06 COVID Wallace 508

Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
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Evidence to Recommendations Framework:
Additional Dose of 2023-2024 Formula COVID -19 Vaccine in Older Adults
Megan Wallace, DrPH, MPH
ACIP Meeting February 28, 2024
Should persons ages 65 years and older be recommended for an additional dose of
2023- 2024 Formula COVID -19 vaccine?
–Additional dose should be at least 4 months after previous updated (2023 -2024)
COVID -19 vaccine dose.
Authorized and approved 2023 -2024 Formula COVID -19 vaccines:
–Moderna COVID -19 vaccine
–Novavax COVID -19 vaccine
–Pfizer -BioNTech COVID -19 vaccineEvidence to Recommendations (EtR) Framework
Policy Question
2
3Timeline of additional dose recommendations
Sept – Nov 2021 COVID -19 vaccine
booster doses
recommended
for persons ages
≥18 years
May 2022 Additional COVID -19
vaccine booster dose
recommended for
persons ages ≥50 years
(should  recommendation)
Sept – Oct 2022 Bivalent COVID -19
vaccine dose
recommended for
persons ages ≥5
years
April 2023 Optional additional
bivalent COVID -19
vaccine dose
recommended for
persons ages ≥65 years
(may  recommendation)
Sept 20232023- 2024 COVID -
19 vaccine doses
recommended for
persons ages ≥6
months
People who are moderately or severely immunocompromised:
Have the option to receive 1 additional dose of updated (2023 -2024 Formula) COVID -
19 Vaccine at least 2 months following the last recommended updated (2023 -2024
Formula) COVID -19 vaccine dose.
Further additional dose(s) may be administered, informed by the clinical judgement of
a healthcare provider and personal preference and circumstances. Any further additional doses should be administered at least 2 months after the last updated (2023- 2024 Formula) COVID -19 vaccine dose.Current recommendations for additional doses of updated
(2023 -2024 Formula) COVID- 19 vaccine
Note: Children aged 6 months –4 years need multiple doses of COVID -19 vaccines to be up to date, including at least 1 dose of updated COVID -19 vaccine. 4
EtR Domain:
Public Health Problem

66Weekly number of COVID -19 hospitalizations, United States,
January 1, 2023 – February 17, 2024
CDC COVID Data Tracker. National Healthcare Safety Network (NHSN). https://covid.cdc.gov/covid -data -tracker/#trends_weeklyhospitaladmissions_select_00 . Accessed February
23, 2024

77Weekly population -based rates of COVID -19-associated
hospitalizations, by age group  —  COVID -NET , January 1, 2023 –
February 24, 2024
Dashed lines indicate potential reporting delays and interpretation of trends should exclude these weeks.
CDC COVID Data Tracker. https://covid.cdc.gov/covid -data -tracker/#covidnet -hospitalization -network . Accessed February 23, 2024

88Weekly population- based rates of COVID -19-associated
hospitalization among adults ages ≥65 years, by age group—
COVID -NET, January 1, 2023 – January 27, 2024
Thin dashed lines on the far right indicate potential reporting delays and interpretation of trends should exclude these week s.
CDC COVID Data Tracker. https://covid.cdc.gov/covid -data -tracker/#covidnet -hospitalization -network . Accessed February 6, 2024

99Weekly number of provisional COVID -19 deaths reported to
CDC, United States, January 1, 2023 – February 17, 2024
The most recent 3 weeks of mortality counts are shaded grey because NVSS reporting is <95% during this period.
Provisional data are non -final counts of deaths based on reported mortality data in NVSS. Deaths include those with COVID- 19, coded as ICD– 10 code U07.1, on the death certificate.
Death data are displayed by date of death (event).
CDC COVID Data Tracker. National Center for Health Statistics (NCHS) National Vital Statistics System (NVSS). https://covid.cdc.gov/covid- data -tracker/#trends_weeklydeaths_select_00 .
Accessed February 23, 2024

1010Monthly rates of provisional COVID -19 deaths by age group,
United States, January 1, 2023 – January 31, 2024
Provisional data are non -final counts of deaths based on reported mortality data in NVSS. Deaths include those with COVID- 19, coded as ICD– 10 code U07.1, on the death certificate.
Death data are displayed by date of death (event).
Source: Provisional data from the CDC’s National Center for Health Statistics (NCHS) National Vital Statistic System (NVSS); CDC COVID Data Tracker. https://covid.cdc.gov/covid- data -
tracker/#demographicsovertime . Accessed February 23, 2024

1111Weighted U.S. SARS -CoV-2 seroprevalence by vaccine and
infection history and age, based on blood donations
Seroprevalence definition: The percentage of people with antibodies against a virus in their blood is known as seroprevalence .
Methodology available at https://covid.cdc.gov/covid- data -tracker/#nationwide -blood -donor -seroprevalence -2022 9
14
2635
26
1454
59
581
2
2
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%30 to 49 years
50 to 64 years
65 years and olderJuly 1st – September 30th, 2023
Vaccination-only seroprevalence Infection-only seroprevalence
Hybrid Immunity Neither past infection nor vaccination
1212Pool of naïve T cells diminishes with age
Source: de Candia P , Prattichizzo  F, Garavelli S, Matarese G. T Cells: Warriors of SARS- CoV-2 Infection. Trends Immunol. 2021 Jan;42(1):18- 30. doi: 10.1016/j.it.2020.11.002.
Epub 2020 Nov 13. PMID: 33277181; PMCID: PMC7664351Immunosenescence  refers to  age-associated immune decline that may result in an inefficient immune response to
novel antigens and an inability to develop proper immunity against infections and upon vaccination.
1313Adaptive immunity includes cellular and humoral responses
Source: Rey, Gertrud.  T Cell Responses to Coronavirus Infection are Complicated. https://www.virology.ws/2020/11/05/t -cell-responses -to-coronavirus -infection -are-complicated/Insufficient pools of naïve T
cells impacts ability to generate:
•Neutralizing antibody responses
•Cytotoxic T cells
1414Weekly percent of tests positive for COVID -19, Influenza, and
RSV, United States, October 1, 2022 – February 17, 2024
Preliminary data are shaded in gray.
Sources: COVID -19 and RSV: National Respiratory and Enteric Virus Surveillance System (NREVSS), a sentinel network of laboratori es located through the US, includes clinical, public health
and commercial laboratories; additional information available at: https://www.cdc.gov/surveillance/nrevss/index.html. Influen za: Clinical laboratory test results from NREVSS and U.S. World
Health Organization collaborating laboratories; more details about influenza virologic surveillance are available here: https:// www.cdc.gov/flu/weekly/overview.htm.
CDC Respiratory Virus Activity Levels. https://www.cdc.gov/respiratory -viruses/data -research/dashboard/activity -levels.html . Accessed February 6, 2024

1515
Weekly hospitalization rate per 100,000 population, United
States, October 1, 2022 – February 17, 2024
Preliminary data are shaded in gray.
Dashed line represents the nadir for COVID- 19 hospitalization rates.
CDC Respiratory Virus Activity Levels. National Healthcare Safety Network. https://www.cdc.gov/respiratory -viruses/data -research/dashboard/illness -severity.html. Accessed
February 23, 2024

Domain Equity Question:
Does the problem impact all populations equally?

1717Age-adjusted cumulative COVID -19 hospitalizations per 100,000
population by race and ethnicity  — COVID -NET , October 2022 –
September 2023
CDC COVID Data Tracker. https://covid.cdc.gov/covid -data -tracker/#covidnet -hospitalization -network . Accessed February 23, 2024

1818Number of chronic conditions by age among Asian, Black, Latino/Hispanic,
and White adults in the National Health Interview Survey, 1999 to 2018
Source: Caraballo C, Herrin J,
Mahajan S, et al. Temporal Trends in
Racial and Ethnic Disparities in Multimorbidity Prevalence in the United States, 1999 -2018. Am J Med .
2022;135(9):1083- 1092.e14.
doi:10.1016/j.amjmed.2022.04.010

COVID -19 hospitalizations peaked in late December/early January, however there are still
approximately 20,000 new hospital admissions and 2,000 deaths due to COVID -19 each week.
Persons ages ≥65 years have the highest COVID -19 hospitalization rates.
–Hospitalization rates within this age group increase with increasing age.
Persons ages ≥75 years 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.Summary
Public Health Problem
19
Public Health Problem
Work Group Interpretation
Is COVID -19 disease among persons ages 65 years and older of public health
importance?
oNooProbably no oProbably yes oYesoVaries oDon’t know
EtR Domain:
Benefits and Harms

