstaining. The disposition of the vote was
as follows:
11 Favored: Brooks, Beigel, Chen, Cineas, Clark, Daley, Grimes, Hance, Kotton, Loehr, Marshall
1 Opposed: Long
1 Abstained: Kaslow
Discussion Points
Members and Ex Officios were invited to make comments following the votes.
Reflecting on the COVID vaccination vote, Dr. Daley indicated that he personally would have felt
comfortable with a “should” or “may ” recommendation. While the ACIP voted for a “should”
recommendation, the points Dr. Kaslow raised do not go away and should be taken back to the
work group and discussed. The COVID Work Group had differences of opinion about where
they landed. This decision will arise for years to come, including in June. This is a reason to
pause and be humble.
CHIKUNGUNYA VACCINE
Dr. Wilbur Chen, Chair of the ACIP Chikungunya Vaccines Work Group, introduced the
chikungunya vaccines session. H e reminded the committee that the chikungunya vaccine
manufactured by Valneva was licensed in the US in November 2023. No other chikungunya
vaccine is licensed globally, and there are no existing ACIP chikungunya vaccine
recommendations. The Chikungunya Vaccines Work Group is developing policy options for
ACIP ’s consideration for use of chikungunya vaccine among US persons at risk of chikungunya,
including travelers, laboratory workers , and residents of US territories and states with risk of
transmission.
Dr. Susan Hills (CDC/NCEZID) reported that the FDA licensed the Valneva’s live attenuated
chikungunya vaccine IXCHIQ® was approved on November 9, 2023. The vaccine was approved
for individuals at increased risk of exposure to c hikungunya virus as a single dose in individuals
≥18 years of age. The vaccine is contraindicated for immunocompromised individuals and to
individuals with a history of a severe allergic reaction to any component of IXCHIQ®. Two
“Warnings and Precautions ” are listed; first, the vaccine may cause severe or prolonged
chikungunya-like adverse reactions, and second, vaccine viremia occurs in the first week
following vaccination and there are no data on the risk of vertical transmission.
18

 Dr. Hills told the committee that the vaccine was licensed through the accelerated approval
pathway. With accelerated approval, demonstration of effectiveness is based on control led
clinical trials showing the vaccine has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefits. For the chikungunya vaccine, the marker of protection was based on a neutralizing antibody titer estimated from a validated non-human primate (NHP) model. With
this approval pathway, there is a post-licensure requirement for controlled trials to confirm the
clinical benefits. The FDA has required 2 post-marketing studies. The first is a VE case -control
study in adolescents and adults ≥12 years of age. This study will be conducted in Brazil and is
planned to start by March 2026 and be completed by March 2028. The second is a pragmatic
randomized control trial (RCT) for effectiveness and safety in adults in an endemic area, w hich
is planned for initiation by October 2025 and completion by July 2029.
Dr. Hills (CDC/NCEZID) reminded the committee that c hikungunya virus is an alphavirus that is
transmitted primarily by Aedes species mosquitoes, primarily Aedes aegypti and Aedes
albopictus . Uncommon modes of chikungunya virus transmission include laboratory exposure,
intrauterine and intrapartum transmission, and bloodborne transmission through needlestick
injury. Chikungunya virus occurs in tropical and subtropical regions and periodically causes
large outbreaks throughout most parts of the world. Occasional transmission has occurred in
temperate areas. The virus periodically causes large outbreaks, with high attack rates among
one-third to three-quarters of the population affec ted.
Clinical illness is characterized by the acute onset of fever and joint pain, which is often severe and can be debilitating. Other symptoms may include headache, rash, myalgia, and/or anorexia.
In the absence of specific antiviral treatment, the approach to management typically involves
rest, fluids , and use of analgesics and antipyretics. Deaths are rare and are reported mostly in
older adults, particularly those with comorbidities, and young infants infected perinatally or by
mosquito bites . Acute symptoms of c hikungunya usually resolve in about 7 to 10 days, but
some patients have a continuation or relapse of their joint symptoms in the months after acute
illness and experience other symptoms , such as fatigue. About 50% of people have ongoing
arthralgia of variable severity for up to 3 months after infection, and about 30% may have
ongoing arthralgia for up to 12 months after infection.
Chikungunya is a reportable disease in the US, with a pproximately 100 to 200 cases reported
annually ; there is likely substantial underdiagnosis and underreporting. Infections are most
commonly acquired in Asia and the Americas , with specific locations of acquisition influenced by
local transmission patterns which vary from year -to-year. In 2023, there was a large outbreak of
chikungunya in Paraguay. Among all US travelers to destinations with risk of c hikungunya,
fewer than 1% travel to Paraguay. Among all US traveler chikungunya cases reported in 2023,
25% (20 of 80) were among persons who traveled to Paraguay.
Dr. Hills reviewed data on vaccine safety that had been reviewed by the work group.  Overall,
the work group summary of vaccine safety is that the live attenuated c hikungunya vaccine is a
reactogenic vaccine. Because safety data have only been gathered in about 3,500 subjects, it
will be important to continue to monitor vaccine safety post-licensure as the vaccine is used in
larger populations.
The work group’s assessment was that c hikungunya is a disease that can result in severe
arthralgia during the acute illness, rare serious complications, and sometimes long-term
arthralgia. The highest risk for severe outcomes is among older adults, particularly those with
comorbidities, and neonates and young infants .
19

  There is moderate disease burden among US travelers , with 100-200 cases reported annually .
There is substantially higher risk for infection if travel occurs during an outbreak . The vaccine is
immunogenic , but it also is reactogenic .
Dr. Hills presented the following draft recommendations for ACIP's consideration:
Chikungunya vaccine is recommended for persons aged ≥18 years traveling to a country or
territory where there is a chikungunya outbreak.
In addition, chikungunya vaccine may be considered for the following persons traveling to a
country or territory without an outbreak but with evidence of chikungunya virus transmission
among humans within the last 5 years:
Persons aged >65 years, particularly those with underlying medical conditions, who are
likely to have at least moderate exposure to mosquitoes OR
Persons staying for a cumulative period of 6 months or more
An outbreak will be defined as occurring when CDC posts information on an outbreak on the
CDC website. A notice will be posted as soon as CDC becomes aware of an outbreak. A similar
process is used in relation to cholera and for the cholera vaccine recommendations , with
information posted when cholera outbreaks occur.
The second part of the proposed recommendation is a shared clinical decision-making
recommendation for certain individuals traveling to an area with documented human cases .
There is more uncertainty in the risk -benefit assessment in these cases. However, there are
likely to be circumstances in which some individuals might reasonably choose vaccination or
some providers might wish to recommend it. In these circumstances, it is appropriate for there
to be a conversation between the HCP and patient about the risks and benefits, including the
likelihood of exposure based on factors such as activities, time of year, and duration of travel ;
the disease and its potential severity ; the vaccine’ s efficacy ; and the possibility of vaccine-
associated adverse events. This approach also allows the traveler ’s personal perceptions and
tolerance of risks to be taken into account.
Key risk factors for severe c hikungunya disease include older age and underlying medical
conditions (e.g., diabetes, cardiac disease, hypertension) and that key risk factors for chronic
arthralgia after chikungunya are older age and pre-existing joint problems. A key risk factor for
chikungunya virus infection among travelers is the intensity of transmission. If there is
equivalent transmission in different areas, the cumulative duration of exposure becomes important. Moderate exposure could include travelers who might have at least 2 weeks of
cumulative exposure to mosquitoes in indoor or outdoor settings . This does not include travelers
who might have limited exposure to mosquitoes (e.g., those traveling for business and likely to
be mainly in mosquito-protected indoor settings ).
Dr. Hills noted that when the work group was developing the recommendation options for ACIP ’s consideration, they aimed to develop recommendations that balance the desirable and
undesirable effects of vaccination based on consideration of all of the disease and vaccine
factors. The “recommended” component of the recommendations aims to target the travelers
with highest risk, where the benefits of receiving the vaccine almost certainly outweigh the risks. The “may be considered” recommendation aims to include groups with higher risk where the
work group did not think a specific  recommendation was justified because there is more uncertainty in the risk -benefit assessment, but for which some individuals might reasonably
choose vaccination, some providers might reasonably wish to recommend it, and a discussion
20

  and decision-making based on a conversation between the provider and patient would be valuable.
Dr. Kotton asked whether there were any thoughts about an upper age limit by which this
vaccine no longer would be given. Her concern regarded safety among non-
immunocompromised people in their 70s and 80s.
Dr. Hills shared some data to help provide some context to this. Data for arthralgia by age group
do not show that frequency and maximum severity increase with age. While there are few data, frequency of any particular adverse event ( AE) is similar or lower in older age groups.
Dr. Daley made a motion to approve the draft recommendation language as presented, which Dr. Long seconded.
Dr. Kotton noted that while it did not necessarily have to be in the vote language, it should be
non-immunocompromised persons ≥18 years of age. Dr. Hills indicated that this is clearly
indicated in the top right corner of the package insert and will be included in the MMWR .
Dr. Cineas asked whether there were any data b eyond 1 year in terms of how durable the
vaccine is for people who might be traveling multiple times to endemic or areas where there is
an outbreak .
Dr. Hills indicated that the work group reviewed data for 2 years and found that seroresponse
rates are very high at 2 years. The manufacturer is planning to continue to monitor for at least 5
years.
Dr. Hills indicated that the plan is to create a table to accompany the recommendations that
describes the various risk factors for chikungunya and risk of chikungunya virus infection. The
work group preferred to leave the proposed recommendation language fairly straightforward,
and provide the table to facilitate provider/patient discussions .
Dr. Hills next presented the proposed policy options for chikungunya vaccine use among
laboratory workers . At least 44 cases of chikungunya virus infection among laboratory workers
have been reported worldwide during the last 50 years. Of these, 43 cases were overt disease,
1 was an asymptomatic infection, and there were no deaths. Among US laboratorians , 4
disease cases have been reported in the 8-year period since chikungunya became a nationally
notifiable disease in the US in 2015. Documented routes of transmission of chikungunya virus in
the laboratory have been through the aerosol route and the percutaneous routes. Among cases
of percutaneous transmission with more detailed information available, 2 researchers
experienced a needlestick injury while they were working with and injecting mice. For the third
case, a researcher experienced a forceps prick while dissecting mosquitoes infected with
chikungunya virus. Although not documented, transmission through accidental mucosal
exposure is also possible.
21

 Factors the work group considered regarding recommendations for laboratory workers were that
vaccination is required for only limited number of staff who might be exposed to live
chikungunya virus . Vaccination is not necessary for workers handling routine clinical samples
who should be consistently using standard practices for handling patient samples. Therefore,
recommendations are only for laboratorians undertaking research or very specific diagnostic
work using live virus (e.g., plaque reduction neutrali zation tests ). The work group surmised that
the benefits of vaccination outweigh risks for small group of laboratorians working with live virus, given potential for acquiring chikungunya virus infection which can result in severe
polyarthralgia and possibly chronic arthralgia. The work group proposed the following draft
recommendation for ACIP consideration:
Chikungunya vaccination is recommended for laboratory workers with a potential for exposure to chikungunya virus.
The recommendations would be accompanied by clear information for implementation, including
noting that a local institutional biosafety committees should undertake a risk assessment of the
potential for exposure to chikungunya virus for each laboratory worker working with the virus, considering the type of work to be performed and the biosafety level at which work will be
conducted; vaccination is not necessary for workers handling routine clinical samples.
Dr. Loehr made a motion to accept the proposed recommendation as written. Dr. Cineas
seconded the motion.
Dr. Hills presented clinical guidance for use of live attenuated chikungunya vaccine in pregnant
and breastfeeding individuals.  The spectrum of illness of chikungunya in pregnant persons
appears to be similar to that among non-pregnant persons . Adverse outcomes such as fetal
loss, stillbirth, or preterm birth as a result of vertical transmission have been documented but
are rare. However, infection commonly results in adverse neonatal outcomes if pregnant
individuals are infected around the time of deliver y. In these cases, intrapartum transmission
occurs in about 30% to 50% of cases. When infection occurs following intrapartum transmission,
severe and sometimes fatal illness can result. Clinical presentation in the newborn is commonly
with encephalopathy , sepsis-like illness , cardiac, dermatologic , and hemorrhagic manifestations.
In the setting of neonatal infection, n eurocognitive outcomes are often poor, particularly if the
initial clinical presentation is with encephalopathy. Young infants infected by mosquito -borne
transmission are also at risk for severe disease, particularly during the first few months of life.
Clinical presentations in young infants are similar to presentations in infected neonates. This
issue is important because of its relevance to possible protection of young infants by transplacental transfer of antibodies after maternal vaccination, although this is theoretical.
The data are insufficient to determine whether there are any safety risks in vaccination during
pregnancy , given that pregnancy was an exclusion criterion in the clinical trials and only 2
pregnant persons were inadvertently vaccinated. Both of the 2 women were vaccinated during
the first trimester. One was a 36-year -old who experienced a spontaneous abortion 59 days
after vaccination at a gestational age of about 10 to 14 weeks. The other was a 23-year -old who
had anembryonic pregnancy noted 53 days after vaccination and experienced a spontaneous
abortion at 55 days at about 8 weeks gestation. It is important to note that anembryonic
pregnancies generally result from a chromosomal problem at conception. An estimated 20% to
25% of all pregnancies lead to pregnancy loss , with the highest rates in the first trimester and
increasing rates with increasing maternal age.
22

