Mpox 06 Carter 508

Mpox Vaccine Implementation and Interim Clinical
Considerations
Rosalind Carter, PhD
Vaccine Task Force
2022 Multinational Mpox Response
Centers for Disease Control and Prevention
Advisory Committee on Immunization Practices
February 22, 2023
www.cdc.gov/mpo x

   Interim Clinical Considerations (ICC) is a living
document
• Continued emphasis on vaccination : Mpox vaccination should continue to be
offered to people with the highest potential for exposure to mpox .
• Updated guidance : People with HIV infection or other causes of
immunosuppression who have had recent or anticipate potential mpox
exposure should be vaccinated against mpox.
• New emphasis on inclusion of adolescents : The principal risk group was
reworded as “Gay, bisexual, and other men who have sex with men, and transgender or nonbinary people (including adolescents who fall into any of the aforementioned categories) … “

       Available Vaccines for Mpox
• JYNNEOS
• Primary vaccine for mpox outbreak in U.S.
• Licensed in the U.S. for subcutaneous administration in individuals 18
years or older
• FDA Expanded Use Authorization (EUA) in Aug 2022
• Intradermal administration for individuals 18+
• Subcutaneous administration for individuals <18 at high risk for mpox infection
• ACAM2000
• Available, but not used during current outbreak
• Higher risk of serious adverse events, including myocarditis

    U.S. National Mpox Vaccine Strategy
• U.S. National Mpox Vaccine
Strategy – June 2022
 Vaccinate and protect people at risk
 Prioritize vaccine allocations based
on reported case numbers
 Provide guidance to health officials
for planning and response
• Multiple federal agencies
coordinating to implement mpox vaccine strategy
 ASPR (SNS, BARDA), CDC, FDA

 Strategy
e

Vaccination  Prior   to Exposure  Vaccination before  exposure  to  mpox Vaccination Strategies
Post-Exposure Prophylaxis   (PEP) Vaccination   after known or presumed  exposure
to  mpox

 Post-Exposure Prophylaxis
• People who are known contacts to a person with mpox, and identified by public
health authorities as a “contact” (for example, from case investigation, contact tracing, or risk exposure assessment); or
• People who are aware that a recent (within the past 14 days) sex partner was diagnosed with mpox; or
• Gay, bisexual, other men who have sex with men, and transgender or nonbinary people (includes adolescents) who have had any of the following within the past 14 days:
 sex with multiple partners (or group sex);
 sex at a commercial sex venue; or
 sex in association with an event, venue, or defined geographic area where mpox
transmission is occurring

                 Vaccination prior to exposure to mpox virus
Offered to people with highest potential for exposure or who anticipate potential exposure to mpox , including:
• Gay, bisexual, and other men who have sex with men, and transgender or nonbinary people (including adolescents)
who, within the past 6 months, have had:
 A new diagnosis of one or more sexually transmitted diseases (e.g., chlamydia, gonorrhea, syphilis); or
 More than one sex partner.
• People who have had any of the following in the past 6 months :
 Sex at a commercial sex venue; or
 Sex in association with a large public event in a geographic area where mpox transmission is occurring.
• Sexual partners of people with the above risks.
• People with HIV†infection or other causes of immunosuppression who have had recent or anticipate potential
mpox exposure
• People in certain occupational exposure risk groups (laboratory personnel working with orthopoxviruses)
*People at risk for occupational exposure to orthopoxviruses include research laboratory personnel working with orthopoxviruses, clinical laboratory personnel performing diagnostic testing for orthopoxviruses,
and orthopoxvirus and health care worker response teams designated by appropriate public health and antiterror authorities. (see ACIP recommendations).
†JYNNEOS is considered safe in persons with HIV infection, although effectiveness may be lower among severely immunocompromised individuals. ACAM2000 should not be used in certain people, including those
with advanced HIV disease or other causes of immunosuppression, who are pregnant, or who have certain heart conditions.