Updated (2023- 2024) 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.
Receipt of updated (2023 -2024) COVID -19 vaccine provides protection against JN.1 and
other circulating variants.
These early vaccine effectiveness estimates show no substantial waning; however,
waning is expected.2023 -2024 Formula COVID- 19 vaccine effectiveness
ED: Emergency department | UC: Urgent care 22
23VISION: Absolute  VE of original  monovalent  and bivalent  booster doses
against hospitalization among immuno competent  adults, by age group –
September 2022 – August 2023
VE estimates adjusted for age, sex, race and ethnicity, geographic region, and calendar time. Updated from: Link -Gelles et al., MMWR, https://www.cdc.gov/mmwr/volumes/72/wr/mm7221a3.htm
* These estimates are imprecise, which might be due to there being a relatively small number of persons in each level of vacc ination or case status. This imprecision indicates that the actual VE
could be substantially different from the point estimate shown, and estimates should therefore be interpreted with caution. A dditional data accrual could increase precision and allow more precise
interpretation.mRNA Dosage PatternTotal
testsSARS -CoV -2-
test -positive,
N (%)Median interval
since last dose,
days (IQR)Adjusted VE
(95% CI)
18-64 years
Unvaccinated (ref) 13,089 803 (6) -- Ref
Original monovalent  doses only 19,799 1,129 (6) 455 (333 -575) 15 (6 to 23)
Bivalent  booster, 7 -59 days earlier 1,208 45 (4) 33 (21 -45) 61 (46 to 71)
Bivalent  booster, 60- 119 days earlier 1,248 87 (7) 87 (73 -102) 15 (-8 to 33)
Bivalent  booster, 120- 179 days earlier 1,075 59 (6) 147 (134 -163) -1 (-35 to 24)*
≥65 years
Unvaccinated (ref) 12,015 1,688 (14) -- Ref
Original monovalent  doses only 37,001 4,216 (11) 402 (288 -555) 25 (20 -30)
Bivalent  booster, 7 -59 days earlier 4,607 328 (7) 35 (21- 48) 67 (62 -71)
Bivalent  booster, 60- 119 days earlier 5,252 490 (9) 88 (73 -104) 53 (48 -58)
Bivalent  booster, 120- 179 days earlier 4,482 415 (9) 149 (134 -164) 28 (18 -36)
-40 -20 0 20 40 60 80 100
Vaccine  Effectiveness (%)
24VISION: Absolute  VE of original  monovalent  and bivalent  booster doses
against hospitalization and critical illness among immuno competent  adults
aged ≥18 years – September 2022 – August 2023
Critical illness defined as admission to intensive care unit or death; case -patients were persons admitted to ICU or who experie nced death associated with COVID -19, and control
patients were persons hospitalized without COVID -19. VE estimates adjusted for age, sex, race and ethnicity, geographic region, and calendar time. Updated from: Link -Gelles et
al., MMWR, https://www.cdc.gov/mmwr/volumes/72/wr/mm7221a3.htm  mRNA Dosage PatternTotal
testsSARS -CoV -2-
test -positive,
N (%)Median interval
since last dose,
days (IQR)Adjusted VE
(95% CI)
Hospitalization
Unvaccinated (ref) 25,104 2,491 (10) -- Ref
Original monovalent  doses only 56,800 5,345 (9) 420 (306 -563) 22 (17- 26)
Bivalent  booster, 7 -59 days earlier 5,815 373 (6) 34 (21 -47) 65 (61 -69)
Bivalent  booster, 60- 119 days earlier 6,500 577 (9) 87 (73 -103) 48 (42 -53)
Bivalent  booster, 120- 179 days earlier 5,557 474 (9) 149 (134 -164) 22 (13- 30)
Critical illness
Unvaccinated (ref) 23,140 527 (2) -- Ref
Original monovalent  doses only 52,352 897 (2) 422 (306 -564) 32 (23- 40)
Bivalent  booster, 7 -59 days earlier 5,504 62 (1) 34 (21 -47) 69 (59 -77)
Bivalent  booster, 60- 119 days earlier 6,023 100 (2) 87 (73 -103) 50 (36 -60)
Bivalent  booster, 120- 179 days earlier 5,144 61 (1) 149 (134 -164) 46 (28 -60)
-20 0 20 40 60 80 100
Vaccine  Effectiveness (%)
No clinical trial immunogenicity data of an additional dose of 2023 -2024 COVID -19 vaccine.
Initial dose of 2023 -2024 COVID -19 vaccine elicits robust neutralizing antibodies and provides
protection against JN.1 and other circulating variants.1,2
Effectiveness of an additional dose in older adults has been demonstrated by past additional
doses
–Among adults aged ≥50 years eligible to receive a second original monovalent mRNA COVID- 19
vaccine booster dose, VE for COVID- 19–associated ED/UC encounters during the BA.2/BA.2.12.1
period was 32% at ≥120 days after the third dose but increased to 66% ≥7 days after the fourth dose.
VE against COVID -19–associated hospitalization was 55% ≥120 days after the third dose but increased
to 80% ≥7 days after the fourth dose.3
–In a large cohort of nursing home residents, r eceipt of a second original monovalent mRNA COVID -19
booster dose during circulation of SARS- CoV-2 Omicron subvariants was 74% effective at 60 days
against severe COVID -19–related outcomes (including hospitalization or death) and 90% against death
alone compared with receipt of a single booster dose.4Effectiveness of an additional dose of COVID -19 vaccine
1.https://www.biorxiv.org/content/10.1101/2023.11.26.568730v2
2.https://www.cdc.gov/mmwr/volumes/73/wr/mm7304a2.htm
3.https://www.cdc.gov/mmwr/volumes/71/wr/mm7129e1.htm
4.https://www.cdc.gov/mmwr/volumes/71/wr/mm7139a2.htm  25
26Microsimulation modeling study compares frequency of
COVID -19 vaccine by risk group
https://www.medrxiv.org/content/10.1101/2023.07.10.23292473v4
HJ Park…NC Lo. Accepted at Nature Communications (2024) .Step 1 : Assign to risk group
•Age group: 18-49, 50- 64, 65- 74, 75+ years
•Immune status: immunocompetent,
immunocompromised (mild, moderate/severe)Step 3 : Calibrate model to data
•Epidemiologic data: COVID -19 severe incidence, seroprevalence
•Calibrated to ~September 2022
Computer
simulation
Step 2 : Simulate vaccine -induced or hybrid protection
•Vaccine: number doses, timing of last dose
•Prior infection: yes/no, timing of last infection
•Vaccine/hybrid protection data: level of protection and waning curves Step 4 : Run simulation of different vaccine strategies
•Vaccine strategies: One -time (1 dose); Annual (2 doses), Semi -annual (4
doses); Simulate over 2 -years
•Simulate person- level waning of protection and COVID -19 at each time step
(static infection model)
•Primary study outcome: Absolute annual risk of severe COVID -19
3 Month
06 1

27Annual and semiannual COVID -19 vaccine doses likely to have largest benefit
in people ages ≥65 years and people who are immunocompromised
Absolute annual risk of
severe COVID -19
(cases per 100,000;
uncertainty interval)Annual risk reduction of severe
COVID -19 NNT to avert
severe
COVID -19 case Absolute risk (cases
per 100,000)Relative risk
(%)
One -time booster
18-49 years 98 (85 -  125) -- -- --
50-64 years 199 (185 -  238) -- -- --
65-74 years 524 (499 -  562) -- -- --
75+ years 1,398 (1,332 -  1,501) -- -- --
Immunocompromised (mild) 1,290 (1,205 –  1,403) -- -- --
Immunocompromised (moderate/severe) 1,367 (1,266- 1,503) -- -- --
Annual booster
18-49 years 84 (74 -  106) 14 14% 3,534
50-64 years 171 (159 -  202) 28 14% 1,806
65-74 years 446 (425 -  475) 78 15% 642
75+ years 1,198 (1,144 -  1,272) 199 14% 251
Immunocompromised (mild) 1,180 (1,088 -  1,316) 110 9% 456
Immunocompromised (moderate/severe) 1,183 (1,091- 1,307) 184 13% 273
Semiannual booster (every 6 months)
18-49 years 72 (64 -  90) 26 27% 1,916
50-64 years 147 (136 -  171) 52 26% 968
65-74 years 382 (365- 404) 142 27% 353
75+ years 1,030 (988 -  1,088) 368 26% 136
Immunocompromised (mild) 1,095 (987 -  1,255) 195 15% 257
Immunocompromised (moderate/severe) 1,057 (966- 1,183) 310 23% 162
https://www.medrxiv.org/content/10.1101/2023.07.10.23292473v4
HJ Park…NC Lo. Accepted at Nature Communications (2024) .NNT: number of persons needed to follow vaccine strategy
to prevent one severe COVID -19 case over 2- year period
Severe COVID -19 case: defined as being hospitalized
28COVID -19 vaccines have a favorable safety profile as demonstrated by robust safety
surveillance over 3 years of COVID -19 vaccine use.
–Anaphylactic reactions have been rarely reported following receipt of COVID -19 vaccines.
–Rare risk of myocarditis and pericarditis, however this is predominately in males ages 12 -39
years.
–No new safety concerns have been identified for the 2023 -2024 Formula COVID -19 vaccine.
Reactogenicity symptoms have been reported following COVID -19 vaccines.
–Local: Pain at the injection site; less commonly, redness and swelling at the injection site
–Systemic: Fever, fatigue, headache, chills, myalgia, arthralgia, and diarrhea
–Overall, symptoms less frequent and severe among older adults compared with adolescents
and younger adults.COVID -19 vaccine safety
29A statistical signal for ischemic stroke after Pfizer- BioNTech bivalent mRNA COVID -19
vaccine was detected in CDC’s Vaccine Safety Datalink in persons aged ≥65 years during
fall 2022; information was presented at prior ACIP meetings and efforts have been underway to evaluate the signal.
2
Available data do not provide clear and consistent evidence of a safety problem for ischemic stroke with bivalent mRNA COVID -19 vaccines when given alone or given
simultaneously with influenza vaccines.
–Variable and inconsistent results were obtained in some analyses of the risk of ischemic
stroke following bivalent mRNA COVID -19 vaccination, simultaneous bivalent mRNA COVID -
19 and influenza vaccination, and influenza vaccination alone.
–Most study results have not shown an association between vaccination and ischemic stroke, and no clear pattern demonstrating increased risk has emerged.Review of COVID -19 vaccine and ischemic stroke1
1https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2023- 10-25-26/01- VaxSafety -Shimabukuro -508.pdf
2 https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2023- 02/slides -02-24/COVID -02-Shimabukuro -508.pdf  and
https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2023- 04-19/03- COVID -Shimabukuro -508.pdf
30Any real or theoretical risk needs to be placed in the context of the known benefits of
COVID -19 vaccination in preventing COVID- 19 disease and the potentially serious
complications, including stroke.
Among adults aged ≥65 years, a recent bivalent mRNA COVID -19 vaccine dose helped
provide protection against COVID- 19-related thromboembolic events compared with
more distant receipt of original monovalent doses alone.1Review of COVID -19 vaccine and ischemic stroke
1. https://www.cdc.gov/mmwr/volumes/73/wr/mm7301a4.htm
Domain Equity Question:
Are the desirable and undesirable anticipated effects
demonstrated across all populations equally?

There is no evidence to suggest that COVID- 19 vaccine effectiveness varies substantially
by race/ethnicity.1,2
–Differences in vaccine hesitancy/uptake, crowding, access to care, and prior infection could
impact vaccine effectiveness and these factors may also differ by race/ethnicity.
There is no evidence to suggest that COVID- 19 vaccine safety profiles vary by
race/ethnicity, however risk has been shown to differ by age and sex.
–Risk for myocarditis is highest in adolescent and young adult males.
Benefits and harms for the U.S. population are best assessed when clinical trial and
study populations are optimally representative of the U.S. population. Are the desirable and undesirable anticipated effects
demonstrated across all populations equally?
1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9619452/
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9763212/  32
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 vaccine effectiveness from previous vaccine formulations has waned over time but
appears more durable against critical illness.
An additional dose of 2023 -2024 Formula may restore vaccine effectiveness 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.
–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 given
simultaneously with influenza vaccines.Summary
Benefits and Harms
33
Benefits and Harms
How substantial are the desirable anticipated effects?
•How substantial are the anticipated effects for each main outcome for which
there is a desirable effect?
oMinimal oSmall oModerate oLarge oVaries oDon’t know
Benefits and Harms
How substantial are the undesirable anticipated effects?
•How substantial are the anticipated effects for each main outcome for which
there is an undesirable effect?
oMinimal oSmall oModerate oLarge oVaries oDon’t know
Minority opinion  Majority opinion
Benefits and Harms
Do the desirable effects outweigh the undesirable effects?
•What is the balance between the desirable effects relative to the
undesirable effects?
oFavors intervention (Additional dose of 2023-2024 Formula COVID -19 vaccine)
oFavors comparison (no vaccine)
oFavors both
oFavors neither
oUnclear
EtR Domain:
Values