  Vaccine viremia occurs in the first week following administration of c hikungunya vaccine, and it
is not known if the vaccine virus can be vertically transmitted and cause fetal or neonatal
adverse reactions. Under “Use in Specific Populations,” the package insert notes that a decision
to administer chikungunya vaccine during pregnancy should take into consideration the
individual's risk of wild -type chikungunya virus infection, gestational age, and risks to the fetus
or neonate from vertical transmission of wild-type chikungunya virus. It notes that if neonates
are born within 14 days of their mother receiving chikungunya vaccine, they should be closely
monitored after birth for potential disease due to vaccine virus.
In the future, the work group will be considering recommendations for persons in US territories
and states with risk of chikungunya virus transmission. Therefore, the vaccine potentially could
be used in a larger population of pregnant individuals in future than is anticipated with its use
among travelers and laboratory workers in the near -term. Having considered the issues around
risks of chikungunya disease for pregnant individuals and their infants and vaccine use in
pregnancy, the objectives of chikungunya vaccination during pregnancy are to protect the
pregnant person from chikungunya virus infection and avoid maternal infection around the time
of delivery to prevent intrapartum virus transmission and severe disease in the newborn. In
addition, transplacental transfer of antibodies might also protect young infants from mosquito-
borne transmission and severe disease.
The following is the work group’s proposed clinical guidance language for use of chikungunya
vaccine in pregnant individuals :
Pregnant individuals should avoid the risk for chikungunya virus infection, if possible (e.g.,
by avoiding travel to an area with virus transmission, particularly during an outbreak).
Pregnancy is a precaution for vaccination with a live attenuated chikungunya vaccine. In
general, vaccination should be deferred until after delivery. However, when the risk of infection is high and exposure cannot be avoided, a healthcare provider should discuss with
a pregnant person the potential risks of chikungunya virus infection and the potential
benefits and risks of vaccination so that vaccination can be considered.
If pregnant persons choose to be vaccinated, out of caution vaccination should genuinely be avoided during the 1
st trimester (until 14 weeks) gestation and after the 36th week of
gestation.
− Avoiding vaccination during the first trimester is preferred for two reasons. Firstly, pregnancy loss has been reported in two individuals vaccinated during the first
trimester, although one was an anembryonic pregnancy. In addition, the vaccine is
reactogenic and can cause fever , and fever has been linked to birth defects in the 1
st
trimester.
− Avoidance of vaccination after the 36th week of gestation is to limit the risk of vaccine-
induced viremia occurring in the intrapartum period, and thus to reduce the theoretical risk for perinatal transmission and potential adverse outcomes.*
*Vaccine viremia is considered to occur in most individuals in the first few days after vaccination and to decrease thereafte r;
viremia was no longer detectable in any clinical trial subjects at 14 days after vaccination.
In line with common practice following vaccination with live vaccines, non-pregnant vaccine recipients should generally wait 4 weeks before becoming pregnant. If a pregnant person is inadvertently vaccinated outside of the preferred period or becomes pregnant within 4
23

 weeks after the chikungunya vaccination, this should not be considered a reason to
terminate the pregnancy.
This guidance is intended to maximize the benefits of vaccination while minimizing risks associated with vaccination during pregnancy.
Chikungunya viral ribonucleic acid ( RNA ) has been detected in breast milk of women in
endemic areas on very rare occasions. No studies have reported detection of replicating virus.
Although the data are limited, chikungunya virus transmission through breastfeeding has not
been reported. No human data are available on whether chikungunya vaccine virus or
antibodies are present in breast milk after vaccination. It is known in general that neonates and other infants less than 1 year of age are at risk for severe disease, particularly in the first few
months of life, if infected with wild-type chikungunya virus. The vaccine virus is attenuated, but
there are no data on potential outcomes for an infant if c hikungunya vaccine virus was
transmitted by breastfeeding.
In the package insert for the vaccine, breastfeeding is neither a contraindication nor precaution
for vaccination. The language in the package insert notes that the developmental and health
benefits of breastfeeding should be considered, along with the mother ’s clinical need for the
vaccine and any potential adverse effects on the breastfed child from the vaccine or from the
mother’ s susceptibility to c hikungunya. The package insert also notes that vaccine viremia
occurs after vaccination, but that any potential for transmission of the vaccine virus from mother
to infant through breast milk is unknown.
The following is the work group’s proposed clinical guidance language for use of chikungunya
vaccine in breastfeeding individuals:
Breastfeeding individuals and their infants should avoid the risk for chikungunya virus
infection, if possible (e.g., by avoiding travel to an area with transmission particularly during
an outbreak).
In the absence of data, breastfeeding is a precaution for vaccination. When the risk of
infection is high (e.g., during an outbreak) and exposure cannot be avoided, a health care provider should discuss with a breastfeeding individual the developmental and health
benefits of breastfeeding for the infant, the risks of chikungunya virus infection, and the
potential benefits and risks of vaccination, and offer the vaccine to the breastfeeding person.
At the current time, the data are insufficient to make a recommendation to defer breastfeeding for any period after vaccination.
Dr. Riley , liaison representative from the American College of Obstetricians and Gynecologists
(ACOG), expressed ACOG’s support for the use of the c hikungunya vaccine in pregnancy as a
precaution when infection risk is high and exposure cannot be avoided using shared clinical
decision-making. When chikungunya infection occurs around the time of delivery, it frequently
results in antepartum transmission t hat in and of itself results in severe outcomes for neonates.
Vaccination during pregnancy, particularly around the time of delivery or ≤36 weeks  gestation,
could protect the mother and the fetus. It is also possible that transplacental transfer of
antibodies occurs and could protect young infants from mosquito-borne transmission. With the
observed severe outcomes when a pregnant individual gets infected around the time of delivery, any opportunity to protect a pregnant person before the antepartum period is beneficial.
24

  While some live attenuated vaccines are contraindicated during pregnancy, other vaccines such
as dengue, Ebola, and yellow fever have been licensed with pregnancy as a precaution.
Therefore, in an outbreak situation or other time when infection risk is quite high, ACOG
supports the use of this vaccine during pregnancy to prevent the chances of a pregnant person acquiring the infection around the time of delivery.
Dr. Long said she was struck that there are no data on giving this vaccine to pregnant women, but they do not want to disenfranchise them from being immunized. She recalled the two
inadvertently administered vaccines in the first trimester, both of which had adverse outcomes.
Dr. Dana Meaney -Delman, CDC, indicated that one was an anembryonic pregnancy that likely
was chromosomal in nature and unlikely biologically plausible to be related to the vaccine. While
they may never know more about those two pregnancies, the pregnancy losses occurred more
than 50 days out from vaccination, which also makes it unlikely.
Although public comment was presented prior to the votes during this meeting, the votes were
incorporated in this summary with their respective sessions for the purpose of continuity.
Vote #1: Chikungunya Vaccines for Travelers
Dr. Susan Hills (CDC/NCEZID) read the following proposed ACIP voting language into the
record for c hikungunya vaccines pertaining to travelers:
Chikungunya vaccine is recommended for persons aged ≥18 years traveling to a country
or territory where there is a chikungunya outbreak.
In addition, chikungunya vaccine may be considered for the following persons traveling
to a country or territory without an outbreak but with evidence of chikungunya virus
transmission among humans within the last 5 years:
─ Persons aged >65 years, particularly those with underlying medical conditions, who are likely to have at least moderate exposure to mosquitoes, OR
─ Persons staying for a cumulative period of 6 months or more.
25
Motion/Vote #1: Chikungunya Vaccines for Travelers

  Dr. Daley made a motion to approve the proposed Vote #1 recommendation for chikungunya
vaccines stating, “ Chikungunya vaccine is recommended for persons aged ≥18 years traveling
to a country or territory where there is a chikungunya outbreak. In addition, chikungunya vaccine
may be considered for the following persons traveling to a country or territory without an outbreak but with evidence of chikungunya virus transmission among humans within the last 5
years: Persons aged >65 years, particularly those with underlying medical conditions, who are
likely to have at least moderate exposure to mosquitoes, OR Persons staying for a cumulative period of 6 months or more.” Dr. Long seconded the motion. No COIs were declared. The
motion carried with 12 favoring, 0 opposing, and 1 abstaining. The disposition of the vote was
as follows:
12 Favored: Brooks, Beigel, Chen, Cineas, Clark, Daley, Grimes, Hance, Kotton, Loehr,
Long, Marshall
0 Opposed: N/A
1 Abstained: Kaslow
Vote #2: Chikungunya Vaccines for Laboratory Workers
Dr. Hills read the following proposed ACIP voting language into the record for chikungunya vaccines pertaining to laboratory workers:
Chikungunya vaccination is recommended for laboratory workers with potential for
exposure to chikungunya virus.
Motion/Vote #2: Chikungunya Vaccines for Travelers
Dr. Loehr made a motion to approve the proposed Vote #2 recommendation for chikungunya
vaccines stating, “Chikungunya vaccination is recommended for laboratory workers with
potential for exposure to chikungunya virus.” Dr. Cineas seconded the motion. No COIs were
declared. The motion carried with 13 favoring, 0 opposing, and 0 abstaining. The disposition of
the vote was as follows:
13 Favored: Brooks, Beigel, Chen, Cineas, Clark, Daley, Grimes, Hance, Kaslow, Kotton,
Loehr, Long, Marshall
0 Opposed: N/A
0 Abstained: N/A
Members and Ex Officios were invited to make comments following the votes. Dr. Chen noted
that while the chikungunya vaccine was first licensed in the US, the burden of disease is global.
He expressed his hope that the discussions they had throughout the day would not negatively affect the consequences of implementation of the vaccine globally. He would like to continue to
see additional vaccines for other mosquito-borne agents in the US and around the world.
26

 DIPHTHERIA AND TETANUS TOXOID (DT) VACCINE
Dr. Michele Hughes (CDC/NCIRD) provided an update on CDC’ s guidance for Td vaccines for
young children. As part of the routine vaccination schedule, CDC recommends a primary series
of the pediatric diphtheria-, tetanus -, and pertussis -containing vaccines (DTaP ) vaccines for
children <7 years of age. For children<7 years of age who developed a contraindication to
pertussis -containing vaccines, CDC previously recommended the pediatric diphtheria and
tetanus toxoid vaccine (DT) instead of DTaP. Recently, the s ole DT vaccine manufacturer in the
US discontinued DT production. The last available lot expired in April 2023. There is no longer
DT vaccine available in the US.
The only contraindication specific to the pertussis component in DTa P is encephalopathy within
7 days of vaccination that is not attributed to another cause. While the exact numbers are not
known, the occurrence of this AE is extremely rare. In light of DT no longer being an available
option, CDC issued the following updated vaccination guidance for the use of Td in young
children with a contraindication to pertussis -containing vaccines :
CDC recommends young children receive DTaP as the first dose in the diphtheria, tetanus,
and pertussis childhood vaccination series.
CDC recommends continued use of DTaP unless a contraindication to pertussis -containing
vaccines develops.
For young children who develop a contraindication to pertussis -containing vaccines, vaccine
providers may administer Td for all recommended remaining doses in place of DTaP.
The impact on diphtheria protection is uncertain. Td is a tetanus - and diphtheria toxoid-only
formulation licensed only for ages ≥7 and older . The use of Td in this situation would be an off-
label use. Td contains a lower dose of diphtheria toxoid compared to DT and the impact of this
lower dose on the protection provided against diphtheria in young children is uncertain. There
are no available data evaluating the effectiveness of Td against diphtheria when used as part of
the primary series in young childr en.  Children may have less protection against diphtheria and
no additional protection against pertussis if they receive Td instead of DTaP. CDC has posted
this guidance on its website at www.cdc.gov/vaccines/vpd/dtap-tdap-td/hcp/td-offlabel.html . In
order to be covered by VFC for children < 7 years of age, a minor update is needed.
Dr. Jeanne Santoli (CDC/NCIRD) gave an update on the current Td supply and the proposed
VFC updates. As noted, MassBiologics has discontinued production of their Td vaccine,
TdVax ™. Grifols, who is the exclusive distributor for TdVax ™, expects to have product available
through approximately June 2024. Sanofi, who manufacturers Tenivac®, the only other US-
licensed Td vaccine, is taking steps to augment their available supply of Td for the US.
However, it is anticipated that the supply of Td vaccine in the US market will be constrained during 2024. Temporary ordering controls have been put into place in the public and private sectors to help manage the gap in supply. Adult formulation tetanus and diphtheria toxoids and
acellular pertussis vaccine ( Tdap) is available from both US -licensed manufacturers without
supply constraints at this time. Based on the rarity of developing a contraindication to pertussis -
containing vaccines, the temporarily constrained supply of Td vaccine is not anticipated to prevent providers from utilizing Td vaccine for these children in the VFC program.
27

  Dr. Santoli indicated that the purpose of this resolution was to: 1) add Td vaccine for use in
children <7 years of age for whom receipt of the pertussis component is contraindicated; and 2)
update the language regarding the Tdap booster to align with ACIP recommendations. Eligible
groups include c hildren and adolescents aged 6 weeks through 18 years , which was
unchanged.
Because Td is not currently included in the VFC program, the proposed language to add it to the
VFC resolution is as follows:
Approve the Vaccines for Children (VFC) resolution for diphtheria, tetanus, and pertussis
vaccines.
Dr. Long noted that with anticipation that Td is frequently not stocked in places like emergency
departments anymore, there already is language in the R ed Book stating that Tdap can be used
if there is no Td.
Dr. Santoli indicated that in terms of the VFC Resolution, Tdap is absolutely covered for persons >7 years of age. It is not covered for the persons <7 years of age.
In terms of the recommendation, Dr. Hughes added that ACIP's previous recommendation that
Tdap can be used in lieu of Td would remain.
Dr. Long made a motion to accept the proposed wording for a vote, which Dr. Kotton seconded.
Vote: VFC Resolution for Diphtheria, Tetanus, and Pertussis Vaccines
While public comment was presented prior to the votes, the votes were combined in this summary with their respective sessions for the purpose of continuity.
Approve the Vaccines for Children (VFC) Resolution for diphtheria, tetanus, and
pertussis vaccines.
Motion/Vote: VFC Resolution for Diphtheria, Tetanus, and Pertussis Vaccines
Dr. Long made a motion to approve the proposed recommendation for the VFC Resolution stating, “Approve the Vaccines for Children (VFC) Resolution for diphtheria, tetanus, and
pertussis vaccines.” Dr. Kotton seconded the motion. Dr. Chen declared a COI due to his active collaboration with MassBiologics, the maker of a DT vaccine. The motion carried with 12 favoring, 0 opposing, 0 abstaining, and 1 recusing. The disposition of the vote was as follows:
12 Favored: Brooks, Beigel, Cineas, Clark, Daley, Grimes, Hance, Kaslow, Kotton, Loehr,
Long, Marshall
0 Opposed: N/A
0 Abstained: N/A
1 Recused: Chen
28