         CDC Health Equity Considerations Utilized in Mpox
National Vaccination Strategy
• Engage people from affected communities in planning and design
• Use non-stigmatizing, plain language
• Reiterate privacy of information and how data will be used
• Engage diverse partners already working with special populations
• Bring vaccines to where people are: pop-up events, mobile outreach
• To improve accessibility, offer multiple opportunities and times
• Leverage clinical venues: STI clinics, LGBTQ+ health centers
• Use multiple channels to advertise and book appointments
• Minimize systems that are first-come, first-served
Mpox Vaccine Equity Toolkit | Mpox | Poxvirus | CDC

        Doses administered 100,000
80,000
60,000
40,000
20,000 120,000
5/22-5/28
5/29-6/4
6/5-6/11
6/12-6/18
6/19-6/25
6/26-7/2
7/3-7/9
7/10-7/167/17-7/237/24-7/30
7/31-8/68/7-8/13
8/14-8/20
8/21-8/27
8/28-9/3
9/4-9/10
9/11-9/17
9/18-9/24
9/25-10/110/2-10/8
10/9-10/15
10/16-10/2210/23-10/29
10/30-11/5
11/6-11/12
11/13-11/19
11/20-11/26
11/27-12/3
12/4-12/10
12/11-12/17
12/18-12/24
12/25-12/31
1/1-1/7
1/8-1/14
1/15-1/211/22-1/28
1/29-2/6 First doses
Second doses EUA for intradermal administration introduced
0           Total JYNNEOS Vaccine Doses Administered and
Reported to CDC as of Feb 7, 2023
1,185,907 doses* administered and reported to CDC since May 20, 2022
                        Vaccine First Doses Administered, by Race/Ethnicity
Data Reported to CDC as of January 31, 2023
White NH Hispanic or Latino Black NH Asian NH Other NH Multiple NH AI/AN NH NH/OPI NH
100% Percent of first doses 90%
80%
70% 60%
50%
40% 30%
20%
10%
0% 7% 9%
7%
16%
61% 8%
7%
19%
62% 8%
13%
23%
51% 7%
13%
23%
51% 7%
12%
22%
51% 7%
12%
24%
51% 7%
12%
24%
49% 6%
12%
26%
48% 7%
13%
26%
47% 12%
23%
51%
Overall
5/22-6/18
6/19-7/16 7/17-8/13
8/14-9/10 9/11-10/8 10/9-11/5 11/6-12/3
12/4-12/31
1/1-1/28

              NH=non-Hispanic, AI/AN=American Indian/Alaska Native, NH/OPI=Native Hawaiian/Other Pacific Islander. W eeks where n<30 are not shown. Does not include recipients of Unknown race/ethnicity.
Source: CDC Immunization Data Lake. Data submitted as of January 31, 2023, 4:00 am ET.
124

             Elements of Mpox Vaccine Implementation in the
U.S. during this Outbreak
• Vaccine strategies and implementation plans were adapted by local jurisdictional health
departments for their specific settings
• Vaccine eligibility criteria were modified as the epidemiology evolved and new scientific findings emerged, and were adjusted for local context
 Examples: Inclusion of sex workers; removing sexual orientation labels from eligibility criteria, reducing potential stigma by allowing participant to self-attest to eligibility
• Recognition that mpox vaccination offered in context of broader prevention activities and sexual health care may increase access and coverage
• Critical role of community organizations as trusted messengers, facilitating increased access to vaccination
• Need dedicated resources for reporting vaccine inventory and administration data
• Require vaccine status, date of vaccination on mpox case reporting or link cases with state immunization inventory system to evaluate vaccine performance
• Include race and ethnicity data on vaccination reports, including on reports shared with CDC

       Implementation challenges and solutions
• Limited vaccine supply at the peak of the outbreak in mid-July when demand was
highest
• EUA for intradermal route of administration increased vaccine supply by 300%
• Limited ability to ship directly to providers
• May to September, shipments limited to 5 per week; by mid Sept, up to 150 shipments/week
• Switch to intradermal administration required skills training and additional supplies
• On average, jurisdictions began to implement within 2-3 weeks of EUA
• Initially, health departments and public clinics were the primary vaccine providers (>50% of all vaccinations)
• Increasing role of STI, HIV care providers, pharmacies