3838Key attitudes and experiences among adults 18 years and older, December 2023
National Immunization Survey -Adult COVID Module (NIS -ACM)
The December estimates are based on data collected November 26 through December 30.
CDC. COVID -19 Vaccination Coverage and Vaccine Confidence Among Adults. https://www.cdc.gov/vaccines/imz -managers/coverage/covidvaxview/interactive/adults.html
Accessed February 7, 2024COVID -19 Vaccination Key Attitudes and Experiences by Age Group
Among Adults Age ≥18 Years, NIS -ACM, December 2023
Adults ages 65 years and older were more
concerned about COVID -19 disease and had
higher confidence in vaccine safety and
vaccine importance; those ages 18 – 49 years
and 50 – 64 years were less concerned and
confident.265365
355367
416578
0102030405060708090
Concerned about COVID-19 disease Confidence in COVID-19 vaccine safety Confidence that COVID-19 vaccine is
somewhat or very important to protect
mePercent
18 - 49 years 50 - 64 years 65+ years
3939Half of adults say they are taking precautions because of
COVID -19 during the fall and winter months
The survey was conducted October 31 - November 7, 2023, online and by telephone among a nationally representative sample of 1,301  U.S. adults.
KFF COVID -19 Vaccine Monitor (Oct. 31- Nov. 7, 2023) KFF COVID -19 Vaccine Monitor November 2023: With COVID Concerns Lagging, Most People Have Not Gotten Latest Vaccine
And Half Say They Are Not Taking Precautions This Holiday Season | KFF  Accessed November 17, 2023501819253035
0 10 20 30 40 50 60 70 80 90 100Any of these precautionsTaking a COVID-19 test before visiting with friends or familyAvoiding dining indoors at restaurantsAvoiding travelWearing a mask in crowded placesAvoiding large gatherings
PercentPercent who say they are taking each of the following precautions because of
COVID -19 this fall and winter:
40Similar shares of younger and older adults reported plans to take at least one
precaution during the fall and winter.
However, four in ten ( 41% ) adults ages 65 and older said they plan to avoid large
gatherings, compared to a third ( 33% ) of those under the age of 65.
While younger adults were less likely to say they will avoid large gatherings, 21%  of
those <65 years say they will take a test for COVID -19 before spending time with friends
or family compared to 10%  of those ages 65 and older.Precautions against COVID -19 during fall and winter by age
The survey was conducted October 31 - November 7, 2023, online and by telephone among a nationally representative sample of 1,301  U.S. adults.
KFF COVID -19 Vaccine Monitor (Oct. 31- Nov. 7, 2023) KFF COVID -19 Vaccine Monitor November 2023: With COVID Concerns Lagging, Most People Have Not Gotten Latest Vaccine
And Half Say They Are Not Taking Precautions This Holiday Season | KFF  Accessed November 17, 2023
Domain Equity Question:
Is there important variability in how patients or
populations value the outcome?

4242Key attitudes and experiences among adults 18 years and older, December 2023
National Immunization Survey -Adult COVID Module (NIS -ACM)
AI/AN: American Indian or Alaska Native; NH/PI: Native Hawaiian or Other Pacific Islander
The December estimates are based on data collected November 26 through December 30.
CDC. COVID -19 Vaccination Coverage and Vaccine Confidence Among Adults. https://www.cdc.gov/vaccines/imz -managers/coverage/covidvaxview/interactive/adults.html
Accessed February 7, 2024COVID -19 Vaccination Key Attitudes and Experiences by Race & Ethnicity
Among Adults Age ≥18 Years, NIS -ACM, December 2023
295573
305765
415078
347185
334967
313354
304757
0102030405060708090
Concerned about COVID-19 disease Confidence in COVID-19 vaccine safety Confidence that COVID-19 vaccine is
somewhat or very important to protect
mePercent
Hispanic White, non-Hispanic Black, non-Hispanic
Asian, non-Hispanic NH/PI, non-Hispanic AI/AN, non-Hispanic
Other or multiple races, non-Hispanic
4343Precautions against COVID -19 during fall and winter by race
and ethnicity
The survey was conducted October 31 - November 7, 2023, online and by telephone among a nationally representative sample of 1,301  U.S. adults.
KFF COVID -19 Vaccine Monitor (Oct. 31- Nov. 7, 2023) KFF COVID -19 Vaccine Monitor November 2023: With COVID Concerns Lagging, Most People Have Not Gotten Latest Vaccine
And Half Say They Are Not Taking Precautions This Holiday Season | KFF  Accessed November 17, 2023391312171727
682436434749
723433365953
0 10 20 30 40 50 60 70 80 90 100Any of these precuationsTaking a COVID-19 test before visiting with friends or familyAvoiding dining indoors at restaurantsAvoiding travelWearing a mask in crowded placesAvoiding large gatherings
PercentPercent who say they are taking each of the following precautions because of
COVID -19 this fall and winter:
Black Hispanic White
Adults ages 65 years and older were more concerned about COVID- 19 disease and had
higher confidence in vaccine safety and vaccine importance than those <65 years.
–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 racial and ethnic group.
Half of adults reported plans to take precautions because of COVID- 19 during the fall
and winter months, with 41% of adults ages ≥65 years planning to avoid large
gatherings.
–Larger proportions of Black and Hispanic adults report they plan to take precautions against
COVID -19 than White adults. Summary
Values
44
Values
Criteria 1:
Do older adults feel that the desirable effects are large relative to undesirable
effects?
•How do older adults view the balance of desirable versus undesirable effects?
•Would older adults feel that the benefits outweigh the harms?
oMinimal oSmall oModerate oLarge oVaries oDon’t know
Values
Criteria 2:
Is there important uncertainty about, or variability in, how older adults value
the main outcomes?
•Is there evidence that the variability is large enough to lead to different decisions?
oImportant uncertainty or variability
oProbably important uncertainty or variability
oProbably not important uncertainty or variability
oNo important uncertainty or variability
oNo known undesirable outcomesMajority opinion
Minority opinion
EtR Domain:
Acceptability

4848Percent vaccinated with 2023 -24 COVID- 19 vaccine
National Immunization Survey -Adult COVID Module (NIS -ACM)
COVID -19 Vaccination Coverage with 2023- 24 Vaccine
Among Adults ≥18 Years, NIS- ACM
0.010.020.030.040.050.0Vaccinated with 2023 -24 COVID -19 vaccine (%)
Week end dateAll adults 18+
75+
65-74
50-64
40-49
30-39
18-29
4949Top COVID -19 vaccination concerns and issues among adults ≥65 years of
age, by status/intent, Omnibus Surveys, January 5 – 29, 2024 (N=882)
Other response options included: "Too busy or kept forgetting," "Cost/time concerns," "Unsure if eligible," "Fertility issues ," "HCP recommended against," "Other concern."
*Option not offered to those who already received the vaccine.
Omnibus Surveys: 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 U.S. adults aged 18
years and older. 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 ~4,000 respondents. These slides present results
from January (N=4,287). Data were weighted to represent the non -institutionalized U.S. population and mitigate possible non- resp onse bias. All responses are self -reported. 6.1%
5.5%
5.0%
2.8%
2.7%
2.6%
1.3%
1.2%
0 25 50 75 100Effectiveness
Unknown serious
side effects
Mild side
effects
Do not trust
gov. or pharma
Not enough studies
(human trials)
Heart -related
issues
Hard to get
appointment
Impact of side effects
on work/school
Weighted % (95% confidence interval)Received/definitely wi ll get
(N=450)
83.8% reported "No concerns or issues"15.6%
12.6%
11.7%
10.6%
10.0%
9.1%
8.7%
8.0%
0 25 50 75 100Unknown serious
side effects
No provider
recommendation
Effectiveness
Not enough studies
(human trials)
Mild side
effects
Perceived natural
immunity*
Had enough
vaccines*
Heart -related
issues
Weighted % (95% confidence interval)Probably will get/unsure
(N=157)
47.1% reported "No concerns or issues"53.2%
49.6%
48.6%
41.9%
37.7%
17.5%
13.2%
10.2%
0 25 50 75 100Unknown serious
side effects
Do not trust
gov. or pharma
Not enough studies
(human trials)
Effectiveness
Heart -related
issues
Had enough
vaccines*
Perceived natural
immunity*
Mild side
effects
Weighted % (95% confidence interval)Probably/definitely will NOT get
(N=275)
9.6% reported "No concerns or issues"
5050Key attitudes and experiences among adults 18 years and older, December 2023
National Immunization Survey -Adult COVID Module (NIS -ACM)
The December estimates are based on data collected November 26 through December 30.
CDC. COVID -19 Vaccination Coverage and Vaccine Confidence Among Adults. https://www.cdc.gov/vaccines/imz -managers/coverage/covidvaxview/interactive/adults.html
Accessed February 7, 2024COVID -19 Vaccination Key Attitudes and Experiences by Vaccination Status
Among Adults Age ≥18 Years, NIS -ACM, December 2023
19% of adults received a healthcare provider
vaccine recommendation; highest among
adults who were vaccinated or definitely plan
to get vaccinated.1931
26
1415
05101520253035
Healthcare provider recommended I get a COVID-19 vaccinePercent
Overall Vaccinated with 2023-24 COVID-19 vaccine
Definitely will get vaccinated Probably will get vaccinated or unsure
Probably or definitely will not get vaccinated
5151Key attitudes and experiences among adults 18 years and older, December 2023
National Immunization Survey -Adult COVID Module (NIS -ACM)
The December estimates are based on data collected November 26 through December 30.
CDC. COVID -19 Vaccination Coverage and Vaccine Confidence Among Adults. https://www.cdc.gov/vaccines/imz -managers/coverage/covidvaxview/interactive/adults.html
Accessed February 7, 2024COVID -19 Vaccination Key Attitudes and Experiences by Age Group
Among Adults Age ≥18 Years, NIS -ACM, December 2023
Healthcare provider recommendation was
highest among adults ages ≥65 years. 152227
051015202530
Healthcare provider recommended I get a COVID-19 vaccinePercent
18 - 49 years 50 - 64 years 65+ years
5252Intent to receive additional  COVID -19 vaccine dose among adults ≥18 years
of age who received a dose since September 14, 2023, Omnibus Surveys,
November 30, 2023 -January 16, 2024 (N=1,331)
*Labels for estimates <4% not shown. †NORC and Ipsos base urbanicity on different, but comparable measures. NORC uses Census tract -based RUCA (Rural -Urban -Commuting A rea) codes, whereas Ipsos uses Office of Management and
Budget's CBSA (Core Based Statistical Area) classification. §Includes plans purchased through employer, insurance companies, marketplaces, military insurance, Medicare, Medicaid, VA, IHS , and "other.“
Omnibus Surveys: 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
U.S. adults aged 18 years and older. CDC fields questions about vaccination status, intent, knowledge, attitudes, beliefs, an d behaviors on each survey for 2 waves each month, for a combined sample size of ~4,000
respondents. These slides present results from January (N=4,287). Data were weighted to represent the non -institutionalized U.S.  population and mitigate possible non -response bias. All responses are self -reported. 62.9 5.6 31.5
63.4
62.44.3
6.932.3
30.7
59.1
59.9
68.47.3
5.0
4.433.6
35.1
27.2
63.7
61.3
64.1
57.311.2
14.832.9
27.5
21.1
40.1
0 25 50 75 100Overall (N=1,331)
Female (N=629)Male (N=702)
Age 65+ (N=493)Age 50-64 (N=387)Age 18-49 (N=451)
Other, non -Hispanic* (N=114)Hispanic (N=129)Black, non -Hispanic (N=90)White, non -Hispanic* (N=998)
Weighted %66.3
60.9
60.86.6
7.330.0
32.5
31.8
57.0
62.7
65.3
62.911.1
6.4
4.4
5.331.9
30.9
30.3
31.9
58.8
60.0
65.1
65.14.7
6.5
6.2
4.936.5
33.5
28.7
30.0
63.1
53.25.6
9.831.2
37.0
0 25 50 75 100Rural (N=170)Suburban (N=654)Urban*†(N=507)
$75,000+ (N=837)$50,000- $74,999 (N=227)$25,000- $49,999 (N=180)Income $24,999 or less (N=87)
West (N=387)South (N=383)Midwest (N=340)Northeast (N=221)
Uninsured (N=33)Insured§(N=1,250)
Weighted %

Domain Equity Question:
Is the intervention equally acceptable across all
populations?