  INFLUENZA VACCINES
The influenza session was opened by Dr. Jamie Loehr , ACIP Influenza Vaccine Work Group
Chair.
Dr. Aaron Frutos (CDC/NCIRD/ID) presented CDC’s interim estimates of 2023/2024 seasonal
influenza VE. This year, 4 networks contributed to the interim estimates of VE against
laboratory -confirmed influenza for children, adolescents , and adults in the out-patient and in-
patient settings.
The methods used by each network to estimate influenza VE are very similar. All enrollees
across all networks sought medical care for acute respiratory illness (ARI). Patients are included
from fall 2023 to early 2024. Each network uses a test-negative design, which compares the
vaccination odds among case patients with influenza confirmed by molecular assay versus
control patients testing negative for influenza and SARS -CoV-2. Vaccination status was
determined as the receipt of any of the 2023-2024 seasonal influenza vaccines according to medical records, immunization registries, claims data, and/or self-report. VE estimates were calculated for influenza A subtypes A (H1N1 )pdm09 and A (H3N2 ) when possible. VE was not
estimated for some age groups and settings when the sample size was small or when models
did not converge.
Pediatric VE against any influenza ranged from 59% to 67% in out-patient settings and 52% to
61% in the in-patient setting. VE estimates were consistent across networks. Pediatric VE
against influenza A ranged from 46% to 59% in out-patient settings and 46% to 56% in the in-
patient setting. Pediatric VE against influenza A (H1N1 )pdm09 ranged from 54% to 61% in out-
patient settings and was 60% in the in-patient setting. Pediatric VE against influenza A(H3N2 )
was 55% in out-patient settings and was not estimated in the in-patient setting. Pediatric V E
against influenza B ranged from 64% to 89% in out-patient settings and was not estimated in
the in-patient setting.
For adults ≥18 years and older , vaccination prevalence ranged from 39% to 52% among test-
negative controls across settings. Adult VE against any influenza ranged from 33% to 49% in
the out-patient settings and 41% to 44% in the in- patient setting. Adult VE against influenza A
ranged from 27% to 46% in out-patient settings and 40% to 42% in the in-patient setting. Adult
VE against influenza A( H1N1 )pdm09 was 25% in out-patient settings and 50% in the in-patient
setting. Adult VE against influenza A( H3N2 ) was 54% in the out-patient setting and was not
estimated in the in-patient setting. Adult VE against influenza B was 78% in out-patient settings
in 2 networks and 60% in the in-patient setting. Again, consistent results were observed across
networks. Among adults ≥65 years of age, the prevalence of vaccination among test-negative controls
ranged from 48% to 68% across settings. VE against any influenza ranged from 41% to 51% in
out-patient settings and was 42% in 2 networks in the in-patient setting. Among adults ≥65
years of age, VE against influenza A ranged from 40% to 52% in out-patient settings and 42%
to 47% in the in-patient setting. VE against influenza B for adults ≥65 years of age was 69% in
out-patient settings and was not estimated in the in-patient setting.
29

 These estimates showed that vaccination with the 2023-2024 influenza vaccine reduced the risk
for medically -attended influenza out -patient visits and hospitalizations among children,
adolescents, and adults across 22 US states. Vaccination was effective against both influenza
A, mostly subtype A(H1N1)pdm09, and B Victoria viruses that have circulated this season.
Dr. Sophie Zhu (California Department of Public Health and CDC/PHIC/DWD) presented i nterim
influenza VE a gainst laboratory -confirmed influenza in California for October 2023—January
2024. New public health data reporting requirements in California offer an opportunity to
calculate VE against laboratory -confirmed influenza, resulting in estimates that are available
ahead of traditional platforms. As of January 1, 2023, all influenza vaccination records became
reportable to the California Immunization Registry (CAIR). P ositive influenza results have been
reportable in California since October 2019. Negative influenza results became reportable a s of
June 15, 2023 to the California Reportable Disease Information Exchange (CalREDIE ), the
state electronic communicable disease reporting system .
For this analysis, influenza laboratory results were matched to immunization registry data to
calculate early VE estimates against laboratory -confirmed influenza in California during the
2023-2024 influenza season. The estimates from this analysis reflect VE against l aboratory -
confirmed influenza using nucleic acid amplification tests and include persons tested for
influenza from diverse care settings and symptom severity levels. VE is calculated using a case-
control design in which persons testing positive for influenza are case patients and persons
testing negative for influenza are control patients.
Persons included in the analysis were all California residents ≥6 months of age with molecular
tests for influenza A or B captured by the s tate electronic laboratory reporting system. Most
influenza testing performed at clinical and commercial laboratories that report influenza A and B
test results do not perform subtyping. The dates of this analysis were October 1, 2023, through
January 31, 2024. Participants were considered vaccinated if there was at least 1 dose of
seasonal influenza vaccine documented i n CAIR ≥ 14 days before testing. Adjusted VE was
calculated as VE = (1 – adjusted odds ratio) x 100% . A m ixed-effects logistic regression model
was used that was adjusted for age, ethnicity, testing week (random effect), and county (random
effect).
In California, overall influenza virus positivity the week of February 19, 2024, was 6.5% and had
declined from prior weeks. Based on subtyping at public health laboratories in California, this is
a predominantly H1 season so far. Of the samples, 82% have been influenza A and 75% have
been H1. A total of 678,422 individuals were included in this analysis. This included 77,501
influenza-positive cases , which is about 11% positivity , and 600,921 influenza-negative control
patients. The median age was 31 years for case patients and 44 years for control patients.
There was a similar breakdown of race and ethnicity for the case and control patients. Overall,
28% of individuals were vaccinated and 18% of case patients were vaccinated overall versus
29% of controls. Vaccination increased month-by -month from 13% during October to 34%
during April. A similar lower vaccination rate was seen in case versus control patients
throughout all time periods.
Adjusted VE against laboratory -confirmed influenza overall was 45%. VE declined with
increasing age and was highest at 56% in children ≤ 18 years of age, 48% in adults 18─ 49 years
of age, 36% in adults 50 ─64 years of age, and lowest at 30% in adults ≥65 years of age. VE
against influenza A was lower than overall influenza VE, but was still protective at 42%. Over
90% of cases in this analysis were influenza A, which is consistent with both California and
national trends.
30

    Age-specific VE declined with increasing age and was lowest for adults ≥65 years of age at
29%. VE for influenza B was high at 76% . Estimates were generally comparable across younger
age groups, ranging from 75% to 79% for persons 6 months ─49 years of age. Similar to
influenza A, estimates were lower among adults ≥50 years of age. Less than 10% of cases were
influenza B.
Mandatory public health data can be leveraged to calculate timely in-season influenza VE as an
additional estimate supporting existing public health influenza prevention efforts. Earlier
estimates can inform public health action and messaging for additional prevention measures
prior to the peak of influenza infections and could be especially informative for healthcare
settings that may need to reallocate resources to prepare for increased hospital capacity.
C. Buddy Creech, MD, MPH (Vanderbilt University Medical Center) presented on the safety of
quadrivalent live attenuated influenza vaccine ( LAIV4) in children with asthma. In this study, 151
children and adolescents 5–17 years of age with persistent asthma were randomized to LAIV (n
= 79) or quadrivalent inactivated influenza vaccine ( IIV4) (n = 72). The primary objective was to
compare the proportion of participants who experienced asthma exacerbation during the 6
weeks after LAIV4 versus IIV4. Persistent asthma was defined as provider diagnosis of asthma
plus prescription of a long-acting controller medication and an asthma exacerbation was defined
as an acute episode of progressively worsening shortness of breath, cough, wheezing, chest
tightness , or respiratory distress for which the patient sought medical attention or received a
new prescription for systemic corticosteroids.
LAIV4 was not associated with increased asthma symptoms or asthma exacerbations in the 14-or 42-day windows following immunization. Rates of reactogenicity were similar between the 2
groups, although myalgia and sore throat were more common in the IIV 4 arm. LAIV4 may be a
suitable option for children ≥5 years of age who have asthma, including those with moderate to
severe asthma.
Dr. Lisa Grohskopf (CDC/NCIRD/ID) provided an update on influenza B/Yamagata surveillance.
Up until the late 1970s, the number of viruses in influenza vaccines varied from year -to-year.
There was variability in the formulation from year -to-year, starting around the 1978-1979
season. C onsistent seasonal vaccination has been available with trivalent vaccines with an
A/H1 , A/H3, and 1 B virus. During the 1980s, there was an appreciation that there were 2
lineages of influenza B viruses for which research evidence suggested that there was not
optimal cross -immunity. There was only one B lineage in the vaccine, so one of the two had to
be selected for inclusion in the vaccine. Q uadrivalent influenza vaccines became available in
the market in 2013-2014 and c ontained 2 B viruses, 1 from each lineage. After the 2013-2014
season, there was a gradual phase-in of the quadrivalent influenza vaccines . Some
manufacturers went from one season to the next from trivalent to quadrivalent. Some phased
them in within their brand over time. The transitioned to quadrivalent influenza vaccines was
largely complete before the 2021-2022 season, with only 1 lot of trivalent released that season.
There have now been a couple of seasons with only quadrivalent vaccines.
As Dr. Kondor presented during the October 2023 meeting, there have been no confirmed
naturally occurring influenza B/Yamagata viruses in global surveillance since March 2020. The
LAIV contains B/Yamagata, so it is conceivable that this might be seen in surveillance.
However, there have been no wild-type detections of naturally occurring B/Yamagata viruses .
During the Fall 2023 discussions for Southern Hemisphere influenza vaccine composition, WHO
and FDA concluded that coverage of influenza B/Yamagata was no longer warranted and
should be removed from vaccines as soon as feasible.
31

  Since then, WHO met and made recommendations for the N orthern Hemisphere for the 2024-
2025 season that include a second B virus for those countries that elect to use/ market a
quadrivalent vaccine. Decisions regarding the composition are made by individual national
regulatory authorities. For the US, that is the FDA. The FDA is set to discuss composition of
2024-2025 US influenza vaccines on March 5, 2024.
Ms. Rebecca Coyle (AIRA) pointed out that the codes for trivalent vaccine have been
inactivated because they have not been used in the last several seasons. For any upcoming
decisions, particularly by manufacturers that will be moving to trivalent influenza vaccine as
soon as this year, it will be to be important to have conversations as soon as possible about
reactivating the old codes versus trying to create new codes. There is a relatively short period of
time between now and the next influenza season, so the time is now to make sure the codes are correct for billing to make this as seamless as possible.
POLIO VACCINE
Dr. Oliver Brooks, chair of the ACIP Polio Vaccine Work Group, introduced the polio vaccine
session.
Dr. Sarah Kidd (CDC/NCIRD) reminded the committee that paralytic disease occurs in < 1% of
poliovirus infections and approximately 75% of infections are asymptomatic. There are 3
poliovirus serotypes with different epidemiological and clinical characteristics and immunity to
one serotype does not result in significant immunity to other serotypes. The ratio of paralytic
cases to infections varies by serotype, ranging from approximately 1 in 190 infections for T ype 1
to approximately 1 in 1,900 infections for Type 2. Poliovirus is considered highly infectious and
is spread through the fecal -oral or or al-oral routes. Fecal -oral transmission is considered the
most important pathway, particularly in settings with suboptimal hygiene and sanitation. Virus
may be present in the stool of infected persons for up to 6 weeks and sometimes longer.
Individuals who are asymptomatic can still shed virus and transmit it to others.
Inactivated polio vaccine (IPV) is the only polio vaccine that has been used in the US since
2000. It contains inactivated poliovirus Types 1, 2, and 3. It cannot replicate, infect, or cause
disease. It induces effective humoral immunity and prevents paralysis. It also induces some
nasopharyngeal mucosal immunity but does not provide substantial intestinal immunity or
prevent gastrointestinal shedding.
Oral polio vaccine (OPV ) is no longer used in the US. It is a live-attenuated vaccine that can
come in different formulations. Trivalent vaccine (tOPV) c ontains poliovirus Types 1, 2, and 3.
Bivalent vaccine (bOPV ) contains Types 1 and 3 poliovirus. Monovalent OPV (m OPV ) contains
just a single serotype. OPV replicates in the gut and is shed in the stool . It induces both humoral
and mucosal immunity , so that it prevents paralysis and transmission of poliovirus. For this
reason, it has been considered the historical vaccine of choice for countries experiencing polio
outbreaks. However, the attenuated vaccine virus can revert to a neurovirulent form that causes paralysis. nOPV2 is a next-generation version of the Sabin Type 2 mOPV that was designed to
be more genetically stable and less likely to revert to a neurovirulent form. Between March 2021 and December 2023, almost a billion doses were administered as part of outbreak responses in
35 countries under a WHO Emergency Use Listing (EUL) approval. As of December 2023, it
earned WHO prequalification status.
32