Summary: Mpox Vaccine Implementation and Interim Clinical  Considerations  Rosalind Carter, PhD  Vaccine Task Force  2022 Multinational Mpox Response  Centers for Disease Control and Prevention  Advisory Committee on Immunization Practices  February 22, 2023  www.cdc.gov/mpo x                                                                                Interim Clinical Considerations (ICC) is a living  document  • Continued emphasis on vaccination : Mpox vaccination should…


Mpox 07 Rao 508

National  Center  for Emerging  and Zoonotic  Infectious  Diseases
Evidence to Recommendations Framework:
Vaccination with JYNNEOS During Mpox Outbreaks
Agam Rao, MD
CAPT, US Public Health Service
Poxvirus and Rabies Branch
Centers for Disease Control and Prevention
Advisory Committee on Immunization Practices
February 22, 2023
Evidence  to Recommendations  Framework

    Evidence to Recommendations (EtR) Framework

 Structure to describe information considered in moving from evidence to
ACIP vaccine recommendations
Provide transparency around the impact of additional factors on
deliberations when considering a recommendation

          EtR Domains
EtR Domain Question(s)
Public Health Problem • Is the problem of public health importance?
Benefits and Harms • How substantial are the desirable anticipated effects?
• How substantial are the undesirable anticipated effects?
• Do the desirable effects outweigh the undesirable effects?
Values • Does the target population feel the desirable effects are large relative to the undesirable
effects?
• Is there important variability in how patients value the outcome?
Acceptability • Is the intervention acceptable to key stakeholders?
Equity • What would be the impact of the intervention on health equity?
Feasibility • Is the intervention feasible to implement?
Resource Use • Is the intervention a reasonable and efficient allocation of resources?

     EtR question
Does ACIP recommend the 2-dose* JYNNEOS vaccine series for persons
aged 18 years and older at risk of mpox during an mpox outbreak?§
*Dose 2 administered one month after dose 1
§ Public health authorities determine whether there is an mpox outbreak; a single case may be considered
an mpox outbreak at the discretion of public health authorities. Other circumstances in which a public
health response may be indicated include ongoing risk of introduction of mpox into a community due to
disease activity in another geographic area.

EtR Domain:   Public  Health  Problem

             Timeline of Notable Human Mpox Events* Multinational
outbreak
Imported human cases to UK and US: 3 Imported Imported
cases to UK cases to UK,
and Israel: 3 Singapore: 2
-First human case identified -Rural settings US outbreak from pet prairie dogs (cohoused with infected small mammals from Ghana): 47 cases
Outbreak in Nigeria involving 17 states: 138 cases
1970 2003 2017 2018 2019 2021 2022
*During 1970-2021, mpox was endemic in 9 African countries: Cameroon, Central African Republic, Cote d’Ivoire,
Democratic Republic of Congo, Gabon, Liberia, Nigeria, Republic of Congo, and Sierra Leone; during recent years, there has been a re-emergence of human cases after decades of no reported cases

       U.S. mpox case trends as of February 9, 2023

        Many contacts monitored during investigations and
some secondary cases have occurred
 United States, July 2021: Traveler returning from Nigeria
– 223 contacts monitored
– No high-risk exposures and no secondary transmissions
– Contacts included flight crew and fellow passengers on international and
domestic flights, friends, Ride-share driver
 United Kingdom, 2019 and 2021
– 2019: Healthcare personnel developed mpox
after presumed exposure while changing
bedding of mpox patient
– 2020: Two household contacts of mpox patient developed mpox

 Typical manifestations of mpox
Fro  m Basgoz N  , Brown  CM , Smole  SC , e t al . Case  24-
2022  :  A 31-Year-Old  Man  with  Periana  l and  Penile  Ulcers  ,
Recta  l Pain  , and  Rash  . Epub ahead  of  print  . Copyrigh  t ©
Jun  15  2022  . Massachusetts  Medica  l Society  . Reprinted
with  permission  fro m Massachusetts  Medica  l Society
Above  :  Shared  with  permission  fro m
patients
• Lesions often
perianal and/or
affecting genitals
• Rectal pain
• Abdominal pain
• Rectal bleeding
• Tenesmus
https://www.cdc.gov/mmwr/volumes/71/wr/mm7132e3.htm?s_cid=mm7132e3_w