Among adults age ≥18 years responding to the NIS -ACM during Nov. 26 –  Dec. 30, 2023:
Vaccination coverage differed by race/ethnicity.
–Coverage was highest among White, non-Hispanic adults and lowest among American
Indian/Alaska Native and Native Hawaiian/Other Pacific Islander adults.
Vaccination coverage was higher in urban and suburban areas compared with rural
areas.
Adults with health insurance had significantly higher vaccination coverage than adults without insurance.
Vaccination coverage increased with increasing household income.Is the intervention equally acceptable across all populations?
NIS-ACM: National Immunization Survey -Adult COVID Module 54
5555Intent to receive additional  COVID -19 vaccine dose among adults ≥18
years of age who received a dose since September 14, 2023, Omnibus
Surveys, November 30, 2023 -January 16, 2024 (N=1,331)
*Labels for estimates <4% not shown. †NORC and Ipsos base urbanicity on different, but comparable measures. NORC uses Census tract -based RUCA (Rural -Urban -Commuting A rea) codes, whereas Ipsos uses Office of Management and Budget's CBSA (Core Based
Statistical Area) classification. §Includes plans purchased through employer, insurance companies, marketplaces, military insurance, Medicare, Medicaid, VA, IHS , and "other.“
Omnibus Surveys: 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 U.S. adults aged 18 years a nd
older. 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 ~4,000 respondents. These slides present results from January
(N=4,287). Data were weighted to represent the non -institutionalized U.S. population and mitigate possible non -response bias. Al l responses are self -reported. 62.9 5.6 31.5
63.4
62.44.3
6.932.3
30.7
59.1
59.9
68.47.3
5.0
4.433.6
35.1
27.2
63.7
61.3
64.1
57.311.2
14.832.9
27.5
21.1
40.1
0 25 50 75 100Overall (N=1,331)
Female (N=629)Male (N=702)
Age 65+ (N=493)Age 50-64 (N=387)Age 18-49 (N=451)
Other, non -Hispanic* (N=114)Hispanic (N=129)Black, non -Hispanic (N=90)White, non -Hispanic* (N=998)
Weighted %66.3
60.9
60.86.6
7.330.0
32.5
31.8
57.0
62.7
65.3
62.911.1
6.4
4.4
5.331.9
30.9
30.3
31.9
58.8
60.0
65.1
65.14.7
6.5
6.2
4.936.5
33.5
28.7
30.0
63.1
53.25.6
9.831.2
37.0
0 25 50 75 100Rural (N=170)Suburban (N=654)Urban*†(N=507)
$75,000+ (N=837)$50,000- $74,999 (N=227)$25,000- $49,999 (N=180)Income $24,999 or less (N=87)
West (N=387)South (N=383)Midwest (N=340)Northeast (N=221)
Uninsured (N=33)Insured§(N=1,250)
Weighted %

As of February 2024, v accination coverage with 2023 -2024 COVID -19 vaccine was
highest among older adults ages 65 –  74 years and 75+ years, compared to younger age
groups.
–Disparities in COVID -19 vaccine coverage are 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 they get a COVID- 19 vaccine.
–Adults ≥65 years were more likely to report a healthcare provider recommendation than
younger adults.
Among adults ≥65 years of age who had already received a 2023 -2024 Formula COVID -
19 vaccine dose, 68.4% reported they definitely will get an additional dose of 2023 -
2024 Formula COVID -19 vaccine if it is recommended for them.Summary
Acceptability
56
Acceptability
Would recommending an additional dose of 2023 -2024 Formula COVID -19
vaccine for older adults be acceptable to key stakeholders?
•Are there key stakeholders that would not accept the distribution of benefits
and harms?
•Are there key stakeholders that would not accept the undesirable effects in the short term for the desirable effects (benefits) in the future?
oNooProbably no oProbably yes oYesoVaries oDon’t know
Minority opinion  Majority opinion
EtR Domain:
Feasibility

59COVID -19 vaccines are now available on the commercial market.
–COVID -19 vaccines are covered by private and public insurance and available through
the Bridge Access Program and Vaccines for Children for those that are uninsured or
underinsured.
ACIP recommendation would be needed for insurance coverage of an additional dose of 2023- 2024 Formula COVID -19 vaccine.
–Insurance coverage generally required under either a “should” or “may” recommendation.Financial Barriers
60Additional dose recommendation would be for same formula (2023 -2024) of COVID -19
vaccine that is currently available.
–Existing COVID -19 vaccine administration infrastructure and product can be used.
–Age-based recommendation would not be overly burdensome to implement.
Additional dose recommendation in those ≥65 years would add complexity to COVID-
19 vaccine recommendations which have been getting simpler.
–Frequent changes to vaccine recommendations can lead to vaccine fatigue.
–Systems are already planning for next season, and adding more recommendations for this
year could add additional burden to an already fatigued system.
–Minimum interval of 4 months used for additional dose recommendations may confuse providers accustomed to 2 month interval from the fall dose.
–Providers would need to consider anticipated availability of updated vaccine next fall when considering providing vaccine doses during the summer months.Implementation and vaccine access
Domain Equity Question:
Is the intervention equally feasible to implement
across all populations?

Past reports of sites being unaware of additional dose recommendations or requiring
documentation to prove eligibility for additional vaccine dose.
–Wide communication of any change in recommendations and that self -attestation is
appropriate will be important to decrease barriers.
The Bridge Access Program was designed to remove patient barriers to COVID -19
vaccines, however disparities in vaccine uptake by insured status continue.
To the extent that existing disparities in vaccine uptake by characteristics such as race/ethnicity, urbanicity, and income are driven by differences in vaccine access, additional dose recommendations may further increase those disparities.
–Access issues may be increased during a time when there are fewer off -site vaccination
clinics, which are more common during fall vaccine roll -outs.
In the absence of an ACIP recommendation, additional doses might be an out- of-pocket
cost, therefore those able to pay for an additional dose may have access while others do not.Implementation equity considerations
62
COVID -19 vaccines currently on the commercial market and  an ACIP recommendation
(should or may) would be needed for insurance coverage of an additional dose.
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
and additional dose recommendations may further heighten those inequities, but lack of recommendation limits access to those able to pay for vaccine out -of-pocket.Summary
Feasibility
63
Feasibility
Is an additional dose of the 2023-2024 Formula COVID -19 vaccine feasible to
implement among older adults?
•Is the 2023- 2024 Formula COVID -19 vaccine program sustainable?
•Are there barriers that are likely to limit the feasibility of implementing the 2023 -
2024  Formula COVID -19 vaccine or require considerations when implementing it?
•Is access to the 2023- 2024 Formula COVID -19 vaccine an important concern?
oNooProbably no oProbably yes oYesoVaries oDon’t know
EtR Domain:
Resource Use

66Scenario analysis: probability of hospitalization1, societal
perspective
ICER ($/QALY)
Age
groupStrategy Base case ¼ base case ½ base case 2x base case 3x base case 4x base case
65+ yUpdated Covid- 19 vax, 1 dose $11,936 $93,904 $52,541 Cost saving Cost saving Cost saving
Updated Covid- 19 vax, 2 doses $255,122 $624,028 $433,533 $120,341 $64,599 $34,133
ICER=Incremental cost effectiveness ratio; QALY=Quality -adjusted life year
1 From Ko et al 2021. Adjusted risk of hospitalization by underlying condition: chronic obstructive pulmonary disease: 0.9, his tory of stroke: 0.9, coronary artery disease: 1.3,
asthma: 1.4, hypertension: 2.8, obesity: 2.9, diabetes: 3.2, chronic kidney disease: 4.0, severe obesity: 4.4.
Domain Equity Question:
Is the intervention a reasonable and efficient
allocation of resources across all populations?