 In the US, the incidence of paralytic polio decreased rapidly after the introduction of the Salk
IPV in 1955. The Sabin OPV was used for routine childhood immunization for decades , but an
enhanced potency IPV was introduced in 1997 as part of a sequential schedule with OPV. In
2000, the US moved to an IPV-only schedule. IPV has been the only polio vaccine
recommended in the US since that time. Wild poliovirus type 1 (WPV1) and vaccine- derived
polioviruses are still circulating in certain parts of the world. Approximately 450 paralytic polio
cases caused by WPV1 and circulating vaccine- derived polioviruses (cVDPV) that have been
identified in the last 12 months .
A case of paralytic polio caused by VDPV T ype 2 (VDPV2) was confirmed in an unvaccinated
young adult from Rockland County, New York on July 21, 2022. Genetic sequencing has indicated a linkage between this case to polioviruses collected in wastewater in Israel , the UK ,
and Canada. Of note, Rockland County has reported overall low vaccine coverage for over 20
years. When this case was identified in s ummer 2022, only 60% of children under 2 years of
age had received 3 doses of IPV . ZIP Code level coverage in the area was as low as 37% in
some areas. Fortunately, no additional paralytic cases were identified.
Poliovirus related to the case was detected in wastewater in several New York State (NYS)
counties and in New York City (NYC) . Retrospective testing detected poliovirus in the area as
early as April 2022, indicating circulation and asymptomatic infections in the area since at least
that time. Related virus continued to be consistently detected in wastewater until the beginning
of November 2022. The most recent detection was February 22, 2023, in Rockland County.
Samples collected in the last year have all been negative.
The primary vaccination response to the 2022 outbreak was focused on identifying under -
vaccinated and unvaccinated persons and providing catch-up vaccination with IPV. However, in
fall 2022 when there were still wastewater detections of poliovirus, it was unclear whether the
strategy was going to be sufficient to interrupt circulation. WHO recommendations for polio
outbreaks in countries like the US with exclusive IPV vaccination and high sanitation and
hygiene are to conduct a timely outbreak response with IPV only if poliovirus transmission is
confined in a well -defined population group or geographic area. However, if transmission
persists, WHO recommends considering an OPV response. Therefore, the work group was
asked to discuss considerations for the potential use of nOPV2 as an outbreak response
measure in the US.
Given that the New York outbreak had already waned at the time of the work group discussions,
the question the work group took up was a theoretical one, “S hould nOPV2 be used in
combination with a catch -up IPV campaign during a future Type 2 poliovirus outbreak in the
US?” The population under consideration would be persons living in an area with circulating
poliovirus. The intervention would be nOPV2 vaccination for the general population in addition
to catch-up IPV vaccination for un- or under -vaccinated persons. That would be compared to
the intervention of catch- up IPV vaccination only. The outcomes of interest were prevention of
paralytic poliomyelitis; the extent and duration of poliovirus circulation in the community ; serious
adverse events , including vaccine-associated paralytic polio; and possible introduction of a new
VDPV2.
The work group used the ACIP EtR F ramework and domains to frame their discussions. Based
on the information presented, the work group had previously agreed that polio is a problem of
public health importance. For potential benefits and harms, the work group noted that there are
high rates of seroconversion following 1 and 2 doses of nOPV2 when administered to infants.
33

  Given that vaccination with IPV is already recommended in this country, the main benefit of
nOPV2 would be to confer gastrointestinal immunity.
Sabin OPV2 reduces the odds of fecal shedding following a subsequent oral challenge dose by
more than 90% compared to no vaccination. There are no direct data for nOPV2, but it has
performed as expected in the field in terms of slowing or stopping outbreaks. A small Phase 1
study among adults showed evidence of gastrointestinal immune response following nOPV2
administration. It is known that nOPV2 is a live virus and it is shed in stool by nOPV2 recipients
following vaccination. When measured by PCR, 85% had detectable vaccine virus in stool at 7
days . This decreased to 40% to 57% by 28 days. When measured by culture, which is probably
a better measure of infectious virus, 40% were shedding at 7 days . This decreased to 1% to
14% by 28 days.
nOPV2 was developed to be more genetically stable than Sabin OPV2 and less likely to regain
neurovirulence in the laboratory . However, there is still a risk of vaccine- associated paralytic
polio (VAPP) in recipients. The estimated risk of VAPP for nOPV2 is estimated to be 0.07 cases
per million recipients or 1 case per 14.3 million recipients. This is compared to Sabin OPV with
an estimated case rate of 0.25 to 4 cases per million recipients or 1 per 0.25 million to 4 million
recipients. The risk of VAPP is known to be highest in previously unimmunized children who are
receiving their first dose of OPV or in immunocompromised patients. And the risk of VAPP could
be mitigated by limiting nOPV2 administration to persons who had previously received at least 1
dose of IPV. It also is known that there is a risk of ongoing transmission of the nOPV2 virus with
reversion to a VDPV. The risk is difficult to quantify, but so far, there have been at least 7 separate emergences of
new cVDPV2 linked to nOPV2 (cVPDV2-n) and at least 61 associated paralytic cases worldwide
from these emergences. These are the numbers that have been published in the literature so
far, but the actual numbers are likely higher as nOPV2 use increases globally. However, nOPV2
is estimated to be 80% less likely than Sabin OPV to seed a new cVDPV2. The risk of a new
cVDPV is highest when campaign coverage is low in a population with low immunity against
polioviruses.
When thinking about the balances of risks and harms for the individual recipient, most recipients
will have already been vaccinated with IPV during childhood immunization and are already
protected against paralytic disease. The anticipated benefits of nOPV2 to the individual recipient
would be a higher anti -polio Type 2 antibody titer and increased odds of mucosal immunity to
poliovirus Type 2. For an under -vaccinated person, this would mean additional protection
against paralytic disease. However, for a previously vaccinated person, there is unlikely to be a
clinically significant benefit of vaccination. For potential harms, there is an extremely low but non-zero  risk of VAPP. There also is a risk of chronic infection if nOPV2 is given to a child with
unrecognized immunocompromise.
At the population level, decreased transmission among nOPV2 recipients potentially could result
in the outbreak ending earlier and fewer paralytic cases. Given that the vaccine virus can be
shed in stool and transmitted to others, there likely would be some degree of passive
vaccination of unvaccinated persons, which also would lead to decreased transmission and
fewer paralytic cases. Potential harms at the population level include passive vaccination of the unvaccinated and a risk of VAPP among the unvaccinated, possible ongoing transmission of the nOPV2 virus leading to a new cVDPV2 virus , and possible chronic infection in
immunocompromised persons.
34

  The magnitude of these benefits and harms will depend on nOPV2 coverage and the extent of
mixing between nOPV2 recipients , unvaccinated persons , and immunocompromised persons.
Dr. Kim Thompson and her colleagues at Kid Risk modelled the expected number of paralytic
cases under different mixing scenarios for a cVDPV2 outbreak similar to the 2022 New York outbreak. They compared the number of cases expected with an IPV -only response to
responses that used a Sabin OPV2 or an nOPV2. In their model, they assumed that the number of vaccine doses administered was the same as the number of IPV doses that were actually
administered during the 2022 New York outbreak. They concluded that use of any type of OPV2
likely would have ended transmission slightly earlier than with IPV alone. However, less than 1
additional paralytic case was predicted in all IPV or OPV2 vaccine scenarios. They also ran a similar model for an aVDPV1 outbreak instead of aVDPV2 outbreak. Recall that Type 1
poliovirus infection is associated with a higher rate of paralytic disease than T ype 2. The results
of this model suggested that use of an OPV1 would likely end VDPV1 transmission faster and
result in fewer paralytic cases than use of IPV alone.
When assessing how substantial the desirable anticipated effects of nOPV2 would be on both
the individual and population levels, approximately half of the work group felt the desirable
effects of using nOPV2 in addition to IPV were small. Some members felt that the desirable
effects would be minimal , while some felt they would be moderate. When asked about the
undesirable anticipated effects, the work group was evenly divided between minimal, small, and
moderate. When asked whether the desirable effects of nOPV2 would outweigh the undesirable
effects, half of the work group felt that the desirable effects would not outweigh the undesirable
effects, and that the information favored the use of IPV only. However, about 1/3 of the group
felt that it varies depending on the situation.
Moving to resource use and feasibility , nOPV2 is not yet approved for use in the US. If the US
wanted to use nOPV2, the mechanism for doing so would be the Expanded Access
Investigational New Drug Application (EA-IND), formally known as “Compassionate Use.” This
requires application to the FDA and FDA authorization. If implemented, the nOPV2 EA-IND
program must include signed informed consent by vaccinees and/or their guardians, an enhanced system for monitoring vaccine safety, enhanced surveillance for possible VAPP
cases and environmental surveillance for new VDPVs, and a system for tracking and accounting for every dose for containment purposes. This includes every dose given, every dose wasted,
and doses returned.
The work group had a variety of opinions on whether this would be a reasonable and efficient
use of resources. Half of the work group responded that it was probably not a reasonable use of
resources, but about 1/4 responded that it would vary depending on the specifics of the
situation. The work group also was divided about whether an nOPV2 campaign would be
feasible to implement. Half of the work group responded that it probably would be feasible, but
about a third responded that it probably would not be feasible.
For values and acceptability considerations, tOPV was removed from the US vaccination schedule in 2000 and was replaced with IPV because any risk of VAPP was deemed
unacceptable at that time. This removal might be a barrier to acceptance of a new OPV vaccine
in the future. In addition, the need for a signed informed consent likely will be a deterrent,
especially for those who are concerned about vaccine safety and new vaccines. It is unclear
whether the general public will accept an OPV vaccine if they are already protected from
paralytic infection by IPV. It is unclear whether the general public will accept a vaccine to reduce
community transmission and risk to others if they would not benefit from it individually .
35

     Similarly, it is unclear whether the populations most at risk (e.g., those with low childhood
vaccination coverage and those with high rates of vaccine skepticism ) would accept an OPV
vaccine.
The work group noted that perceptions of risk and vaccine acceptance might shift in an outbreak
setting, particularly if there is more than 1 paralytic case in a community. A clear majority of the
work group agreed that the target population probably does not feel that the desirable effects of
nOPV2 are large relative to the undesirable effects. However, they were divided about whether
there was important uncertainty or variability in how much people would value the main
outcomes. The work group was similarly divided about whether nOPV2 would be acceptable to
key stakeholders. Some felt that it probably would not be acceptable to stakeholders, some felt that it probably would be, and some felt that it would vary.
In terms of equity considerations , there is only 1 manufacturer of nOPV2, BioFarma in
Indonesia, which is managed via a global stockpile. Supply shortages have occurred in the past.
In the US, IPV is readily available and provides protection against paralysis from cVDPV2. In
many countries with cVDPV2 outbreaks, there is limited protection against cVDPV2, unless
there are nOPV2 or Sabin OPV2 campaigns. In terms of equity within the US, the work group
noted that preventing transmission of the outbreak virus does protect unvaccinated, under-
vaccinated, immunocompromised persons. Again, there was a spread of opinions among the
work group members. The plurality of the work group felt that using nOPV2 probably would not
have a significant impact on health equity.
Putting it all together, most of the work group felt that the undesirable consequences of using
nOPV2 during an outbreak in the US probably outweigh or are closely balanced with the
desirable consequences.
In summary, the work group believes at this time that the undesirable consequences of using
nOPV2 probably outweigh or are closely balanced with the desirable consequences. The main
considerations for the work group’ s interpretation was that IPV is readily available in the US and
protects against paralytic disease, and that the primary benefit of adding nOPV2 to an outbreak
response would be to reduce transmission of outbreak virus and reduce risk of paralytic disease in under -vaccinated and immunocompromis ed persons. There were differences of opinion
regarding the value of reducing asymptomatic transmission or ending asymptomatic transmission earlier during an outbreak. The work group was concerned about the extremely
low but non-zero risk of VAPP or new cVDPV2. There was uncertainty about public and
stakeholder acceptance of a nOPV2 vaccine. However, the work group did acknowledge that
the balance of undesirable consequences compared to desirable consequences might shift in
the future depending on size and scope of the outbreak. As modeling showed, the calculus
might be different for a T ype 1 outbreak where more paralytic cases would be expected, and
public perception of risk might be higher.
Dr. Kidd then introduced the topic of fractional doses of IPV . Wild poliovirus Type 2 was
eradicated in 2015, prompting a global switch in April 2016 during which all the Sabin T ype 2
virus was withdrawn from routine immunization. Countries that were still using OPV as part of
routine immunization replaced tOPV with bOPV that contains only Types 1 and 3. At the same
time, it was recommended that countries that still used OPV include at least 1 dose of IPV as
part of their routine immunization schedule. Subsequently, based on clinical trial data and
limited IPV availability in some countries, WHO has supported the use of 2 fractional doses of
IPV (1/5 full dose IPV) given intradermally in place of a single full dose.
36

  Clinical trials have shown that 1 fractional dose of IPV (fIPV) is less immunogenic than 1 full
dose of IPV ; clinical t rial data also have suggested that 2 fractional doses are more
immunogenic than 1 full dose of IPV.
Currently, 6 countries representing about 20% of the global birth cohort use fIPV in their routine
immunization schedules (Bangladesh, Cuba, Ecuador, India, Nepal, Sri Lanka). They all use 2
fractional doses in combination with at least 3 bOPV doses. One example would be India’ s polio
vaccination schedule in which a child would receive 5 doses of bOPV and 2 doses of fIPV. The
current US guidance recommends a total of either 3 or 4 doses of IPV, depending on the age of
the last vaccination. W hen assessing vaccine records for vaccines administered outside the US,
the guidance is that only tOPV doses or IPV doses are considered valid for the US vaccination
schedule. If a child who was vaccinated under the India vaccination schedule immigrated to the
US and wanted to attend school in the US, current guidance is that none of their bOPV or fIPV
doses would be considered full doses. The child would need either 3 or 4 full IPV doses to be
considered fully vaccinated against polio in the US.
Therefore, the question for the work group was, “S hould 2 fIPV doses administered outside the
US be counted as either 1 or 2 doses toward the US vaccination schedule?” A meta-analysis
was conducted to update to the meta-analysis that was previously published in 2021. Overall, 2 fractional doses were associated with higher rates of seroconversion compared to 1
full dose of IPV. Infants receiving 2 doses of fIPV were 1.5 times as likely to seroconvert
compared to infants who received 1 full dose of IPV. Moving to comparisons between 2
fractional doses and 2 full doses , 2 fractional doses were associated with slightly lower rates of
seroconversion than 2 full doses of IPV. This especially is the case when administered at
younger ages. Peak antibody titers are also lower after 2 fractional doses compared to 2 full
doses. Based on this information, the work group group agreed with the following proposed
language to be included in CDC Clinical C onsiderations for persons receiving polio vaccines
outside of the US :
For persons who received fractional (1/5 full dose) IPV administered intradermally
outside of the United States, 2 fractional doses of IPV (fIPV) should be considered valid and counted as 1 full intramuscular dose of IPV toward the US vaccination schedule.
If a person received only 1 dose of fIPV, this dose should not be considered valid or counted toward the US vaccination schedule.
Following discussion, several ACIP members expressed that they thought it was reasonable to accept 2 fractionated doses as 1 IPV dose and agreed with the work group’s recommendation.
PUBLIC COMMENTS
The floor was opened for public comment on February 28, 2024, at 1:40 PM E ST. The
comments made during the meeting are summarized in this document. Members of the public
also were invited to submit written public comments to ACIP through the Federal eRulemaking
Portal under Docket Number ID CDC-2024-0001. Visit regulations.gov for access to read
comments received.
37