   Severe manifestations: Ocular lesions, neurologic
complications, myopericarditis, and some mucosal lesions
Left: Keratitis
and conjunctival
ulcer
Complications
associated with
some mucosal
lesions
• Painful or Above:
encephalitis obstructing
rectal, urinary Right:
tract, oral and transverse
myelitis genital lesions
and strictures
• Lesions might expose muscle or
bone
Cole J, Choudry S, Kular S,et al. Monkeypox encephalitis with transverse
myelitis in a female patient. Lancet Infect Dis. 2022 Dec 2:S1473-
Rodriguez-Nava  G, Kadlecik P, Filardo  TD et al. Myocarditis  Attributable  to Monkeypox  Virus
Infection  in 2 Patients,  United  States, 2022.  Emerg Infect  Dis. 2022  Dec;28(12):2508-2512. 3099(22)00741-1.
Cash Goldwasser  S,   Labuda  SM, McCormick  DW et al. (2022  )
Ocular  monkeypox, United  States—July-September  2022  .
MMWR.  2022  Oct
Above: NSR with TWI in inferior and anterolateral leads of ECG. Patient
with mpox and no underlying medical conditions. Other signs and symptoms: SOB, decreased exercise tolerance, elevated Tn (0.35ng/mL reference <0.07 ng/mL) indicating myocarditis

       Severe  manifestations  from uncontrolled viral spread  i n
severely  immunocompromised  patients
Menezes YR, Miranda AB. Severe disseminated clinical
presentation of monkeypox virus infection in an immunosuppressed patient: first death report in Brazil. Rev Soc Bras Med Trop. 2022 Aug 29;55:e0392. Carrubba S, Geevarghese A, Solli E et al. Novel severe oculocutaneous manifestations of human monkeypox virus infection and their historical analogues. Lancet Infect Dis. 2023 Jan 23:S1473-3099(22)00869-6.

     Public health importance
Work group interpretation
Are outbreaks of mpox of public health importance?

EtR Domain:   Benefits  and Harms

       Early Estimates and Population-based, adjusted VE
measures*
 Vaccine performance
– Comparison of incidence between vaccinated and unvaccinated persons in 43 U.S.
jurisdictions: Mpox incidence among unvaccinated was 7.4 (95% CI=6.0-9.1) times that
among persons who received only 1 dose of JYNNEOS vaccine ≥14 days earlier, and 9.6
(95% CI = 6.9–13.2) times that among persons who received dose two ≥ 14 days
earlier
 Population-based, adjusted measures of vaccine effectiveness (VE) using electronic
medical records
– Retrospective, population-based cohort study conducted in Israel; 5 mpox infections
among subjects vaccinated with 1 SC dose and 16 among unvaccinated subjects. VE
for dose 1 was 86% (95% CI = 59-95%)
– Nationwide U.S. case-control study with 1:4 ratio of cases matched to controls;
adjusted VE was 35.8% (95% CI: 22.1-47.1%) for one dose and 66.0% (95% CI: 47.7 -
78.1%) for 2 doses, regardless of vaccination route

      Early Estimates and Population-based, adjusted
VE measures*
 Population-based, adjusted measures of VE using case-control studies
– Case-control study of adult MSM (18-49 years of age) in 12 U.S. jurisdictions;
adjusted VE was 76% (95% CI: 48-89%) for two doses (interim results)
– New York State case-control study of adult male mpox cases matched to STI controls; adjusted VE was 68% (95% CI: 25-86%) for one dose and 89% (95% CI: 44-98%) for two doses (preliminary results)

        PEP effectiveness and infections following single dose
 France: 10% (11 of 108) of those administered JYNNEOS after mpox
exposure became symptomatic with mpox disease soon after vaccination
(IQR 1-6, median 5 days), although clinical course mild among those
persons
 France: Observational study involving people who received single, SC dose; 4% (12 of 276) infected during month after vaccination, none with serious
infection
 NYC: Cohort study of individuals with high-risk exposure; VE was 77% with PEP <14 days after last exposure and 79% with PEP <14 days after first exposure

   Benefits
Work group interpretation
How substantial are the desirable anticipated effects of mpox
vaccine during an outbreak?