An additional dose of COVID- 19 vaccine is most cost -effective in older adults in which
disease burden is highest compared to younger adults.
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.Is the intervention a reasonable and efficient allocation of
resources across all populations?
68
The cost effectiveness of an additional dose in older adults is highly sensitive to COVID-
19-associated hospitalization rates and anticipated rates in the coming months are
uncertain.
–COVID -19-associated hospitalization rates in older adults that are higher than those seen last
year would increase the cost effectiveness, however lower COVID -19 hospitalization rates
would decrease the cost effectiveness.
Estimates that approximate cost- effectiveness for those with high- risk conditions such
as underlying conditions or advanced age are more favorable.Resource Use
Summary
69
Resource Use
Is an additional dose of the 2023-2024 Formula COVID -19 vaccine in older
adults a reasonable and efficient allocation of resources?
•What is the cost- effectiveness of the 2023 -2024 Formula COVID -19 vaccine?
•How does the cost- effectiveness of the 2023 -2024 Formula COVID -19 vaccine change
in response to changes in context, assumptions, etc.?
oNooProbably no oProbably yes oYesoVaries oDon’t know
Summary and Work Group Interpretations
–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.
•Data presented today emphasized the importance of any dose of updated (2023 -
2024 Formula) 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.
•Within the ≥65 -year age group, risk increases with increasing age.
–Receipt of 2023- 2024 Formula COVID -19 vaccine provides protection against JN.1 and
other circulating variants, however vaccine effectiveness is expected to wane.
•In the past, we have seen greater durability in the protection against critical illness.Summary and Work Group Interpretations
72
–“May” recommendation would provide flexibility for older adults to obtain an
additional dose if they or their healthcare provider feel they would benefit.
•Most benefit would likely be in those with underlying medical conditions, advanced age, or circumstances that may increase risk (e.g., nursing home resident).
–Additional dose in adults ≥65 years may restore protection that has waned.
•Smaller, incremental benefit on top of the protection still being provided by the initial 2023 -2024 Formula COVID -19 vaccine dose.
–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. Summary and Work Group Interpretations
73
7474Considerations for an additional dose recommendation
Pros Cons
•“May” recommendation would provide
flexibility for those ≥65 years to get an additional dose if they or their healthcare provider feel they would benefit.•Smaller, incremental benefit compared to that from initial 2023 -2024 COVID -19
vaccine dose in the fall.
•Restore vaccine effectiveness that may have waned since the initial 2023 -2024
COVID -19 vaccine dose.•May decrease vaccine confidence in the benefits of a single dose of 2023 -2024
COVID -19 vaccine.
•Acknowledges that risk of severe illness due to COVID -19 continues throughout
the year for older adults, despite upticks during winter months.•Additional recommendations may increase vaccine fatigue, potentially reducing uptake of vaccine next fall.
75EtR Domain Question Work Group Judgments
Public Health
ProblemIs COVID -19 disease among persons ages 65 years and older of
public health importance?Yes
Benefits and HarmsHow substantial are the desirable anticipated effects? Moderate
How substantial are the undesirable anticipated effects? Small
Do the desirable effects outweigh the undesirable effects? Favors intervention
ValuesDo older adults feel that the desirable effects are large relative
to undesirable effects?Large
Is there important uncertainty about, or variability in, how older adults value the main outcomes?Probably important uncertainty
or variability
AcceptabilityWould recommending an additional dose of 2023 -2024 Formula
COVID -19 vaccine for older adults be acceptable to key
stakeholders?Probably yes
FeasibilityIs an additional dose of the 2023 -2024 Formula COVID -19
vaccine feasible to implement among older adults?Probably yes
Resource UseIs an additional dose of the 2023 -2024 Formula COVID -19
vaccine a reasonable and efficient allocation of resources?Probably yes
76Evidence to Recommendations Framework
Summary: Work Group Interpretations
Balance of
consequencesUndesirable
consequences
clearly
outweigh
desirable
consequences
in most
settingsUndesirable
consequences
probably
outweigh
desirable
consequences
in most
settingsThe balance
between
desirable and
undesirable
consequences
is closely
balanced or
uncertainDesirable
consequences
probably
outweigh
undesirable
consequences
in most
settingsDesirable
consequences
clearly
outweigh
undesirable
consequences
in most
settingsThere is
insufficient
evidence to
determine the
balance of
consequences
77Evidence to Recommendations Framework
Summary: Work Group Interpretations
Type of
recommendationWe do not recommend
the interventionWe recommend the
intervention for individuals
based on shared clinical
decision -makingWe recommend the
intervention
ACIP recommends that persons ≥65 years of age may receive an
additional dose of 2023 -2024 Formula COVID- 19 vaccineProposed ACIP Voting Language
78
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. Proposed Clinical Considerations
Note: For initial vaccination with Novavax COVID -19 Vaccine, the 2 -dose series should be completed before administration of the additional dose. 79
Acknowledgements
80Lakshmi Panagiotakopoulos
Monica Godfrey
Danielle Moulia
Katherine Fleming -Dutra
Ruth Link -Gelles
Sarah Meyer
Elisha Hall
Jennifer Kriss
Kayla Calhoun
Kevin Chatham- Stephens
Susan Goldstein
Mary Chamberland
JoEllen Wolicki
Lauren Roper
Karen Broder Evelyn Twentyman
Sierra Scarbrough
Natalie Thornburg
Jefferson Jones
Aron Hall
Dave Wentworth
COVID -NET
University of Michigan COVID -19 Vaccination Modeling
Team
Immunization Safety Office
Immunization Services Division
Coronavirus and other Respiratory Viruses Division
National Center for Immunization and Respiratory
Diseases
For more information, contact CDC
1-800- CDC- INFO (232 -4636)
TTY:  1 -888 -232-6348    www.cdc.gov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official
position of the Centers for Disease Control and Prevention.
Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation
use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.
Thank you

Summary: Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation  use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. Evidence to Recommendations Framework: Additional Dose of 2023-2024 Formula COVID -19 Vaccine in Older Adults  Megan Wallace, DrPH, MPH ACIP Meeting February 28, 2024…


07 COVID Panagiotakopoulos 508

Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation
use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.
Next Steps for the COVID- 19 Vaccine Program
Lakshmi Panagiotakopoulos, MD, MPH
ACIP MeetingFebruary 28, 2024
Can we improve the current COVID- 19
vaccine policy timeline?
mRNA updated (2023 –2024 Formula) vaccines were authorized or
approved on September 11, 2023
ACIP met September 12, 2023 to review the available evidence for
updated COVID -19 vaccines (monovalent, XBB.1.5 component)
ACIP recommended updated COVID -19 vaccines as authorized under EUA
or approved by BLA in persons aged ≥6 months:
–Moderna COVID -19 vaccine in persons ≥6 months
–Pfizer- BioNTech COVID -19 vaccine in persons ≥6 months
–Novavax COVID- 19 vaccine in persons ≥ 12 years*COVID- 19 Vaccine Policy Decision – Fall 2023
3ACIP: Advisory Committee on Immunization Practices  |  EUA: Emergency Use Authorization  |  BLA: Biologics License Application
*Novavax authorized for use on October 3, 2023
Timeline:  Fall 2023 COVID -19 Vaccine Recommendation
September 12
ACIP Vote and CDC
Recommendation
for the Updated
2023 -2024 COVID -
19 Vaccine
September 15
Updated
Interim Clinical
Considerations
on the Use of
COVID -19
Vaccines PostedSeptember 19
COCA Call on
Recommendations
for Influenza,
COVID -19, and RSV
Vaccines for Older
Adults
September 27
Immunization
scheduled
updatedOctober 3
Novavax
Updated 2023-
2024 COVID -
19 vaccine
authorized
October 10
MMWR on Use
of Updated
2023 –2024
COVID -19
Vaccines
ACIP: Advisory Committee on Immunization Practices  |  CDC: Centers for Disease Control and Prevention |  COCA: Clinician Outreach and Communication Activity |
MMWR: Morbidity and Mortality Weekly Report
https://www.cdc.gov/vaccines/covid -19/clinical- considerations/covid -19-vaccines -us.html  |  https://www.cdc.gov/mmwr/volumes/72/wr/mm7242e1.htm  4
COVID -19 related hospitalizations had already begun to increase before
the ACIP vote on use of the updated (2023 -2024) COVID -19 vaccine
Weekly COVID -19 new hospital admissions – National Healthcare Safety Network (NHSN), United States, June 2023 – January 2024
https://covid.cdc.gov/covid -data -tracker/#trends_weeklyhospitaladmissions_select_00
ACIP Vote and CDC
Recommendation
5
Uncertainty around recommendations made planning for state and local vaccine
programs challenging
Vaccine orders had to be placed prior to knowing groups for whom vaccine would be recommended
Stakeholder presentations, provider toolkits, and webpages all had to be updated after recommendation was made, limiting available window for communication of recommendation prior to the respiratory virus season
There were reports of issues with vaccine access, including among those at highest risk of severe illnessWhat happened after  the Fall updated (2023 -2024) COVID -
19 vaccine policy vote?
6
Less lead time for planning (e.g., staffing, scheduling, EHR prompts)
A new recommendation may occur during a surge in COVID -19 associated
hospitalizations and may not provide enough time for distribution, partner
engagement, preparation of healthcare providers and facilities, and uptake to mitigate the rise in disease
May limit ability to coordinate messaging surrounding the fall/winter respiratory virus season and promote importance of COVID -19 vaccination in communications
Likely limit ability to plan vaccination clinics with COVID -19, flu, and/or RSV vaccine in
settings such as long -term care facilities, communities, workplaces, and schools
EHR: Electronic health recordPotential impacts of continuing with a Fall vote for the
2024 -2025 COVID -19 vaccine
7
8Annual seasonal influenza vaccine timeline
Feb March April July May June Aug Sep Oct Nov Dec
WHO Vaccine
Composition
RecommendationsFDA VRBPAC
MeetingACIP votes on
proposed
recommendations
FDA issues sBLAsJan
Manufacturers distribute vaccine
Providers administer vaccine
WHO : World Health Organization | FDA: Food and Drug Administration | VRBPAC : Vaccines and Related Biologic Products Advisory Committee | ACIP : Advisory Committee on
Immunization Practices | CDC: Centers for Disease Control and Prevention | sBLAs : Supplemental Biologics License Applications CDC/ACIP
recommendations
published
Current Time Frame for Updated COVID -19 Vaccine Availability
Dec. Jan. Feb. Mar. Apr. May Jun. Jul. Aug. Sep. Oct. Nov. Dec.Year -round genetic and phenotypic characterization
WHO TAG -CO-VAC
Recommendation •Timing of TAG- CO-VAC recommendations and regulatory review for 2022 and 2023 shown
Vaccine manufacturing etc.
Vaccine distribution & administrationIdentify vaccine
candidates
Produce
antisera to
candidatesAnalyze neutralization of
recent virusesFDA
VRBPAC FDA license approval
Current timing for the vaccine strain composition is challenging for the manufacture and
distribution of vaccine early in the Fall
Slide for discussion purposes. Information is approximated and exact timelines for manufacturing are inferred.
WHO : World Health Organization | TAG -CO- VAC: Technical Advisory Group on Covid -19 Vaccine Composition  |  FDA : Food and Drug Administration | VRBPAC : Vaccines and
Related Biologic Products Advisory Committee | ACIP : Advisory Committee on Immunization PracticesACIP Rec.
9
Dec. Jan. Feb. Mar. Apr. May Jun. Jul. Aug. Sep. Oct. Nov. Dec.ACIP Rec. Revised Time Frame for 2024 -2025 COVID -19 Vaccine Availability
Year -round genetic and phenotypic characterization
Vaccine manufacturing etc.
Vaccine distribution & administrationIdentify vaccine
candidates
Produce
antisera to
candidatesAnalyze neutralization of
recent viruses
FDA
VRBPACFDA license approval
Proposed changes: WHO -TAG-CO-VAC mid -late April (exact date to be determined), FDA VRBPAC in May, ACIP in JuneWHO TAG -CO-VAC
Recommendation?
Slide for discussion purposes. Information is approximated and exact timelines for manufacturing are inferred.
WHO : World Health Organization | TAG -CO- VAC: Technical Advisory Group on Covid -19 Vaccine Composition  | FDA : Food and Drug Administration | VRBPAC : Vaccines and
Related Biologic Products Advisory Committee | ACIP : Advisory Committee on Immunization Practices
Vaccines and Related Biological Products Advisory Committee May 16, 2024 Meeting Announcement - 05/16/2024 | FDA10
ACIP meeting in June to review evidence for 2024 -2025 COVID -19 vaccine
recommendations, including:
–WHO and FDA antigen selections
–Manufacturer studies and immunogenicity data
–Cumulative effectiveness and safety data
–Epidemiology from current and prior years
–Uptake from current and prior years
–Cost effectiveness
ACIP vote on 2024 -2025 COVID -19 vaccine recommendations in June
2024 -2025 Formula will become available as regulatory actions are taken
by FDA and vaccines are distributed by manufacturersProposed COVID- 19 Vaccine Policy plan - 2024
ACIP : Advisory Committee on Immunization Practices  |  WHO : World Health Organization  |  FDA : Food and Drug Administration 11
Pros and Cons of a June COVID -19
vaccine policy decision
Enables early planning across entirety of healthcare delivery system
•National, state and local public health departments
•Large and small practices, other venues for vaccine delivery (e.g., pharmacies)
Allows time for clear communication of recommendations
Provides vaccine sites with earlier information on which to base ordering decisions
Vaccines potentially available immediately following FDA authorization or approval
Alignment with influenza vaccine recommendations
Decrease number of emergency ACIP meetingsPros of a June COVID- 19 vaccine policy decision
13FDA : Food and Drug Administration  | ACIP : Advisory Committee on Immunization Practices
–Epidemiology and strain changes
•Minor changes: unlikely to impact recommendation
•Major changes: may require subsequent emergency action
–Updated vaccine antigen changes do not require new human data
•Manufacturers provide pre- clinical immunogenicity for VRBPAC antigen selection
•Additional clinical trial data beyond that presented at VRBPAC may not be
available before ACIP votes (both for June and September)
•Reliance on large body of cumulative effectiveness and safety data
–Consistent temporal patterns of COVID -19 not yet established
•While this is true, we have four years worth of epidemiologic data to predict a peak in the winter 2024- 2025Potential cons of a June COVID -19 policy decision
VRBPAC : Vaccines and Related Biologic Products Advisory Committee  |  ACIP : Advisory Committee on Immunization Practices  14
We have more than four years worth of data on COVID -19 and three years worth of
data on COVID -19 vaccines
We have a well- established precedent from influenza vaccine recommendations
–Virus evolves rapidly and updates to vaccine antigens are needed
It is unlikely there will be more data between June and September to influence
updated COVID- 19 vaccine policy decision
Increased lead time will ease implementation challenges for vaccine providers
Increased lead time can also allow for clearer messaging in provider and patient educational materialsTakeaways
15
Important to separate policy question/decision from timing of decision
Work group members were in favor of moving decision to June, and
discussed many ways that this could ease implementation challenges,
including clearer communication of vaccine policy and increase lead
time for clinicians
Work group members emphasized that communication surrounding a
recommendation prior to updated vaccine availability, as done routinely
for influenza vaccine, will be importantWork Group Interpretation
16
Megan Wallace
Mary Chamberland
Kevin Chatham -Stephens
Matthew Daley
Katherine Fleming -Dutra
Monica Godfrey
Susan Goldstein
Lisa Grohskopf
Aron Hall
Elisha Hall
Sarah MeyerDanielle Moulia
Evelyn Twentyman
David Wentworth
JoEllen Wolicki
ACIP COVID -19 Work Group
Immunization Services Division
Immunization Safety Office
Coronavirus and Other Respiratory
Viruses Division
National Center for Immunization and Respiratory Diseases Acknowledgements
17
For more information, contact CDC
1-800- CDC- INFO (232 -4636)
TTY:  1 -888 -232-6348    www.cdc.gov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official
position of the Centers for Disease Control and Prevention.
Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation
use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.