   Diana Olson
National Foundation for Infectious Diseases
Diana Olson from the National Foundation for Infectious Diseases thanked the committee for its
work .  She highlighted the public health and economic benefits of COVID -19 vaccines but
pointed out that coverage with an updated 2023-2024 COVID -19 vaccine remains low .
Immunization rates for other recommended vaccines also remained below public health goals. Only about half of US children and adults have received an influenza vaccine during the current
season and only about 22% of eligible adults aged 60 years and older and about 16% of eligible
pregnant women have received an RSV vaccine. Clearly, there is more work to be done to build vaccine confidence, address health disparities, and increase overall immunization rates. NFID
supports implementation of a Vaccines For Adults program to build upon the Vaccines for
Children and Bridge Access Program and further expand access to these lifesaving tools;
continued support for US vaccine safety systems; and strong public health infrastructure to help
ensure that ACIP, CDC, and state and local public health agencies have the resources to do
their important work.
Mr. Robert Blancato
Executive Director
National Association of Nutrition and Aging Services Programs
Mr. Blancato spoke as Executive Director of the National Association of Nutrition and Aging
Service Programs (NANASP) and on behalf of 18 other national aging and patient advocacy
associations , calling on ACIP to reverse your June 20 recommendation requiring shared
decision-making for the use of the new RSV vaccines for adults 60 and over. CDC has reported
that only 21.9% of adults and reported receiving the RSV vaccine; Mr. Blancato stated that this
low coverage was a consequence of ACIP’s recommendation with shared clinical decision-
making, which he stated was difficult for health care providers to implement.  He stated that
these organizations also oppose shared decision-making due to its negative impact on
vulnerable adults who are part of already underserved communities. He stated support for co -
administration of these vaccines and that he was encouraged by the morning’s discussion on
the recommendation for an additional COVID vaccine shot and the resulting amendment in favor of “should” instead of “may. ” If the goal is preventing serious health outcomes in older
Americans from respiratory illness, clear, broad, and easy to communicate guidance should be the standard for adult vaccines.
Martha Nolan, JD Senior Policy AdvisorHealthyWomen
Martha Nolan, Senior Policy Advisor for HealthyWomen, asked for clarification of
recommendations in several areas.  She expressed concern around how the seasonal
recommendations for maternal RSV vaccine translate to reimbursement and coverage. Specifically, many are confused about whether there is cost-sharing on the part of the patient if they receive the vaccine after January 31, 2024, b ecause the CDC guidance notes that in
certain US jurisdictions where RSV seasonality differs, providers may consider RSV vaccination
after January 31, but it is not clear if insurance will cover the cost. She asked that ACIP consider
ways to ensure there are no coverage barriers for patients, particularly when considering future seasonal recommendations. Lack of coverage for a vaccine is a barrier that often leaves patients to forego that care option. She expressed discouragement over the low uptake of RSV and COVID vaccines in older adults during the ‘ 23-‘24 respiratory season.
38

  Despite there being many tools to protect ourselves against respiratory illnesses than ever
before, there is also increasing confusion about who should receive what vaccine and when.
She asked ACIP to evaluate existing guidance and provide necessary changes to ensure clarity
around who should receive them and when and ensure coverage for all populations.
Hannah Berk
Unaffiliated Community Member
Hannah Burke asked the committee to support the proposed recommendation on a booster
dose of the COVID -19 vaccine in this meeting and to develop action steps to go further after this
meeting. She stated that people of all ages and health statuses need updated COVID vaccines
covered by insurance and/or public funds at least every 6 months. Twice annual vaccination
allows healthy people to safely share space with high-risk family and friends so long as they
take precautions, which include vaccinating after immunity wanes significantly after 4 to 6
months and multiple COVID -19 infections compound systemic damage to the body that makes
any person more vulnerable to illness and disability, even if they are otherwise healthy. She
expressed her hope that the committee will approve the proposal to announce COVID vaccine
recommendations on an earlier timeline this year, which can help ensure appropriate time to
increase the accessibility of these vaccin es. Ms. Burke shared that many of her friends and
relatives have asked their doctors about booster availability and have been told they don't need
the vaccine, and uninsured friends received their boosters months later than they could have because they hadn't heard about the Bridge Program .  She expressed her support for a “should”
recommendation on boosters for older adults and for an expedited vaccine decision-making
timeline. She urged the committee to make updated vaccines accessible twice annually for
people of all ages and at no cost and to recommend continued vaccination in the clearest, strongest terms.
Maria Shreve, RN
Parents, Nurses, Herself
Ms. Shreve is a Registered Nurse and said that her family is so grateful to have access to
children's COVID vaccines and now the new RSV vaccine, but it wasn't easy. She asked the
committee to make children's vaccines available before school starts this year, which would help
decrease transmission and infection.  She said that children's uptake would be higher if supply was available and urged support for more accessible locations for kids of all ages , and mass
vaccination clinics where parents can take kids of all ages for vaccines together instead of
taking one to a pharmacy, one to the pediatrician, and one to the Minute Clinic.  She said a
better plan is quickly needed for the development and implementation of more RSV and COVID treatments . Unvaccinated children's hospitalization rates last year with COVID were as high as
the elderly, which could have been prevented by increased access to vaccines . She also
expressed support for options that allow access to vaccines every 6 months instead of yearly.
39

  AGENCY UPDATES
Centers for Disease Control and Prevention
Dr. Demetre Daskalakis highlighted CDC’s work during the winter respiratory season. Influenza,
COVID -19, and RSV are still elevated in some parts of the country . As of February 10th, 22% of
adults ≥18 years of age and 12% of children 6 months to 17 years of age have received COVID-
19 vaccination. Pharmacies have administered over 750,000 doses of COVID -19 vaccines and
over half a million doses were ordered by public health providers through the Bridge Access
Program. In the US, influenza vaccine coverage rates have decreased; about 6.5 million doses
of influenza vaccine have not been given this season compared to last.
The ACIP was a very important part of RSV vaccine launches for pregnant people and
immunization launches for newborns. Despite an initial supply and demand mismatch with
nirsevimab, 30% of infants <8 months of age received nirsevimab and about 16% of eligible
pregnant persons received an RSV vaccine between 32 and 36 weeks gestation. In the context
of new vaccine products, this is remarkable uptake.
As of February 22 , 2024, a total of 35 cases of measles have been reported this year in 15
jurisdictions compar ed to 58 cases of measles last year in 20 jurisdictions in the US. This is not
a good slope of the curve, particularly given that measles is preventable with safe and effective
vaccines. As measles continues to increase in other parts of the world, importations continue to
happen. When importations occur in places where coverage is low, there is risk for ongoing
larger outbreaks.
Centers for Medicare and Medicaid Services
Mary Beth Hance began by announcing the passing earlier in the month of Dr. Jeffrey Kelman
following an illness. Dr. Kelman was a Centers for Medicare and Medicaid Services (CMS )
colleague who was the C hief Medical Officer for CMS ’s Center for Medicare. He was involved
with the ACIP for many years, representing CMS on many work groups . Dr. Kelman was a
pulmonologist by training, which fit perfectly into much of the work he did supporting CMS on
the influenza, pneumococcal, COVID, and many other ACIP work groups. He also worked
closely with FDA on using data and was absolutely committed to the idea that valuable data
within agencies could be used across agencies . Dr. Wharton and other colleagues in
attendance mourned the loss of Dr. Kelman and acknowledged his many important
contributions .
In terms of updates, on February 12, 2024, CMS issued an updated Medicaid and CHIP vaccine
toolkit that reflects the change in commercialization of COVID vaccines and the Inflation
Reduction Act provisions that impacted mandatory coverage of vaccines for adults in Medicaid.
Food and Drug Administration
Dr. David Kaslow reported that since the last FDA agency report during the October 2023 ACIP
meeting and apropos of discussions earlier in the day on chikungunya, FDA approved IXCHIQ®,
a vaccine indicated for the prevention of disease caused by chikungunya virus in individuals ≥18
years of age who are at increased risk of exposure to chikungunya virus ( CHIKV ). This
indication was approved under accelerated approval based on anti -CHIKV neutralizing antibody
titers.
40

  Continued approval for this indication may be contingent upon verification and description of
clinical benefit in confirmatory studies. The highlights of the US prescribing information include
warnings and precautions that IXCHIQ® may cause severe or prolonged chikungunya- like
adverse reactions. Other regulatory actions include scores of supplemental Biological License
Applications (sBLAs), some pertaining to manufacturing changes and some regarding labeling
changes.
Given the ACIP agenda for the next day , Dr. Kaslow highlighted the work FDA continues to do
to monitor the safety and effectiveness of vaccines for respiratory illnesses using the Biologics
Effectiveness and Safety System (BEST) and the CMS System. Ongoing projects include safety
and effectiveness of RSV vaccines, influenza vaccines, and COVID -19 2023-2024 formula
vaccines. Although the Vaccines and Related Biological Product Advisory Committee
(VRBPAC) has not met since the October 2023 ACIP meeting, FDA anticipates convening
VRBPAC twice before the June 2024 ACIP meeting. The VRBPAC is scheduled to meet on
March 5, 2024, in open session to discuss and make recommendations on the selection of
strains to be included in the influenza vaccine for the 2024-2025 influenza season. As
mentioned earlier in the day, VRBPAC is scheduled to meet in open session on May 1 6, 2024,
to discuss and make recommendations on the selection of strains to be included in the 2024-
2025 formula for COVID -19 vaccines. Other convenings of VRBPAC may occur as needed. As
in the past, Dr. Kaslow took the opportunity to personally thank the review teams, their
supervisors, and management at Center for Biologics Evaluation and Research (CBER) who
worked and continue diligently to conduct research and review to protect and enhance public
health. In addition, he thanked CDC staff for their many contributions and their collegial support
of collective efforts to protect and enhance public health for immunization.
Health Resources and Services Administration
CDR Reed Grimes, MD, MPH provided the Health Resources and Services Administration
(HRSA) update the National Vaccine Injury Compensation Program (VICP ) continues to actively
process claims . In Fiscal Year 2024, as of January 1, petitioners have filed 314 VICP claims.
Over $41 million was awarded to petitioners and over $13 million was awarded to pay attorney ’s
fees and costs. In addition, the VICP had approximately 600 claims alleging vaccine injury
awaiting activation for review. Previously, there was nearly a 12-month wait period between
when a petition was found to have adequate medical records to review by a HRSA provider and
when a review was completed. As of January 1, 2024, the wait period has been reduced to less
than 1 month. More data about the VICP can be found on its website at www.hrsa.gov/vaccine-
compensation/data/index.html .
In the decade prior to COVID -19, fewer than 500 claims had been filed with the
Countermeasures Injury Compensation Program (CICP ). CICP received a direct appropriation
for the first time in Fiscal Year 2022, and the program has used those funds to increase its
capacity to conduct medical reviews by hiring and training new review staff and contractors as well as to pay compensable claims and improve IT and other communications with requesters. As of January 1, 2024, 12,854 claims alleging injuries or death from COVID -19
countermeasures had been filed with the CICP, including 9,682 claims alleging injuries or death
from COVID -19 vaccine. CICP has rendered decisions on 2,214 COVID -19 claims as of
January 1, 2024, representing more than 4 times in the prior decade. More information about
the CICP can be found at its website at www.hrsa.gov/cicp .
41