      Vaccine Safety: Subcutaneous administration
 During May 22, 2022 –January 13, 2023, a total of 1,125,168 JYNNEOS
vaccine doses were administered. CDC monitored JYNNEOS safety using
VAERS and VSD for vaccine recipients of all ages
 Adverse events (AEs)
– The most common AEs reported were nonserious and included
injection site reactions, consistent with prelicensure studies
– Reported at similar rates for doses received by intradermal and
subcutaneous administration
– Serious adverse events were rare among adults

   Harms
Work group interpretation
How substantial are the undesirable anticipated effects of
mpox vaccine during an outbreak?

Do the desirable effects outweigh the undesirable effects?
Favors intervention Favors comparison Favors both Favors neither Unclear Benefits / Harms
Work group interpretation
What is the balance between the desirable effects relative to
the undesirable effects?

EtR Domain:   Values

          Vaccination values extrapolated from 2022 outbreak data
 Populations at highest risk concerned about mpox
– In August, 53.1% of American Men’s Internet Survey (AMIS) respondents had
concerns about getting mpox
– During October-December, an AMIS survey showed that those with high mpox concern had 3.5 times odds of being vaccinated
 Interest in vaccine high
– During Aug-Nov, >85% of respondents in the American Transformative HIV Study (AMETHST) were interested in vaccine
– During Aug-Dec, 50% of Porter-Novelli survey responders who identified as LGBTQ+ felt that vaccination is important to protect from mpox
– During Oct-Nov, >70% of MSM in a San Francisco survey of persons experiencing homelessness reported that they would accept or have accepted vaccination

 Does  the targe  t population  feel that  the desirable  effects  are large  relative  to
undesirable  effects
No            Probably  no            Uncertain            Probably  ye s          Yes Varies Target population sentiments
Work group interpretation
Does the target population feel that the desirable effects are
large relative to undesirable effects?

  Uncertainty or variability in how much people might
value vaccination
 During 2022 mpox outbreak, willingness to be vaccinated was dynamic,
and dependent on perceived vulnerabilities
 There is clear demand for JYNNEOS vaccination, but many remain unvaccinated for unclear reasons
 Demographics of future outbreaks unclear; unknown if values expressed by population most affected by the 2022 mpox outbreak can be extrapolated to all other populations

           Possib  ly important
  uncertainty  or
  variability             Pr obably  no
importan  t
uncertainty  or
variabilit  y         No impor tant
  uncertainty   or
  variabilit  y                    No kn own
 undesirable
  outcomes

                 Target population sentiments
Work group interpretation
Is there important uncertainty about or variability in how much
people value the main outcomes?
Is there  important  uncertainty  about  or
outcomes vari ability in how much people value the main
Importan  t
uncertaint  y
or variabilit  y

EtR Domain:   Acceptability

   Stakeholder perceptions: Sermo survey of clinicians
 Sermo*: Online community of >1.3 million
clinicians
 July 31 - August 1, 2022 survey results of U.S.
clinicians (n=415): 69% felt U.S. without enough mpox vaccine to handle outbreak
 September 12, 2022 survey of U.S. clinicians
(n=62)
• 66% had treated at least one mpox patient
• 76% knew where a patient could get
JYNNEOS vaccination
• 86% wanted to be able to provide vaccination in their office *
https://app.sermo.com/barometer/unitedstates

 Stakeholder perceptions: Health departments
 Health departments have been requesting JYNNEOS and organizing
vaccination campaigns
https://aspr.hhs.gov/SNS/Pages/JYNNEOS-Distribution.aspx

 Vaccine equity pilot program
 Enabled jurisdictions to request more than
their allotted amount of JYNNEOS vaccine
 Established to
– Support innovative ways to address
vaccination disparities
– Encourage vaccination coordination between health departments and community-based organizations
– Promote innovation to strengthen existing vaccination infrastructure

     Acceptability
Work group interpretation
Is the intervention acceptable to key stakeholders