Summary: Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation  use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. Next Steps for the COVID- 19 Vaccine Program Lakshmi Panagiotakopoulos, MD, MPH ACIP MeetingFebruary 28, 2024 Can we improve the current COVID- 19  vaccine policy…


01 Chikungunya chen 508

CHIKUNGUNYA VACCINES
Wilbur Chen, MD, MS
Chair, ACIP Chikungunya Vaccines Work GroupACIP Meeting
February 28, 2024
Background
Chikungunya vaccine (manufactured by Valneva) was licensed in the
United States in November 2023
No other chikungunya vaccine licensed globally
No existing ACIP chikungunya vaccine recommendations
Chikungunya Vaccines Work Group is developing policy options for ACIP’s consideration for use of chikungunya vaccine among U.S. persons at risk of
chikungunya, including travelers, laboratory workers, and residents of U.S.
territories and states with risk of transmission
Recap of previous Work Group presentations to ACIP (1)
October 2022
–Overview of chikungunya virus disease and vaccines
–Immunogenicity and safety of Valneva’s chikungunya vaccine
February 2023
–Global epidemiology of chikungunya
–Chikungunya among U.S. travelers
–Persistent arthralgia following chikungunya
June 2023
–Value of a vaccine to U.S. travelers
–Chikungunya virus infection among laboratory workers
–Observations on a large chikungunya outbreak in Paraguay
Recap of previous Work Group presentations to ACIP (2)
October 2023
–Evidence to Recommendations ( EtR) and proposed policy options for
chikungunya vaccine use among U.S. adult travelers
–EtR and proposed policy options for chikungunya vaccine use among
U.S. laboratory workers
Overview of today’s session
Update on chikungunya vaccine licensure
Review of proposed policy options for chikungunya vaccine use among
U.S. adult travelers *
Review of proposed policy options for chikungunya vaccine use among
U.S. laboratory workers *
Proposed clinical guidance for vaccine use among pregnant and
breastfeeding persons
*For vote today
ACIP Ex Officio ( cont ) Invited Consultants ( cont )
Wilbur Chen, Univ Maryland Lesley Dupuy, NIH Beth Bell, Univ Washington
Matthew Daley, Kaiser Permanente Carina Blackmore, Florida Dept Health
ACIP Liaisons Alan Lam, DoD
CDC Leads Elizabeth Barnett, ISTM Margaret Ryan, DoD
Susan Hills, DVBD (Lead) James Campbell, AAP Steven Schofield, CATMAT
Nicole Lindsey, DVBD (Deputy Lead) Mary Pat Friedlander, AAFP David Shlim, Jackson Hole Travel & Trop Med
Saroj Rai, AIM Nestor Sosa, Uni New Mexico Hospital
Ex Officio Sanet Torres, San Jorge Children & Women's Hospital
Robin Levis, FDA Invited Consultants Kirsten Vannice, Bill & Melinda Gates Foundation
Sixun Yang, FDA Alan Barrett, Univ Texas Galveston Mary Wilson, Univ California San FranciscoChikungunya Vaccines Work Group members
DVBD DGMQ ISD
Erin Staples Kevin McLaughlin Elisabeth Velazque z
Sarah Guagliardo
Ann Powers DHQP GRADE/ETR consultants
Laura Adams Michael McNeil Doug Campos -Outcalt
Joshua Wong Rebecca Morgan
GID
NCEZID Rebecca Casey ACIP Secretariat
Rita Helfand Jessica MacNeil, NCIRD
Leslie Lee, NCIRDChikungunya Vaccines Work Group CDC participants

Summary: CHIKUNGUNYA VACCINES Wilbur Chen, MD, MS Chair, ACIP Chikungunya Vaccines Work GroupACIP Meeting February 28, 2024 Background Chikungunya vaccine (manufactured by Valneva) was licensed in the  United States in November 2023 No other chikungunya vaccine licensed globally No existing ACIP chikungunya vaccine recommendations Chikungunya Vaccines Work Group is developing policy options for ACIP’s consideration for use of chikungunya vaccine among U.S. persons at risk of  chikungunya, including…


02 Chikungunya hills 508

National Center for Emerging and Zoonotic Infectious Diseases
UPDATE ON LICENSURE OF LIVE
ATTENUATED CHIKUNGUNYA VACCINE
Susan Hills, MBBS, MTH
CDC Lead , Chikungunya Vaccines Work Group
Arboviral Diseases Branch
Division of Vector -Borne Diseases
Fort Collins, Colorado
   ACIP meeting, February 28, 2024
Key points from FDA licensure and package insert
Vaccine approved on November 9, 2023 and named IXCHIQ
Indicated for individuals at increased risk of exposure to chikungunya virus
Single dose primary schedule and for use in individuals aged ≥18 years

Contraindications
Immunocompromised individuals
Individuals with a history of a severe allergic reaction (e.g.,
anaphylaxis) to any component of IXCHIQ
2
Warnings and precautions in package insert
Vaccine may cause severe or prolonged chikungunya -like adverse
reactions
Vaccine viremia occurs in the first week following vaccination and
no data on risk of vertical transmission to fetus or neonate
Licensure through accelerated approval pathway
Tradition approval would have been challenging and clinical development
would likely have been delayed
–Chikungunya outbreaks unpredictable and duration can be relatively short
–No established immunologic correlate of protection
Accelerated approval pathway endorsed at FDA VRBAC* meeting, 2019
–FDA can grant for products for serious conditions that fill unmet medical need
–Effectiveness demonstrated by controlled clinical trials showing vaccine has effect
on surrogate endpoint reasonably likely to predict clinical benefit
–Marker of protection for chikungunya vaccine based on neutralizing antibody titer estimated from validated non -human primate model
–Post-licensure requirement for controlled trials to confirm the clinical benefit
*Vaccines and Related Biological Products Advisory Committee
Required post -marketing studies
Vaccine effectiveness case -control study in persons aged ≥12 years,
Brazil
–Plan to initiate by March 2026, complete by March 2028
Pragmatic randomized controlled trial for effectiveness and safety in
adults in endemic area
–Plan to initiate by Oct 2025, complete by Jul 2029

Summary: National Center for Emerging and Zoonotic Infectious Diseases UPDATE ON LICENSURE OF LIVE  ATTENUATED CHIKUNGUNYA VACCINE Susan Hills, MBBS, MTH CDC Lead , Chikungunya Vaccines Work Group Arboviral Diseases Branch Division of Vector -Borne Diseases Fort Collins, Colorado    ACIP meeting, February 28, 2024 Key points from FDA licensure and package insert Vaccine approved on November 9, 2023 and named IXCHIQ Indicated for individuals at increased risk of exposure to chikungunya virus   Single…


03 Chikungunya hills 508

National Center for Emerging and Zoonotic Infectious Diseases
PROPOSED POLICY OPTIONS FOR
CHIKUNGUNYA VACCINE USE AMONG
U.S. ADULT TRAVELERS
Susan Hills, MBBS, MTH
CDC Lead , Chikungunya Vaccines Work Group
Arboviral Diseases Branch
Division of Vector -Borne Diseases
Fort Collins, Colorado
   ACIP meeting, February 28, 2024
Chikungunya virus and transmission
Alphavirus
Key vectors are Aedes aegypti
and Aedes albopictus mosquitoes
Mainly feed in daytime with peak
activity early morning and late
afternoon

Other uncommon transmission modes
Intrauterine Intrapartum
Bloodborne Laboratory
exposure

Distribution and disease burden in endemic areas
Typically tropical and
subtropical regions
Periodically causes large outbreaks
–Often high attack rates
Virus transmission usually
highest during wet season
Large numbers of cases reported annuallyCountries and territories with current or past transmission
of chikungunya virus