  Indian Health Services
Matthew Clark, MD, FAAP, FACP reported that the Indian Health Service (HIS) continues to
prioritize vaccination as its principal clinical and public health prevention priority. As part of the
IHS National E3 Vaccine Strategy, the IHS seeks to ensure that every patient at every
encounter is offered every recommended vaccine when appropriate. Following announcement of this IHS strategic initiative in November 2022, the IHS established the E3 Vaccine Champions Pilot Program in March 2023. Since then, the IHS has designated 28 vaccine
champions pilot sites in 9 of the 12 IHS areas, including federal, tribal, and urban programs. IHS
has shared clinical and community resources and multidisciplinary best practices to cross -
pollinate the IHS system of care and to improve vaccine coverage rates in tribal communities.
As part of a proactive strategy of outreach, education, and engagement with its partners in tribal
communities, the IHS 2023-2024 Respiratory Viral Vaccine Campaign has worked to ensure timely access to immunizations for COVID, seasonal influenza, and RSV among its vulnerable
service population across the age spectrum.
Following reported supply chain constraints in the fall, IHS worked diligently to secure a
supplemental supply of the long-acting monoclonal antibody, nirsevimab, to ensure that this life-
saving immunization was available in support of ACIP recommendations for administration of
nirsevimab to AI/AN infants and children up to 19 months of age. To date, nearly 8,000 supplemental doses of nirsevimab have been distributed and administered to mitigate the risk of serious RSV disease among infants and children in Indian Country. Due to persistently elevated rates of respiratory viral illness in Indian Country, in collaboration with IHS obstetric and
pediatric subject matter experts (SMEs), last month the IHS Chief Medical Officer, Dr. Loretta
Christensen announced extension of the period for administration of maternal RSV vaccine to
eligible pregnant AI/AN persons through the end of February for this season in seeking to
mitigate the risks of RSV in IHS’s high-risk service population. Preliminary surveillance suggests favorable uptake of novel RSV countermeasures in Indian Country. This is especially true in regions historically most impacted by high rates of RSV -related morbidity and mortality, such as
the YK Delta Region in Alaska, where proactive efforts by tribal partners included bush plane flights to over 25 vil lages to administer nirsevimab to eligible infants and children, many of
whom also received other ACIP recommended vaccines. Moving forward in collaboration with its partners in tribal communities, IHS will continue to promote access, quality, value, and equity related to immunizations in Indian Country.
National Institutes of Health
Dr. John Beigel provided several updates from the National Institute of Health (NIH) on vaccine-
related research of interest to the ACIP. Regarding NIH leadership, In November 2023, Dr.
Monica Bertagnolli started as the 17
th Director of the NIH. She is the first surgeon and second
woman to hold the position. Nominated by President Biden, she was confirmed on a bipartisan
basis in the US Senate and transitioned from her role as Director of the National Cancer
Institute (NCI) , a position she held since October 2022.
For COVID -19, Dr. Beigel highlighted 2 studies about the value of maternal vaccine. First was a
study that demonstrated maternal vaccination may prevent infant COVID -19 in a cohort. Study
researchers aimed to quantify protection against infection from maternally -derived vaccine
antibodies in the first 6 months of an infant’ s life. Higher transplacental binding and neutralizing
antibodies substantially reduced the COVID -19 infection in the infants. Until infants are age-
eligible for vaccination, maternal vaccination provides passive protection against symptomatic
infection during early infancy.
42

  These same findings extend to preterm infants. In a separate study, it was shown that preterm
infants born to people who are vaccinated for COVID-19 have roughly the same antibody titers
as those of term infants. Moreover, in all infants, antibodies to the spike protein were higher
among those born to individuals who received 3 or more vaccines before delivery compared to
those who only had 2 . These findings may help allay concerns that fewer antibodies might pass
from preterm infants compared to term infants.
In a study regarding the ancillary benefits of COVID -19 vaccines versus a prospective cohort
study of adults , researchers identified SARS- CoV-2 infections and followed them for the
presence of post-acute sequelae. COVID vaccination not only prevented disease, but also was
associated with lower prevalence and severity of long COVID symptoms. There also was an
interesting study about looking at the spike in preterm birth rates that started at the beginning of
the pandemic. That analysis showed that by late 2022, widespread COVID-19 vaccination in
pregnant people likely halted the spike in preterm infants, and those rates have come down
toward normal. This underscores the need for pregnant people to keep current on COVID -19
vaccination.
In October 2023, the Nobel Prize for Physiology or Medicine was awarded to Drew Weissman,
MD, PhD and Katalin Karikó, PhD for their work on messenger ribonucleic acid (mRNA) that
enabled the development of mRNA vaccines . Dr. Weissman and Dr. Karikó had decades long
work on mRNA with incremental steps in the science. Ultimately, those steps and those
scientific advancements were critical to enable the unprecedented development of the mRNA
vaccines that stemmed the pandemic.
For influenza, Dr. Beigel highlighted a study that evaluated 2 doses of high-dose trivalent
influenza vaccine (HD-TIV) compared to standard dose quadrivalent influenza vaccine in a
pediatric hematopoietic stem cell transplantation (HSCT) population. The high-dose vaccine
resulted in higher antibody responses, especially for influenza A. Because influenza causes
substantial morbidity and mortality in that population, optimization of vaccine strategies is
critical. The use of high- dose inactivated vaccines may be a practical strategy to overcome the
poor immunogenicity in that population.
Office of Infectious Disease and HIV/AIDS Policy
CDR Valerie Marshall reported that the Interagency Vaccine Working Group (IVWG) of the HHS
is scheduled to convene in March 2024 to deliberate on an interagency progress report which
addresses the achievements and strides made from 2021 to 2023 toward achieving the goals
outlined in the Vaccines National Strategic Plan (VNST). This collaborative effort underscores
the commitment of multiple federal agencies toward transparent communication and the pursuit of vaccination goals. The National Vaccine Advisory Committee (NVAC) held a meeting on
February 22 -23, 2024, to discuss critical policy matters related to vaccination. The committee’ s
deliberations included a discussion on the resurgence of measles cases, which underscored the pressing need for proactive public health measures to improve vaccine confidence and counter
misinformation about vaccines.
With no additional business posed for the day , the ACIP meeting stood in recess until 8:00 AM
on February 29 , 2024.
43

 THURSDAY:  FEBRUARY 2 9, 2024
WELCOME AND INTRODUCTIONS
Call to Order/Roll Call
Dr. Melinda Wharton (ACIP Executive Secretary & Acting Chair, CDC) called to order and
presided over the February 28-29, 2024 ACIP meeting because the process for the new ACIP
Chair to join the committee had not yet been completed. As allowed under the ACIP charter, the ACIP’s six Ex Officio members were temporarily designated as voting members. She then
conducted a roll call, which established that a quorum was present. A list of Members, Ex
Officios , and Liaison Representatives is included in the appendixes at the end of this summary
document. No COIs were identified for the second day of this meeting.
RESPIRATORY SYNCYTIAL VIRUS (RSV) VACCINES ADULTS
Dr. Camille Kotton, Chair, ACIP Adult RSV Work Group, introduced the RSV session, reminding
everyone that in June 2023 ACIP recommended that adults ≥60 years of age may receive RSV
vaccination using shared clinical decision -making. There are currently 2 licensed and
recommended products for adults ≥60 years of age:
GSK RSV vaccine (AREXVY), which is a 1-dose adjuvanted (AS01E) recombinant prefusion
F (preF) protein vaccine.
Pfizer RSV vaccine ( ABRYSVO
®), which is a 1-dose recombinant preF vaccine.
In October, GSK presented data to the ACIP demonstrating that the humoral immune response to a single dose of GSK RSV vaccine in adults 50─ 59 years of age was non-inferior to that in
adults >60 years of age. The ACIP Adult RSV Work Group shared their early interpretations of
this data and the potential role of RSV vaccination in adults younger than 60 years of age,
including subpopulations who would benefit most from vaccine and equity implications. At that
time, ACIP members expressed the importance of reviewing safety surveillance data to inform future preferred policy recommendations.
The work group has been simultaneously reviewing additional data to prepare for the upcoming
policy decisions, especially focusing on the risk of severe RSV disease in adults 50 ─59 years of
age, especially those with chronic medical conditions ; RSV vaccine uptake among different
demographic groups ; and potential policy options that would transition away from shared clinical
decision-making. The work group also has begun reviewing data from Moderna on their
investigational RSV vaccine (mRNA -1345) in adults ≥60 years of age.
Dr. Rituparna Das (Moderna) presented clinical data on Moderna’ s investigational RSV
candidate vaccine, mRNA -1345, among adults ≥60 years of age. The data package on adults
≥60 years of age was submitted to the FDA for review in September 2023. The i nvestigational
RSV v accine, mRNA -1345, is a lipid encapsulated mRNA -based vaccine that encodes the RSV
fusion (F) glycoprotein stabilized in the prefusion confo rmation. The prefusion F protein contains
epitopes that elicit antibodies that are potently neutralizing and cross-reactive between RSV-A
and RSV -B. Following administration of a single 50 microgram (μg) dose, robust
immunogenicity was observed in Phase 1 that was persistent through 12 months post-
vaccination.
44

  The pivotal Phase 2/ 3 safety and efficacy trial, Study 301, enrolled adults ≥60 years of age.
Participants were randomized 1:1 to receive mRNA -1345 or saline placebo and 24 months of
planned follow-up. Randomization was stratified by age (60─74 years and ≥75 years) and
presence or absence of congestive heart failure (CHF) or COPD . The study started in
November 2021 and weekly surveillance was conducted via electronic diary to look for RSV
symptoms. Given the importance of risk factors on morbidity and mortality with RSV in older
adults, participants also were included with a number of high-risk medical conditions. Frailty
status was assessed of all participants at entry using the Edmonton Frail Scale (EFS).
Participants were characterized on a 0- to 17-point scale as being fit (0-3) , vulnerable (4-5), or
frail (6-17).
A total of 36 ,550 participants were enrolled as of the April 30, 2023 data cutoff, a pproximately
50% of whom came from the US. V accinations in Study 301 began in late November 2021 and
continued through December 2022. The primary analysis was driven by the accumulation of a
target number of cases, and study success was declared at that time. The study continued in a blinded fashion. When nearly all study participants reached 6 months of follow -up, an additional
analysis was conducted as agreed with the FDA. The median follow -up for this additional
analysis was almost 9 months, with a range up to 17.7 months.
The demographics of Study 301 were well -matched between the vaccine and placebo
recipients. The median age was 67 years , 30% of the study participants were 70─ 79 years of
age, just under 3,000 participants were ≥80 years of age, 12% were Black or African American,
and 33% identified as Hispanic or Latino. R ace/ethnicity in the study was representative of the
US population. Approximately 2,600 participants had CHF or COPD , almost 1/3 of trial
participants had 1 or more of the comorbidities that put them at higher risk for RSV -related
morbidity or mortality , 16% percent of the population was considered vulnerable, and 6% were
considered to be frail.
The median safety follow -up was 8.6 months and almost all participants had been followed for
more than 6 months. In general, mRNA-1345 was well -tolerated. Injection site pain was the
most common local reaction, followed by axillary swelling or tenderness. Most events were mild,
with onset within 1 to 2 days post-injection and lasting 1 to 2 days. Solicited systemic reactions
of fatigue, myalgia, and headache were the most common. Fever was rare and most reactions
were mild, with onset within 1 to 2 days post-injection and lasting 1 to 2 days. Severe events
also were rare. Unsolicited events were well -balanced overall between vaccine and placebo
recipients . The occurrence of SAEs, AEs leading to discontinuation, and AESIs also were
balanced between vaccine and placebo recipients. There was 1 event in the vaccine group,
which was aspiration following intoxication. There were 6 fatal events in the placebo group.
There were no cases of Guillain -Barré syndrome ( GBS) or acute disseminated
encephalomyelitis ( ADEM). There was no imbalance in neurological disorders such as Bell ’s
palsy or facial paralysis. For cardiac events, there was no imbalance in cardiac arrhythmias,
including atrial fibrillation. No myocarditis was identified in vaccine recipients and there were no
cases of pericarditis with onset within 6 weeks of vaccination.
Co-primary endpoints were protection against RSV -lower respiratory tract disease (RSV -LRTD)
with ≥2 or ≥3 signs and symptoms. Protection against RSV -associated acute respiratory
disease (ARD) and RSV -related hospitalizations were key secondary endpoints. RSV-LRTD
was defined as new or worsening of ≥2 or ≥3 of signs/s ymptoms for ≥24 hours and RSV -ARD
was defined as new or worsening of ≥1 s igns/s ymptoms for ≥24 hours. Identification of a
symptom prompted a visit to the site and a nasopharyngeal swab.
45

  All cases had to be confirmed for RSV by reverse transcription polymerase chain reaction (RT -
PCR). C ontinuous year -round weekly surveillance was conducted throughout the study.
The target number of cases for the first analysis was met in November 2022 which became the
primary analysis. Follow -up was a median of 3.7 months , with a range from 0.5 to 12.6 months.
The efficacy against RSV -LRTD with ≥2 symptoms was 83.7% (66.0%, 92.2%) and efficacy
against RSV-LRTD with ≥3 symptoms was 82.4% (34.8%, 95.3%). Efficacy against RSV-ARD,
the secondary objective, was 68.4% (50.9%, 79.7%). The observed RSV cases were subtyped
for RSV-A and RSV-B, with efficacy observed for both RSV -A and RSV -B.
Efficacy was maintained in older ages and was similar for those with or without co-morbidities and in those who were considered vulnerable or frail. There were no hospitalizations in the
primary analysis. For LRTD with shortness of breath as a marker of severity, efficacy was
86.7%. For RSV cases that were medically attended in the emergency department or urgent
care, there were 5 cases in placebo recipients and no cases among vaccine recipients.
An additional analysis of efficac y was conducted at the end of April 2023; the median follow-up
was 8.6 months , with the upper bound of the range being 17.7 months. The efficacy of mRNA -
1345 against RSV -associated LRTD and ARD remained high, with overlapping confidence
intervals to the primary analysis estimates over this longer follow-up time. V E against LRTD with
≥2 symptoms and ≥3 symptoms was 63% (48.7%, 73.7%) and for ARD was 54% (40.5%,
64.3%). Protection was seen for both RSV-A and RSV-B.
Efficacy was consistent for adults 60 ─69 years of age and 70 ─79 years of age. Among adults
≥80 and older, there were only 11 cases of LRTD with ≥2 symptoms , precluding the
conclusions. The group of adults ≥ 80 years of age had the lowest incidence of RSV in the
placebo recipients compared to adults 60─69 years of age and 70─ 79 years of age, perhaps as
a carryover of pandemic measures in these trial participants. Efficacy in participants with co-
morbidities and participants who were vulnerable or frail also were very consistent in this
analysis. Assessing the impact of mRNA -1345 on preventing severe RSV as indicated by the
shortness of breath measure, efficacy was 74.6% (50.7%, 86.9%). More participants in the
placebo groups sought a higher level of care in an ED or UC , with efficacy of 61.8% (-7.35,
86.45) . A total of 2 participants were hospitalized, a 73-year -old and an 84 -year-old, both of
whom had asthma and were from the placebo group. There were no hospitalizations in the
vaccine group.
The vaccine was immunogenic , result ing in an 8- fold rise in the RSV -A neutralizing titers and a
5-fold rise in the RSV -B neutralizing titers. Responses were consistent across the age spectrum
and there was no evidence of decreasing response as age increased . Cellular immune
responses were evaluated for CD4 and CD8 in a separate study of adults 50─ 75 years of age.
The vaccine was found to elicit strong and persistent T-cell responses as well. In the Phase 1
study, antibody remained detectable at 12 months, w ith GMTs 2-to 3-fold over baseline for both
RSV-A and RSV-B. In that study, re- vaccination at 12 months was evaluated. Administration of
a second dose of mRNA -1345 increased both RSV -A and RSV-B neutralizing titers 5-to 7-fold.
The question of re-vaccination is important since protection from RSV by natural infection is not
lifelong, but additional durability data will be needed to determine the timing. Moderna is
studying re- vaccination at 1 and 2 years in Phase 3 studies.
46