                                               Is the intervention acceptable to key stakeholders
No Probably no Uncertain Probably yes Yes Varies
EtR Domain:   Resource  Use

      Resource Use
 JYNNEOS vaccine is provided from HHS’ Strategic National Stockpile (SNS)
free-of-charge
 Vaccines are a good use of resources during an outbreak
 Costs and challenges associated with mobile, pop-up vaccination sites
 Cost-effectiveness analysis of vaccine implementation during the current outbreak planned, but not currently available

        Resource Use
Work group interpretation
Is the intervention a reasonable and efficient allocation of
resources

                                               Is the intervention a reasonable and efficient allocation of resources
No Probably no Uncertain Probably yes Yes Varies
EtR Domain:   Equity

   Equity
 No groups or settings disadvantaged by recommendation for JYNNEOS use
during mpox outbreaks
 Effectiveness same for all immunocompetent persons
 Implementation to assure equitable access will be important particularly among persons who are at high risk for severe outcomes
 Might facilitate broad acceptance of the recommendation (e.g., by insurance companies, health departments) because endorsed by ACIP after rigorous review of evidence

                                                      Equity
Work group interpretation
What would be the impact on health equity
What would be the impact on health equity?
Reduced Probably Reduced Probably no impact
Increased Varies Don’t know Probably increased

EtR Domain:   Feasibility

     Feasibility
 Feasibility of conducting vaccine campaigns in communities, at events,
and within public health facilities demonstrated in 2022
 Can be integrated into providers’ practices
– Standing orders available
– Immunization Information Systems requirements for reporting vaccinations
same as COVID-19 vaccines
– JYNNEOS can be stored refrigerated for 8 weeks
 Wide range of vaccinators can administer JYNNEOS

    WG discussions
 JYNNEOS vaccination probably sustainable during outbreaks
 Vaccine access is an important concern
– Increased and convenient access
– Low stigma
 Considerations to ensure vaccine equity
– Strong ties with community-based organizations
– Support vaccination events
– Engage trusted messengers
– Ensure access (including in rural areas)

                                                  Feasibility
Work group interpretation
Is the intervention feasible to implement?
Is the intervention feasible to implement
No Probably no Uncertain Probably yes Yes Varies

 Summary of EtR #1
Domains Domains Domains
Benefits: How
substantial are the desired
anticipated effects Large Values: Does the
target population feel desirable
effects are large Probably
Yes Impact on health equity Probably increase d
Harms: How substantial are undesirable
anticipated
effects? Small Is there important uncertainty about or variability in
values? Possibly
important uncertainty
or
variability Feasible to implement? Yes
Benefit / Harm: Favors intervention Acceptable to stakeholders? Yes Balance of consequences:
Overall certainty of the evidence for the critical
outcomes Moderate Reasonable and
efficient allocation of resources? Varies

                       Undesirable
consequences  probab  ly
outweigh  desirable
consequences  in most
settings

             Balance of Consequences
Undesirable
consequences  clear  ly
outweigh  desirable
consequences  in mos  t
settings Balance  between
   desirable  and undesirable
   consequences  is close  ly
 balanced  or uncertain
Desirable  consequence  s
probably  outweigh
undesirable  consequence  s
in mos  t setting  s                    X  Des irable  consequences
 clearl  y outweig  h
 undesirable  consequence  s
 in mos  t settings There  is insufficient  evidence
to determine  the balance  of
  consequences

     Proposed wording
ACIP recommends the 2-dose* JYNNEOS vaccine series for persons
aged 18 years and older at risk of mpox during an mpox outbreak§
*Dose 2 administered one month after dose 1
§ Public health authorities determine whether there is an mpox outbreak; a single case may be considered
an mpox outbreak at the discretion of public health authorities. Other circumstances in which a public
health response may be indicated include ongoing risk of introduction of mpox into a community due to
disease activity in another geographic area.