Clinical features of acute chikungunya virus infection
Febrile illness with typically severe
arthralgia, can be debilitating
Joint symptoms involve multiple joints, most commonly hands and
feet
Other symptoms include
headache, rash, myalgia, anorexia
No anti -viral treatment available
Image above from : https://www.paho.org/en/topics/chikungunya
Complications of chikungunya
Rare serious complications (e.g.,
myocarditis, hepatitis, acute renal disease,
neurologic illness)
Deaths rare and reported mostly in
–Older adults, particularly those with
comorbidities
–Young infants infected perinatally or by mosquito bites
Images from : https://www.paho.org/en/topics/chikungunya
Chronic arthralgia following chikungunya
Acute symptoms usually resolve in 7 –10 days
Some patients have continuation or relapse of symptoms
Studies reported variable proportions of
patients with persistent symptoms and likely
varies with
–Severity of acute illness
–Age
–Preexisting joint problems
Ongoing arthralgia of variable severity possibly
present in up to ~50% at 3 months and up to
~30% at 12 months
Chikungunya among U.S. travelers
Approximately 100 –200 reported cases
annually
Infection most commonly acquired in
locations in Asia and Americas
Greatest risk factor for travelers is traveling to area with outbreak
Example of higher risk during outbreak: Risk for travelers
to Paraguay in 2023
<1%
Percentage of all U.S. persons
traveling to areas with
chikungunya risk visiting Paraguay 25%*
Percentage of all reported U.S. traveler
chikungunya cases who indicated they
had traveled to Paraguay
*20 of 80 travelers with destination data, preliminary ArboNET  data, 2023
Chikungunya vaccine
Live attenuated vaccine
Single dose schedule
Administered intramuscularly
Licensure based on data from
–~620 subjects for immunogenicity
–~3,500 subjects for safety (including ~3,100 in pivotal clinical trial)
Short - and long -term protection ( seroresponse  rates)
Short -term protection (28 days after vaccination)
–98% (611 of 622) combined seroresponse  rate from two studies
Long-term protection (12 months after vaccination)
–99% (356 of 360) seroreponse rate from one study
Work Group summary
–Although data are limited, vaccine highly immunogenic
Vaccine safety (1)
Pivotal Phase 3 clinical trial included 3,082 adults in vaccine arm and
1,033 in placebo arm
Solicited local reactions  within 10 days after vaccination
–15% in vaccinees vs 11% in placebo recipients
Solicited systemic adverse events  (AE) within 10 days after vaccination
–50% in vaccinees vs 27% in placebo recipients
–Most common were headache, fatigue and myalgia in ~25% –30% of vaccinees
Any related severe sy stemic AEs *
–1.9% in vaccinees vs 0.1% in placebo recipients
–Commonest were fever (1.3%), arthralgia (0.3%), myalgia (0.3%)
*Prevented daily activity or required medical attention or fever ≥39°C (102.1° F)
Vaccine safety (2)
Serious adverse events  within 6 months of vaccination
–1.5% in vaccinees vs 0.8% of placebo recipients
–Two events in vaccinated subjects considered vaccine -related
Arthr algia/arthritis
–Any arthralgia within 10 days in 17% vaccinees vs 5% placebo recipients
–Severe arthralgia, persistent arthralgia, arthritis, and new onset or worsening
osteoarthritis not reported in significantly higher percentage of vaccinees vs placebo recipients
Chikungunya- like adverse reactions: Background
Safety outcome of interest has been chikungunya -like illness after vaccination
Work Group had reviewed data on “adverse events of special interest” defined
by manufacturer
FDA-requested reanalysis based on revised case definition that was less
restrictive in terms of timing of onset of events, clustering of symptoms, and
duration of events
–Revised FDA definition was fever* and ≥1 of arthralgia or arthritis, myalgia,
headache, back pain, rash, lymphadenopathy, or certain neurological, cardiac or
ocular symptoms that occurred within 30 days after vaccination
* Fever ≥100.4 °F
Chikungunya- like adverse reactions: Results per reanalysis
Chikungunya -like adverse reactions
–11.7% (361 of 3,082) vaccine recipients and 0.6% (6 of 1,033) placebo
recipients
–Most symptoms mild or moderate
Severe reactions that prevented daily activity or required medical
intervention, or fever ≥102.1 °F (39° C)
–1.6% (n=48) vaccine recipients vs 0% of placebo recipients
Prolonged reactions with duration ≥30 days
–0.5% (n=14) vaccine recipients vs 0% of placebo recipients
Chikungunya- like adverse reactions:
Work Groups conclusions
Already considered reactogenic nature of vaccine
Looked closely at similar events when conducting GRADE analysis
Noted some other reactogenic vaccines have similar rates of adverse events
In Evidence to Recommendations framework when considering if desirable
effects outweighed undesirable effects of vaccination had noted risk -benefit
assessment
–Will vary substantially depending on chikungunya virus transmission intensity
and other factors
–Was likely favorable if used in line with our proposed recommendations
No change in Work Group assessment
Vaccine safety: Work Group summary
Reactogenic vaccine
Will be important to continue to monitor vaccine safety post -
licensure
Summary of Work Group considerations
Disease that can result in severe arthralgia during the acute illness,
rare serious complications, and sometimes long -term arthralgia
Highest risk for severe outcomes is among older adults, particularly those with comorbidities, and neonates and young infants
Moderate disease burden among US travelers with 100- 200 cases
reported annually
Substantially higher risk for infection if travel during an outbreak
Immunogenic but reactogenic vaccine
Draft recommendations for
ACIP’s consideration
Draft recommendations
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
Providing clarity on chikungunya outbreaks
For the purposes of the recommendation, an outbreak
will be defined as occurring when CDC posts information on an outbreak on CDC website
Shared clinical decision- making recommendation for
persons aged >65 years or traveling for a longer duration
More uncertainty in risk -benefit assessment in these cases
Likely to be circumstances where some individuals might reasonably
choose vaccination or some providers might wish to recommend it
Appropriate to hold conversation between healthcare provider and patient about the risks and benefits including
–likelihood of exposure based on factors including activities, time of year,
duration of travel
–disease and potential severity
–vaccine efficacy
–possibility of vaccine -associated adverse events
Takes into account traveler’s personal perceptions and tolerance of risk
Persons >65 years, particularly those with underlying
medical conditions
Key risk factors for severe disease include older age and underlying
medical conditions (e.g., diabetes, cardiac disease, hypertension)
Key risk factors for chronic arthralgia are older age and pre -existing joint
problems
1. To ra le s  M, e t al.  MMWR Morb  Mortal Wkly  R ep 2023
Vaccine not
available for
children Risk for higher morbidity and
mortality in older persons
supported by data from recent
outbreak in Paraguay1
Travel for cumulative period of ≥6 months
Key risk factor for chikungunya virus infection is intensity of
transmission
–If equivalent transmission, cumulative duration of exposure important
Transmission patterns can be unpredictable over longer term and likely  some seasonal variation in mosquito activity impacting risk
Expatriates in location with risk might not have access to vaccine if risk increased or outbreak began
Providing clarity on evidence of chikungunya virus
transmission among humans within the last 5 years
Rationale: 5 -year time frame provides interval that allows reasonable
confidence there is transmission or insufficient transmission to be concern
for travelers
Tool: Map that shows countries
with chikungunya virus
transmission among humans
reported during last 5 years,
posted on CDC website
Mock -up map to demonstrate transmission of chikungunya virus
among humans during last 5 years

Providing clarity on moderate exposure
Travelers who might have at least 2 weeks (cumulative) of exposure to
mosquitoes in indoor and/or outdoor settings
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)
65
Work Group deliberations when developing
recommendations
Aim to balance desirable and undesirable effects of vaccination
–“Recommended”: for travelers with highest risk
–“May be considered”: some individuals might reasonably choose
vaccination and some providers might wish to recommend it
Draft recommendations
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
*Moderate exposure could include travelers who might have at least 2 weeks (cumulative) of exposure to mosquitoes
in indoor and/or outdoor settings

Summary: National Center for Emerging and Zoonotic Infectious Diseases PROPOSED POLICY OPTIONS FOR  CHIKUNGUNYA VACCINE USE AMONG  U.S. ADULT TRAVELERS Susan Hills, MBBS, MTH CDC Lead , Chikungunya Vaccines Work Group Arboviral Diseases Branch Division of Vector -Borne Diseases Fort Collins, Colorado    ACIP meeting, February 28, 2024 Chikungunya virus and transmission Alphavirus  Key vectors are Aedes aegypti  and Aedes albopictus mosquitoes Mainly feed in daytime with peak  activity early morning…


04 Chikungunya hills 508

National Center for Emerging and Zoonotic Infectious Diseases
PROPOSED POLICY OPTIONS FOR
CHIKUNGUNYA VACCINE USE AMONG
U.S. LABORATORY WORKERS
Susan Hills, MBBS, MTH
CDC Lead , Chikungunya Vaccines Work Group
Arboviral Diseases Branch
Division of Vector -Borne Diseases
Fort Collins, Colorado
   ACIP meeting, February 28, 2024
Chikungunya virus infections among laboratory workers
At least 44 infections identified among laboratory workers worldwide over
~ 50 years1–3
–43 cases overt disease, 1 asymptomatic infection, no deaths
4 disease cases in U.S. laboratorians since chikungunya became notifiable disease in 2015
–Similar symptoms as with infection acquired via mosquito -borne route
–One case hospitalized for observation, no deaths
Identified cases underestimate all infections as no formal laboratory surveillance system
1.The Subcommittee on Arbovirus Laboratory Safety of the American Committee on Arthropod -Borne Viruses. Am J Trop Med Hyg 1980;
2.Rusnak JM, et al. J Occup Environ Med 2004; 3. US national arboviral disease surveillance system, 2015 –2022
Routes of laboratory transmission
Aerosol
Percutaneous
–Needlestick while working with and
injecting mice
–Forceps prick while dissecting mosquitoes infected with chikungunya virus
Mucosal (possible)

Factors for consideration
Vaccination required for only limited number of staff who might be
exposed to live chikungunya virus
–Vaccination not necessary for workers handling routine clinical samples
–Recommendations only for laboratorians undertaking research or very
specific diagnostic work using live virus (e.g., plaque reduction
neutralization tests)
Work group summary
–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
Draft recommendation
Chikungunya vaccination is recommended for laboratory
workers with potential for exposure to chikungunya virus.
Information accompanying recommendations
Local biosafety committee should undertake risk assessment
of potential for chikungunya virus exposure considering
–Type of work to be performed
–Biosafety level at which work is being conducted
Vaccination not necessary for workers handling routine clinical samples
Draft recommendation
Chikungunya vaccination is recommended for laboratory
workers with potential for exposure to chikungunya virus.