 Co-administration was explored with standard-dose quadrivalent influenza vac Ccine (Afluria)
and the Moderna bivalent COVID -19 vaccine in adults ≥50. Concomitant administration of the
RSV and influenza vaccines was immunogenic for RSV -A, RSV-B, and all 4 influenza types and
was well -tolerated in terms of local and systemic reactions. The same trend was observed with
concomitant administration of mRNA -1345 and COVID -19 vaccine.
To summarize, the mRNA -1345 vaccine was well-tolerated in over 19,000 adults ≥60 years of
age. No cases of GB S, ADEM , or other safety concerns were identified. The vaccine was shown
to be efficacious , met all pre-specified criteria for licensure, and continued to be efficacious
through a median of 8.6 months with a range up to 17.7 months. The vaccine prevented severe
RSV disease as evaluated by the prevention of shortness of breath and medically -attended
AEs. Strong antibody and cellular immune responses were seen through 12 months, and
boosting was evident at 1 year. The antibody responses were similar across age groups,
including those ≥ 80 years of age. Pre-specified immunogenic criteria were met, and no new
safety signals were seen with concomitant administration.
Dr. Daley observed that VE was lower in the later data than the earlier data and asked Dr. Das
to expand on how the results were interpreted for the durability of a single dose.
Dr. Das indicated that durability of a single dose was assessed in several ways . The confidence
intervals at both time points overlap ped. A detailed time-to-event (TTE) analysis was performed,
which was reassuring in that the cases that were occurring in the longer follow -up were not in
people who were vaccinated earlier. Efficacy also was consistent in a before 6 months and after
6 months analysis. Perhaps there is some waning, but there also is an effect from underlying
force of infection.  Immune responses lasting out to 12 months are also reassuring. Dr. Long said that regarding the immunogenicity of the second dose at 1 year, “boost” is a word
that could be used. “Reinforcing might be another word. However, no data were shown to
suggest that there was an anamnestic response. Since the GMTs after the second dose did not
quite equal the titers after an initial dose in the mRNA vaccines against COVID and influenza,
she wondered whether a similar lack of robustness was observed after a second dose or if this
specific to RSV and if there were any ideas about why this is different. Dr. Das responded that for RSV, there is still a highly seropositive population. While a good
response was observed in these small studies, both 1 and 2 years are being examined to
determine whether there is any benefit to a 2-year gap. In terms of COVID -19 vaccines, the
boosts have gone higher than the initial vaccination, but the immunologic experience with
COVID at the point that those studies were conducted was quite different and it may not be
completely fair to put those vaccines side-by -side. To reiterate, persistent immune responses
are observed through 12 months. While boosting is observed with a second dose, it does not
recapitulate the original dose, but it is quite close. Again, Moderna will be bringing the larger
studies forward for both 1-year and 2-year revaccination later in 2024.
Dr. Beigel (NIH) asked whether Moderna had thought about or started work on correlates of
protection to help understand what titers are actually needed.
Dr. Das responded that Moderna is very well -positioned to perform a correlates of protection
analysis since samples were collected from every person in this study at baseline and Day 29.
Initial analyses have been performed of the correlates, which show that RSV neutralizing titers
are very well -correlated with protection. These data are being investigated in more detail to look
for whether a threshold can be determined.
47

  Rebecca C. Woodruff, PhD, MPH (CDC/NCCDPHP) presented preliminary results exploring
chronic conditions as risk factors for RSV -associated hospitalizations. Using methods
developed for a previous study, 3 data sources were leveraged to calculate RSV hospitalization
rates during the 2017-2018 RSV season stratified by chronic condition and age group. The data
source for the numerator was RSV -NET and the data sources for the denominator were the
BRFSS and Census county -level population estimates.
RSV-NET is a population-based hospitalization surveillance platform. Currently, RSV -NET
conducts active population-based surveillance of laboratory -confirmed RSV-associated
hospitalizations for more than 300 acute care hospitals in 58 counties across 12 states (Oregon,
California, Utah, Colorado, New Mexico, Minnesota, Michigan, New York, Connecticut,
Maryland, Tennessee, Georgia) . This area includes about 8.6% of the US population. In the
2017-2018 surveillance season, the catchment area was slightly small er. It included about 38
counties across 8 states. Hospitalizations reported to RSV -NET include all of those where a
positive RSV test was reported within 14 days prior to or during hospitalization. Testing for RSV
is driven by clinical judgment and facility policies.
The BRFSS is an annual CDC -funded telephone- based health survey that operates in 50 US
states, DC, and 3 US territories. BRFSS uses both landlines and cell phone numbers for
sampling and collects about 400,000 interviews of adults each year. The questionnaire
assesses a variety of health-related characteristics, including self-reported history of select
chronic conditions. The BRFSS sample is designed to represent the civilian community -dwelling
adult population ≥18 years of age in each jurisdiction. Adults who are not community -dwelling,
including those living in nursing homes or other LTCFs , are not eligible to participate.
The study evaluated 9 chronic medical conditions as potential risk factors for RSV-associated
hospitalization, including a sthma; chronic kidney disease (CKD); c hronic obstructive pulmonary
disease (COPD), coronary artery disease (CAD) , current smoking, diabetes mellitus , obesity
(body mass index 30-39 kg/m2), severe obesity (body mass index ≥40 kg/m2), and s troke. This
list was determined based on chronic conditions that were abstracted by RSV -NET and included
in the BRFSS questionnaire.
RSV hospitalization rates were calculated using RSV-NET data to obtain counts of RSV
hospitalizations among community -dwelling adults ≥50 years of age with and without chronic
medical conditions of interest. These counts served as the numerator data in the rate
calculation. To align with the BRFSS data, RSV -NET cases were excluded among adults living
in nursing homes or other LTCFs . Next, a combination of BRFSS and the C ensus data were
used to obtain estimated counts of community -dwelling adults ≥50 years of age with and without
chronic medical conditions for the 38 -county RSV -NET catchment area, which served as the
denominator data for the rates. These data were used to calculate RSV hospitalization rates per
100,000 population among adults with and without each chronic medical condition, which was
summarized by 3 age groups : 50─ 64 years of age, 65─ 74 years of age, and ≥75 years of age.
Finally, rates were multiplied by burden multipliers to account for the under-detection of RSV
among hospitalized adults and sensitivity of diagnostic tests. To calculate the rate ratios, the
RSV-associated hospitalization rates in adults were divided with versus without chronic medical
condition overall and within each age group. Monte Carlo simulation and generalized Poisson
models were used to estimate rate ratios and 95% Monte Carlo intervals after adjusting for sex
and race or ethnicity group.
48

  For adults 50─64 years of age, the RSV hospitalization rate was about 7.9 times higher for
adults with versus without CKD, 5.8 times higher for adults with COPD, about 4 times higher for
adults with severe obesity or CAD, and about 2 to 3 times higher for adults with asthma,
diabetes , and current smokers. The RSV hospitalization rates were similar for adults regardless
of obesity or history of stroke. To put these rates into the context, adults ≥75 years of age have
substantially higher hospitalization rates compared with adults 50─ 60 years of age.
For adults 65─74 years of age, the rates were higher across the board than for adults 50─ 64
years. There also was a generally similar pattern with RSV hospitalization rates at about 6 times
higher for adults with CKD, 4.5 times higher for adults with severe obesity, 4.2 times higher for
adults with COPD, and 2 to 3 times higher for adults with asthma, current smokers , CAD, or
diabetes. For context, the RSV hospitalization rate was about 6.1 times higher for adults ≥75
years of age with versus without CKD , 4.2 times higher for adults with COPD, and about 2 to 3
times higher for adults with severe obesity, asthma, or CAD.
RSV hospitalization rates were lowest among adults in the youngest age group of 50 ─64 years
of age and were highest among adults in the oldest age group of ≥ 75 years of age. Although the
absolute rates clearly increased with age group, the adjusted rate ratios did not. Among adults
≥50 years of age, RSV hospitalization rates were about 6.5 times higher for adults with CKD,
about 4.6 times higher for adults with COPD, around 3 times higher for adults with asthma or
severe obesity, and about 2 times higher for adults with CAD, diabetes, and current smokers.
The adjusted rate ratio for stroke and obesity were not statistically significant.
Adults with 2 or more chronic conditions had the highest RSV hospitalization rates compared to
those with no chronic conditions. The adjusted rate ratios comparing the RSV hospitalization
rate among those with 2 or more conditions to those with no conditions ranged from about 6.4 to
12.4 depending on the age group. The adjusted rate ratios comparing RSV hospitalization rate
among those with 1 condition to those with no conditions ranged from about 2.6 to 2.9
depending on the age group.
Based on these preliminary results, the conclusion was that select chronic medical conditions
were associated with greater rates of RSV -associated hospitalization among community -
dwelling adults ≥50 years of age and varied by condition and age group. This information could
help identify populations that might benefit most from RSV vaccines available to adults.
Dr. Carla Black (CDC/NCIRD) presented data on implementation of older adult RSV vaccines
during the 2023-2024 season.  Based on information from immunization information systems
(IISs) submitted by jurisdictions to CDC through December 2023, coverage among adults ≥60
years of age who had received ≥1 d ose RSV v accine varied by state and ranged from about 5%
to about 18% among the 37 states reporting at that time. D ata are not available from all states,
so these data are likely incomplete and probably are an underestimation of coverage.
According to the National Immunization Survey, as of February 3, 2024, coverage among adults
≥60 years of age was about 22.4%. Notably, the number who said they probably would get
vaccinated or were unsure has remained consistent over time. Looking at coverage by demographics based on monthly data using a Kaplan-Meier estimation procedure using all data
collected since September and including coverage as of the end of December 2023, coverage was slightly lower. By age group, coverage was lowest in adults 60─64 years of age and
highest in all age groups ≥65 years of age. Coverage was highest among White adults at
22.5% . Asian adults had similar coverage to White adults at 16.7%, but every other racial ethnic
group had lower coverage compared to White adults.
49

  For example, Black adults had about 10 percentage points lower coverage at 12.9% . Some
groups like NH/OPI had quite low coverage, which was 3.2%.
Adults ≥60 years with 1 or more chronic conditions had significantly higher RSV vaccination
coverage of about 25% than those with no chronic conditions at about 18 %. Each individual
chronic condition was elevated compared to people with no conditions, with the exception of
people with neurological conditions who had lower coverage compared to people with no conditions. Coverage decreased as the Social Vulnerability Index (SVI) of the county of
residence increased. Coverage was higher among people who received a n influenza vaccine for
the season or an updated COVID vaccine. Among people who received an influenza vaccine,
RSV coverage was about 30.5% and among those who had an updated COVID vaccine, RSV
coverage was 38.5%. Coverage also varied by region. Coverage was lower among people
residing in rural areas compared to those in urban and suburban areas. Coverage increased
with increasing income and with increasing education.
Regarding co-administration among adults ≥60 years of age, among those who received an
RSV vaccine , 57.1% received RSV alone, about 20% received RSV and influenza together,
about 15% received 3 vaccines together (RSV, Influenza, COVID) , and 8.5% received RSV and
COVID vaccine s together. The most recent data show that 84.4% of people were vaccinated in
a pharmacy compared to about 14% who were vaccinated in medical settings (e.g., physician
offices, hospitals, health departments , mass vaccination sites, and other medical settings ).
IQVIA data are based on medical claims from pharmacies and physicians practicing in medical offices. IQVIA uses a sample of claims from medical offices to project vaccinations given in all
medical offices in the US, which is based on a fairly small number of physicians. There is a lag
with the medical office data, which do not completely mature until about 2 months. The national
retail pharmacy data are a projection based on a much larger percentage of all pharmacies in
the US. Claims from pharmacies come in much faster, so there is higher confidence in the
completeness of the pharmacy data. None of the IQVIA data include vaccinations given in other medical settings such as public health clinics and hospitals, nor do they include vaccinations
given in non -medical settings. Therefore, it is known that this is not a complete assessment of
all RSV vaccines given in all settings in the US.
In terms of cumulative projected vaccines given to date in pharmacies and physician offices, a
combined total of 9.65 million RSV vaccinations were administered in retail pharmacies (9.36
million) and physician medical offices (291,599) as of February 3, 2024. An additional 164,254
RSV vaccinations were administered in long-term care pharmacies. Each week, the majority of
vaccines were the GSK product at about 69% compared to 31% of the Pfizer product. In
pharmacies, vaccinations peaked in about late October to early November and have been
declining since. Co-administration data from IQVIA showed similar patterns as in the NIS data
among all people who received RSV vaccine and other vaccines that were given on the same
day. About 52% received RSV only , about 22% received RSV and influenza vaccine, about 12%
received RSV and COVID vaccine, and approximately 13.5% received RSV, influenza, and
COVID vaccines together.
Using data from both NIS and IQVIA , the estimated range of persons vaccinated was
approximately 11– 18 million and estimated percent of persons vaccinated was 14%–22%.
50