       Clinical Considerations
 In outbreak setting, vaccine is ideally given pre-exposure but may also be
given as post-exposure prophylaxis (PEP) , although evidence not been
reviewed by ACIP for PEP at this time
 Complete 2-dose vaccine series should be given regardless of timing of exposure
 Although ACIP has not reviewed the evidence, if there are vaccine supply shortages, ID route of administration can be used

                Tentative timeline for ACIP discussions and votes*
Current  U S mpox vaccination  strateg  y remains  active  :  Populations
3Curreantt   hUi.Sg. h  mripsoxk  vsahccoinulatid  ocn ostntriatneugy e  treo  mbaie  nsv ian cecfifnecatted
February 2023 June 2023 October 2023
*February 2023 and June 2023 votes do not impact existing recommendations for the current mpox outbreak.
3https://www.cdc.gov/poxvirus/monkeypox/interim-considerations/overview.htmlMpox  outbreaks:  Use of 2-
dose  JYNNEOS for person  s
aged  ≥ 18 years Mpox  outbreaks:  Use of 2-dose  JYNNEOS
for persons  aged  <18 year  s
-Updates  about vaccine  effectiveness  an d
safetyCo nsider  need  for longer  ter  m
vaccination  strategy for 2-dose
JYNNEOS

 Acknowledgements
 Amanda  Cohn
 Rosalind Carter
Kevin Delaney

 Catherine McLean
 Faisal Minhaj
 Sascha  Ellington
 Jonathan  Duffy
 Dani Moulia
 Anna  Chard
 Manisha  (Mo)  Patel   Adam Cohen  Saskia Voss
 Tom Shimabukuro  Dan Payne
 Rita Helfand  Michael Yeh
 Melinda Wharton  David Hopkins
 Emily Mosites  Brett Petersen
 Dan Filardo  Jane Zucker
 Grace Marx  Jennifer Rosen
 Amy Lansky  Eli Rosenberg
 Rachel Kachur  Sara Oliver
 Christine Prue  Robbie Goldstein

         Questions?
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.
National  Center  for Emerging  and Zoonotic  Infectious Diseases
Division  of High-Consequenc  e Pathogens  and Pathology

Summary: National  Center  for Emerging  and Zoonotic  Infectious  Diseases  Evidence to Recommendations Framework:  Vaccination with JYNNEOS During Mpox Outbreaks  Agam Rao, MD  CAPT, US Public Health Service  Poxvirus and Rabies Branch  Centers for Disease Control and Prevention  Advisory Committee on Immunization Practices  February 22, 2023  Evidence  to Recommendations  Framework                                 Evidence to Recommendations (EtR) Framework     Structure to describe information…


influenza 01 Talbot 508

Seasonal Influenza Vaccines
H. Keipp Talbot , MD, MPH
Chair, Influenza Work Group
Advisory Committee on Immunization Practices
February 22, 2023
Influenza Work Group

 Session Overview


influenza 02 Grohskopf 508

U.S. Influenza Activity
Lisa Grohskopf
Advisory Committee on Immunization Practices
February 22, 2023
Virologic Surveillance
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   For more information, contact CDC
1
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TTY: 1-888-232-6348 ww
w.cdc.gov
Th
e 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.

Summary: U.S. Influenza Activity  Lisa Grohskopf  Advisory Committee on Immunization Practices  February 22, 2023  Virologic Surveillance [ \ ] ^ _ ]`[ \ ] ` _ ] a[ \ ] a _ [ \[ \ [ ] _ [[[ \ [ [ _ [ b [ \ [ \_ [ ]c d e f g h d i jf f k f g h l g m n o o p q pf f k r s t u v w x y                                           For more information, contact CDC  1 -800-CDC-INFO (232-4636)  TTY: 1-888-232-6348 ww w.cdc.gov  Th e findings and conclusions in this report are those of the authors and do not…


influenza 03 Olson Lewis Tenforde 508

nlzation & Respi
Interim Influenza Vaccine Effectiveness against
Inpatient, Emergency Department, and Outpatient
Illness in the 2022-23 season
Data from the New Vaccine Surveillance Network (NVSN),
Flu and Other Viruses in the Acutely Ill Network (IVY),
& VISION Network
Samantha Olson MPH, Nathaniel Lewis PhD, & Mark Tenforde MD PhD
Advisory Committee on Immunization Practices
February 22, 2023

   For more information, contact CDC
1
-800-CDC-INFO (232-4636)
TTY: 1-888-232-6348 ww
w.cdc.gov
Th
e 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.