Summary: National Center for Emerging and Zoonotic Infectious Diseases PROPOSED POLICY OPTIONS FOR  CHIKUNGUNYA VACCINE USE AMONG  U.S. LABORATORY WORKERS Susan Hills, MBBS, MTH CDC Lead , Chikungunya Vaccines Work Group Arboviral Diseases Branch Division of Vector -Borne Diseases Fort Collins, Colorado    ACIP meeting, February 28, 2024 Chikungunya virus infections among laboratory workers At least 44 infections identified among laboratory workers worldwide over  ~ 50 years1–3  –43 cases overt…


05 Chikungunya hills 508

National Center for Emerging and Zoonotic Infectious Diseases
CLINICAL GUIDANCE FOR USE OF LIVE ATTENUATED
CHIKUNGUNYA VACCINE AMONG PREGNANT AND
BREASTFEEDING INDIVIDUALS
Susan Hills, MBBS, MTH
CDC Lead , Chikungunya Vaccines Work Group
Arboviral Diseases Branch
Division of Vector -Borne Diseases
Fort Collins, Colorado
   ACIP meeting, February 28, 2024
Clinical guidance for use of live attenuated
chikungunya vaccine in pregnant individuals
Presentation of chikungunya among pregnant persons
Clinical disease similar to  non-pregnant persons
Outcomes of chikungunya virus infection during pregnancy
Adverse outcomes such as fetal loss, stillbirth, or preterm birth
documented but rare
–Mouse studies and examination of placentas from infected women suggest
placenta is refractory to chikungunya virus infection1,2
Infection commonly  results in adverse neonatal outcomes if pregnant
individual infected around time of delivery
–In these cases, intrapartum transmission occurs in ~30% –50% cases3–6
–Mechanism considered to be transplacental transmission with hypothesis that maternal blood enters fetal circulation by placental barrier breaches
from uterine contractions during labor
1. Fritel   X et al, Emerg  Infect Dis 2010; 2. Couderc T et al, PLoS Pathog 2008; 3. Gerardin P et al, PLoS Medicine 2008; 4. Ramful D et al, Ped Infect Dis J 2007; 5.
Torres JR et al, Int J Infect Dis 2016; 6. Senanayake MP et al, Ceylon Med J 2009.
Disease in neonates infected via intrapartum transmission
Severe and sometime fatal illness
–In one prospective study 53% (10 of 19 neonates) had severe disease1
Presentations include encephalopathy, sepsis -like illness, cardiac,
dermatologic, and hemorrhagic manifestations
Neurocognitive outcomes often poor, particularly if initial clinical
presentation with encephalopathy
Bin S et al, Clin Case Rep 2023
 Jebain  J et al, ID Cases 2020
 Villamil -Gomez W et al, J Trop Ped 2015
1. Gerardin  P et al, PLoS  Medicine 2008
Chikungunya and young infants
Young infants infected via
mosquito -borne transmission
also at risk for severe disease, particularly during the first few months of life
Clinical presentations similar to those with neonatal infections
Valamparampil  JJ et al, Ind J Ped 2009
Gupta D et al, Ind J Ped 2015
Vaccination during pregnancy: Immunogenicity
No data available on immunologic response to chikungunya vaccine
administered to pregnant individual
General principles and experience with other vaccines
–Transplacental transfer of antibodies after maternal immunization demonstrated
to confer protection with most vaccines
–Examples of benefits include decreased rates of hospitalization in infants born to
vaccinated women (e.g., influenza, COVID -19, RSV vaccines) and decreased risk
for preterm birth (e.g., COVID -19 vaccine)
Vaccination during pregnancy: Safety
Data are insufficient to determine whether any safety risks from vaccination
during pregnancy
–Pregnancy was an exclusion criteria in clinical trials
–Only two pregnant persons inadvertently vaccinated during pregnancy
Two pregnant persons vaccinated during 1st trimester
–36-year -old: spontaneous abortion 59 days after vaccination at gestational age
~10– 14 weeks
–23-year -old: anembryonic pregnancy noted at 53 days, spontaneous abortion at 55
days after vaccination at ~8 weeks gestation
General notes on cases
–Anembryonic pregnancies generally result from chromosomal problem at conception
–Estimated 20%– 25% of all pregnancies lead to pregnancy loss, with highest rates in
1st trimester and increasing rates with increasing maternal age
Key language related to pregnancy in package insert1
Noted under “Warnings and Precautions”
–Vertical transmission of wild-type  chikungunya virus from pregnant individuals with
viremia at delivery is common and can cause potentially fatal chikungunya virus
disease in neonates. Vaccine  viremia occurs in the first week following administration
of chikungunya vaccine….it is not known if the vaccine virus can be vertically transmitted and cause fetal or neonatal adverse reactions
Noted under “Use in Specific Populations”
–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....If neonates are born within 14 days of their mother receiving chikungunya vaccine, closely monitor them after birth for potential disease due to vaccine virus
1. FDA. Package Insert –  IXCHIQ. Available at: https://www.fda.gov/vaccines -blood -biologics/ixchiq
Viremia after vaccination
In Phase 1 clinical trial
–Viremia after vaccination assessed by quantitative reverse transcription-
polymerase chain reaction ( qRT-PCR)
–Plasma tested on days 3, 7, and 14 after vaccination
Among 30 subjects vaccinated with vaccine dose with equivalent amount
of attenuated chikungunya virus as in licensed vaccine, viremia detected in
–90% on day 3
–17% on day 7
–0% on day 14
For many live vaccines, pregnancy is contraindication
–Theoretical risk to fetus from maternal viremia and viral transmission to fetus
–MMR and varicella vaccines contraindicated during pregnancy, although no
cases of congenital rubella or varicella syndrome or abnormalities attributable to fetal infection observed among infants born to women inadvertently vaccinated during pregnancy
For some live vaccines, pregnancy is precaution
–Vaccines can be used after considering the risks of disease and risks and benefits of vaccination
–Yellow fever, dengue vaccines
Kroger A et al. General Best Practice Guidance for Immunization (https://www.cdc.gov/vaccines/hcp/acip -recs/general -recs/index.h tml) Live, attenuated vaccines and pregnancy:
ACIP General Best Practice Guidelines for Immunization
Groups for whom clinical guidance will be relevant
Travelers and laboratory workers
Persons in U.S. territories and states with risk of chikungunya virus
transmission
Objectives of vaccinating pregnant individuals
Protect pregnant person from chikungunya virus infection
Avoid maternal infection around time of delivery to prevent
intrapartum virus transmission and severe disease in newborn
Transplacental transfer of antibodies might also protect young infant from mosquito -borne transmission and severe disease
Proposed clinical guidance for use of chikungunya
vaccine in pregnant individuals (1)
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).
Proposed clinical guidance for use of chikungunya
vaccine in pregnant individuals (2)
Pregnancy is a precaution for vaccination with the 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 health care 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.
Proposed clinical guidance for use of chikungunya
vaccine in pregnant individuals (3)
If pregnant persons choose to be vaccinated, out of caution vaccination should
generally be avoided during the 1st trimester (until 14 weeks gestation)  and after the
36th week of gestation.
oAvoiding vaccination during the 1st trimester is preferred for two reasons. Firstly,
pregnancy loss has been reported in two individuals vaccinated during the 1st
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
1st trimester.
oAvoidance 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.
Proposed clinical guidance for use of chikungunya
vaccine in pregnant individuals (4)
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 weeks after 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.
Guidance that maximizes benefits of vaccination while
minimizing risks associated with vaccination during pregnancy
1. Avoid risk if possible
2. In general, defer vaccination until after delivery
3. If exposure risk high, consider vaccination given risk for severe adverse
outcomes of infection particularly if intrapartum transmission occurs
4. If consider vaccination, where possible avoid 1st trimester and after 36th
week of gestation
Clinical guidance for use of live attenuated
chikungunya vaccine in breastfeeding individuals
Chikungunya and breastfeeding
Chikunguny a viral ribonucleic acid (RNA) detected in breast milk on
very rare occasions1,2
–No studies have reported detection of replicating virus
Case report describing mother with chikungunya and chikungunya
virus RNA detected in her breast milk was breastfeeding her 3 -
month -old infant1
–No symptoms or laboratory evidence of infection in infant
1. Campos GS et al, Pediatr  Infect Dis J 2017; 2. De Paula Souza et al, Transl  Res 2023.
Chikungunya vaccine and breastfeeding
No human data on whether chikungunya vaccine virus or antibodies are
present in breast milk after vaccination
Neonates and other infants aged <1 year are at risk for severe disease if infected with wild -type chikungunya virus
–Vaccine virus is attenuated, but outcome if chikungunya vaccine virus was
transmitted by breastfeeding unknown
Key language related to lactation in package insert1
Breastfeeding is neither contraindication nor precaution for vaccination
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 chikungunya
Vaccine viremia occurs after vaccination…the potential for transmission of vaccine virus from mother to infant through breastmilk is unknown
1. FDA. Package Insert –  IXCHIQ. Available at: https://www.fda.gov/vaccines -blood -biologics/ixchiq
Live attenuated vaccines and breastfeeding:
ACIP General Best Practice Guidelines for Immunization
Although live viruses in vaccines can replicate in mother, majority of live
viruses in vaccines have been shown not to be excreted in milk
–Varicella vaccine virus has not been detected in human milk
–Rubella vaccine virus has been detected in human milk, but virus usually does
not infect infant, and if infection occurs, the attenuated virus is well tolerated
Live vaccines considered to be safe for administration to breastfeeding
individuals with two exceptions:
–Yellow fever vaccine: three breastfed infants developed encephalitis after mother
vaccinated
–Smallpox vaccine (ACAM2000): theoretical risk for contact transmission from mother to infant
Kroger A et al. General Best Practice Guidance for Immunization (https://www.cdc.gov/vaccines/hcp/acip -recs/general -recs/index.h tml)
ACIP breastfeeding guidance for other live vaccines
MMR: Not a precaution or contraindication
Varicella: Not a precaution or contraindication
Yellow fever: Precaution
Smallpox (ACAM2000): Contraindication
Groups for whom clinical guidance will be relevant
Travelers and laboratory workers
Persons in U.S. territories and states with risk of chikungunya virus
transmission
Objectives of vaccinating breastfeeding individuals
Protect breastfeeding individual
Added benefit might be reduction in risk for infant through transfer
of protective antibodies in breast milk
Proposed clinical guidance 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.
Acknowledgements
Dana Meaney -Delman
Nicole Lindsey
Erin Staples
ACOG and AAP members for their review of draft clinical guidance
Chikungunya Vaccines Work Group members

Summary: National Center for Emerging and Zoonotic Infectious Diseases CLINICAL GUIDANCE FOR USE OF LIVE ATTENUATED  CHIKUNGUNYA VACCINE AMONG PREGNANT AND  BREASTFEEDING INDIVIDUALS Susan Hills, MBBS, MTH CDC Lead , Chikungunya Vaccines Work Group Arboviral Diseases Branch Division of Vector -Borne Diseases Fort Collins, Colorado    ACIP meeting, February 28, 2024 Clinical guidance for use of live attenuated  chikungunya vaccine in pregnant individuals Presentation of chikungunya among pregnant…