 Transitioning to RSV v accination attitudes , data for this analysis were collected through the
IPSOS KnowledgePanel and NORC AmeriSpeak Omnibus Surveys, which use probability -
based panels to survey a nationally representative sample of US adults ≥18 years of age. CDC
fields questions about vaccination status, intent, knowledge, attitudes, beliefs, and behaviors on
each survey for 2 waves each month, for a combined sample size of approximately 4,000 respondents. Data were weighted to represent the non-institu tionalized US population and
mitigate possible non-response bias. All responses were self-reported. Among respondents who
reported that they received or definitely would get the vaccine, 84% reported no concerns or
issues. The top 3 reasons cited by those who expressed concerns were side effects (4.6%), not
having enough knowledge about RSV or the vacci ne (2.6%), and not having time (2.5%).
Among those who said they probably would get the vaccine or were unsure, about 35%
reported no concerns or issues. In this group, the top concerns cited were no HCP
recommendation (25.8%), do not know enough about RSV or the vaccine (23%), and the
vaccine is too new (11.8%). Of respondents who said they probably or definitely would not get the vaccine, about 26% reported that they had no concerns or issues. The top 3 concerns cited
among those who had concerns were not trusting the government or pharma (28.2%), not knowing enough about RSV or the vaccine (23%), and the vaccine is too new (21.2%). The most common concerns reported the previous day for COVID vaccines pertained to safety and
side effects, while for RSV vaccine it was more about lack of information and lack of provider
recommendation.
Regarding implementation considerations, there are a number of potential factors contributing to
relatively low vaccination coverage among people ≥60 years of age. As with any new vaccine, it
takes time to integrate into systems, gain wide access, increase awareness among HCP, and
normalize among the population. The 22% coverage seen for RSV vaccine is not out of line with
what has been observed with other new vaccines within the first year of introduction. Because
RSV is recommended based on shared clinical decision -making and the denominator for all of
these calculations was the population ≥60 years of age, not everybody ≥60 years of age is
actually expected to be vaccinated because it is not a universal recommendation. There are
several other issues with a shared clinical decision-making recommendation. There is feedback
from HCP that that having these conversations is not simple in practice, and they are confusing
for providers and patients compared with routine universal recommendations. Also, vaccines
are often administered by nurses, medical assistants , and pharmacists who are not always
comfortable with a shared clinical decision-making conversation or who do not feel like it is
within their scope of practice. In addition, these provider types often give vaccines under
standing orders, which are difficult with shared clinical decision-making and may not be allowed
in some states. People who do not have access to healthcare might not have a primary provider
with whom they can have a shared clinical decision-making discussion.  RSV vaccine is billed
under Medicare Part D unlike influenza and COVID vaccines, which results in billing issues in
provider offices. Vaccines are costly, meaning a costly upfront investment to carry the vaccine.
However, referral to a pharmacy means that a patient may be less likely to be vaccinated.
Residents of long-term care have additional, specific challenges.
Dr. Tom Shimabukuro (CDC/NCIRD) provided an update on CDC vaccine safety monitoring for
RSV vaccines in adults ≥60 years of age. In the pre-licensure studies for Pfizer among 20,255
vaccine recipients ≥60 year of age, 2 cases of GBS were observed within 42 days of
vaccination. In the pre-licensure studies for GSK among 18,304 recipients ≥60 years of age, 1
case of GBS was observed within 42 days of vaccination.
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 Due to the small number of GBS cases and the size of the pre-licensure studies, it is not known
at this time whether these GBS cases or other neuroinflammatory events occurred due to
random chance or whether RSV vaccination might increase the risk of these events. Post-
licensure safety monitoring of RSV vaccines is ongoing.
A new version of V -safe is now available that requires previous and new users to create an
account. It includes email and text messaging functionality. Including an email address is an
additional feature in this version of V -safe. Vaccines currently monitored include RSV vaccines
for older adults and pregnant persons and COVID vaccines for persons ≥6 months and older. V-
safe sends health surveys after vaccination daily during the first week and then weekly through
6 weeks. The daily surveys solicit local and systemic reactions and health impacts. T here are
additional questions for persons who reported immunocompromising conditions at vaccination. The weekly surveys solicit new symptoms or conditions after vaccination. Participants reporting
medically -attended health impacts are encouraged to complete a VAERS report.
In terms of the demographic characteristics for adults ≥60 years of age who reported RSV
vaccination from the early V-safe data, there were 15,745 registrants between October 20,
2023─ January 28, 2024 . Respondents were predominantly of White race and most participants
reported that their current state of health was excellent, very good, or good. Vaccines that were
commonly reported as co -administered with RSV vaccines were COVID -19 and influenza.
Reactions and health impacts reported for adults ≥60 years of age at least once during Day s
0─7 following vaccination by manufacturer, injection site reactions and systemic reactions were
fairly commonly reported. They were more commonly reported following the GSK vaccine in the
first week following vaccination than the Pfizer vaccine. As a reminder, the GSK vaccine
contains an adjuvant. A small number of individuals reported receiving medical care, which was
not necessarily tied to a vaccine AE.
VAERS is the nation’ s early warning system for vaccine safety. It is a spontaneous reporting or
passive surveillance system that is co-managed by CDC and FDA. The strengths of VAERS are
that it can rapidly detect safety signals and can detect rare AEs. As a spontaneous reporting
system, the main limitation of VAERS is that it is not designed to assess causality. VAERS
accepts all reports from all reporters without making judgements on causality or judging the
clinical seriousness of the event. As a hypothesis -generating system, VAERS identifies potential
vaccine safety concerns that can be studied in more robust data systems. For all vaccines,
signs and symptoms of AEs are coded using the Medical Dictionary for Regulatory Activities
(MedDRA) Preferred Terms (PTs). MedDRA PTs are not mutually exclusive, so a single report
may be assigned more than 1 MedDRA PT. Reports of SAEs were individually reviewed along
with accompanying medical records if available. Brighton Collaboration Case Definitions were
applied for neuroinflammatory conditions, GBS, and ADEM. Reporting rate calculations used doses of vaccine administered for each type of RSV vaccine. Empirical Bayesian data mining
was conducted by FDA to detect disproportional reporting for the entire post-marketing period
for each product.
A number of AESIs that are currently being monitored for RSV vaccination include death,
Guillain -Barré syndrome, acute disseminated encephalomyelitis, transverse myelitis, chronic
inflammatory demyelinating polyneuropathy, anaphylaxis, atrial fibrillation, other
supraventricular tachycardia, optic neuritis, multiple sclerosis, Bell’s palsy,
encephalitis/encephalomyelitis, meningitis/meningoencephalitis, myelitis, vaccination errors, and adverse events following simultaneous administration with COVID -19, inactivated influenza, or
other adult vaccines.
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  As of February 16, 2024 , there were 3,689 total reports to VAERS after RSV vaccines, which
was after approximately 9.6 million doses administered. The total number of reports for the 2
products was 2,516 for GSK and 1,045 for Pfizer, which track s closely with the doses
administered. The median age, female proportion, and serious and non- serious proportions
were similar between the 2 vaccines and similar to what is seen with other vaccines
administered among adults ≥60 years of age. Looking at the most frequently reported MedDRA -
preferred terms in adults ≥60 years of age broken down by manufacturer , for both the Pfizer and
the GSK vaccines, the most commonly reported symptoms were local and systemic reactions.
The safety profile for these most commonly reported symptoms for the 2 vaccines were similar .
MedDRA -preferred terms of the reports by non-serious and serious status , non-serious reports
dominated and was similar to local and systemic reactions. Some of the serious reports were
general conditions like asthenia, fatigue, gait disturbance, muscular weakness , and GBS.
On January 19, 2024, a data mining alert for disproportional reporting was detected in FDA ’s
Empirical Bayesian data mining for the Pfizer vaccine and GBS. No data mining alert for the GSK vaccine and GBS has been detected to date. Empirical Bayesian data mining is product-specific and analyzes product-specific VE event pairings compared to the overall VAERS
database. A total of 37 preliminary reports were received as of February 16, 2024. Of these, 6
are currently under review , 7 were excluded based on medical record review, and 1 was verified
but was excluded due to onset after 42 days. This left 23 verified GBS reports by medical record
review , of which 15 were after the Pfizer vaccine and 8 were after GSK vaccine. The median
age in these reports was 71 years , with an interquartile range of 63─ 75 years of age. There was
1 report in a non-pregnant female in her 50s who received Pfizer. T hat vaccine was either given
off-label or in error.
The median time to onset was 9 days, with a range 1─ 22 days. There were 14 males and 9
females, none of whom were pregnant. There was 1 death in a male patient in his 70s who
received the GSK vaccine. All 23 verified reports met Brighton Collaboration criteria for GBS
comprised of 3 Brighton Level 1, 12 Level 2, 8 Level 3. Brighton Level 1 is the highest level of
diagnostic certainty. Level 4 or 5 are not considered cases. Commonly administered vaccines
were COVID -19 vaccines and influenza vaccines.
The reporting rate in the 21-day risk window was 4.6 reports per million doses administered for
the Pfizer vaccine and 1.1 reports per million doses administered for the GSK vaccine. For the
42-day risk window , the reporting rate was the same for Pfizer because all of those cases had
onset within 21 days. There was 1 case with a 22-day onset. For the 42-day risk window, there
were 4.6 reports per million doses administered for the Pfizer vaccine and 1.2 reports per million
doses administered for the GSK vaccine. Putting the observed reporting rates into the context of
what would be expected can be challenging with VAERS data passive surveillance. The chart-confirmed rate of GBS after mRNA COVID -19 vaccination in the VSD was used as a proxy for
background rate. To be clear upfront, safety monitoring of the mRNA COVID-19 vaccines in
VSD did not detect an increased risk of GBS associated with either of the mRNA COVID -19
vaccines. Therefore, the rate of GBS following mRNA COVID -19 vaccination can be used as a
proxy for the background rate of GBS in a vaccine -accepting population.
This rate is appropriate because it is a relatively current rate within the past several years. This
is primarily monovalent mRNA vaccination. All of these cases were a priori chart-reviewed during the normal process of VSD surveillance for mRNA COVID -19 vaccines. There are some
limitations with this method (e.g., different populations, different time periods, different age groups) .
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  The estimated rate of GBS in adults ≥65 years of age following mRNA COVID-19 vaccines
primary series in VSD in the 21-day risk interval was 3.4 per 100,000 person years and in the
42-day risk interval was 4.5 per 100,000 person years. Again, because the mRNA COVID -19
vaccines are not associated with an increased risk of GBS, this can be considered the
background incidence of GBS in a vaccine-accepting population. When that is converted to per
million doses in the 21-day risk interval, the expected cases per 1 million RSV doses
administered would be 2 cases per million doses administered with a range from the 95%
confidence interval of 0.7─ 4.2. For the 42-day risk interval, the expected cases per 1 million
RSV doses administered would be 5.2 cases per million doses administered with a range from
the 95% confidence interval of 2.8─ 8.9.
Returning to the observed VAERS reporting rates after RSV vaccination among adults ≥60
years of age compared to the expected rate per million doses administered, in the 21 -day risk
interval for the Pfizer vaccine, the VAERS reporting rate was 4.6 per million doses administered and the expected rate based on VSD data would be 2 per million doses administered with the
upper bound of the confidence interval at 4.2. That point estimate for the reporting rate was
elevated for the Pfizer vaccine. For the GSK vaccine, reporting rates after RSV vaccination
among adults ≥60 years of age compared to the expected rate per million doses administered in
the 21-day risk interval for the GSK vaccine was 1.1 per million doses administered compared
to the expected rate of 2.0. That falls within the 95% confidence interval. For the 42-day risk
window for the Pfizer for 4.6 per million doses administered, the estimated expected rate based
on VSD data would be 5.2 with a confidence interval of 2.8 ─8.9. For the GSK vaccine, it
increased to 1.2 per million doses administered because of the extra case at 22 days. The
reporting rate was not elevated when compared to the background in VSD. The caveat is that
there is known to be underreporting in VAERS, so the observed VAERS reporting rates are
likely an underestimate of the true rate.
The VSD is CDC’s active surveillance system used for R apid Cycle Analysis (RCA) and
research that was established in 1990. It has about 13.5 million individuals across the sites ,
including about 2.8 million adults ≥60 years of age. Looking at the observed VSD GBS rates
following RSV vaccination in adults ≥60 years of age through December 30, 2023, the VSD
identified 4 GBS cases within 1─ 84 days of receipt of the GSK vaccine. All 4 cases under went
medical record review and were adjudicated. The rates for the GSK vaccine were 9.5 per million
doses administered 21-day risk window and 14.3 per million doses administered in the 42-day
risk window. Qualitatively, these rates were higher than rates observed for high-dose influenza
and Shingrix. The caveat is that these are very early data based on a small number of cases
and a small number of doses administered. The 4
th case was not included because it was
classified as Level 4 and is pending additional review. Currently, no cases of GBS have been
observed after the Pfizer vaccination, but only about 10% of all vaccinations in the VSD have
been with Pfizer. The VSD will continue to monitor the safety of RSV vaccines in adults ≥60
years of age . Formal sequential safety analys es will begin March 2024 using a vaccinated
concurrent comparison group, which is similar to what was done for COVID.
To summarize, local and systemic symptoms were the most commonly reported AEs following
either of the RSV vaccines. Monitoring in VAERS indicated a higher -than-expected number of
GBS reports following the Pfizer vaccine, but VAERS is subject to the limitations of passive
surveillance. GBS cases were observed in the pre -licensure clinical trials for both the Pfizer and
the GSK vaccines. GBS is included as an AE in the labels of both vaccines. Early data from
VSD suggests a potential for an increased rate for GBS after the GSK vaccine, but additional
analys es are needed to further assess this potential risk. Insufficient doses of the Pfizer vaccine
have been used in VSD to inform risk.
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Summary: MEETING OF THE ADVISORY  COMMITTEE ON IMMUNIZATION  PRACTICES (ACIP)  FEBRUARY 28-29, 2024  MEETING SUMMARY  Trade names are used for identification purposes only and do not indicate endorsement.                                                                                WEDNESDAY: FEBRUARY 28, 2024  WELCOME AND INTRODUCTIONS  Call to Order/Roll Call  Dr. Melinda Wharton (ACIP Executive Secretary & Acting Chair ,…