Summary: nlzation & Respi  Interim Influenza Vaccine Effectiveness against  Inpatient, Emergency Department, and Outpatient  Illness in the 2022-23 season  Data from the New Vaccine Surveillance Network (NVSN),  Flu and Other Viruses in the Acutely Ill Network (IVY),  & VISION Network  Samantha Olson MPH, Nathaniel Lewis PhD, & Mark Tenforde MD PhD  Advisory Committee on Immunization Practices  February 22, 2023                                            For more information, contact CDC  1…


influenza 04 Mclean 508

Marshfield Clinic Research InstituteInterim Estimates of 2022─23 Influenza Vaccine Effectiveness from
Two Studies in Wisconsin: A Test -Negative Case- Control Study and a
Community Cohort Study
ACIP Meeting | February 22, 2023
Huong McLean presenting on behalf of the study team
Marshfield Clinic Research Institute received support for this study from CSL Seqirus and CDC
(75D30120C09259)
Test-negative case- control study
2
•Enrollees: Outpatients aged 6 months –64 years with acute respiratory illness
with cough ≤7 days duration
•Dates of enrollment: December 2, 2022 –February 10, 2023
•Nasal and oropharyngeal swabs tested for influenza and SARS -CoV-2
•Vaccination status: documented (in health record) receipt ≥14 days before
illness onset per ACIP recommendations
•Analysis: VE = (1 –adjusted OR) x 100%
‒Logistic regression model adjusted for age, month of onset, higher -risk condition
(self report)Methods: Test- negative case -control study
3
RT-PCR results by week of enrollment
4 1 patient was positive for both influenza and SARS -CoV- 2 and represented above as separate counts (week ending 12/24/2022)
•34/34 sequenced A(H3N2)
viruses belonged to subclade 2a2
•9/9 A(H1N1pdm09) belonged to subclade 5a.2

Participant* characteristics
5Total no. of
patientsNo. (%)
vaccinated †No. (%)
influenza positiveNo.(%) i nfluenza -and
SARS -CoV-2 negative
Total 545 186 (34) 116 (21) 249 (79)
Age 6 mos – 17 years 223 69 (31) 42 (19) 181 (81)
18 – 64 years 322 117 (36) 74 (23) 248 (77)
Sex Female 318 127 (40) 65 (20) 253 (80)
Male 227 59 (26) 51 (22) 176 (78)
Race/ethnicity Non -Hispanic White 482 161 (33) 105 (22) 377 (78)
Hispanic 35 12 (34) 6 (17) 29(83)
Non -Hispanic non- White 28 13 (46) 5 (18) 23 (82)
Self report of higher -
risk condition§Yes 154 69 (45) 30 (19) 124 (81)
No 391 117 (30) 86 (22) 305 (78)
Self report of ≥2 COVID -
19vaccine doses Yes 258 133 (52) 51 (20) 207 (80)
No 287 53 (18) 65 (23) 222 (77)
*109 patients had a positive test result for SARS -CoV- 2 virus infection and were excluded.
†84% received cell -culture based vaccine (ccIIV4).
§Based on self -report of asthma or another chronic lung disease, cancer, diabetes, heart disease including high blood pressure, i mmunocompromising
condition, kidney disease, liver disease, obesity, and pregnancy in the 12 months preceding enrollment.
Vaccine effectiveness (VE) against outpatient influenza,
children and adults aged 6 months – 64 years
6Influenza positiveInfluenza -and
SARS -CoV-2 negativeAdjusted VE*
No. vaccinated /
Total%No. vaccinated /
Total% % (95% CI)
Influenza A 26 / 116 22 160 / 429 37 54 (23- 73)
A(H3N2) 16 / 86 19 160 / 429 37 60 (25- 79)
Study period: December 2, 2022 – February 10, 2023.
*VE was estimated using the test- negative design as 100% x (1 –aOR) where aOR represents ratio of odds of being vaccinated among influenza positive
cases to odds of being vaccinated among influenza -negative and SARS -CoV- 2-negative controls; ORs were estimated using logistic r egression with
adjustment for age, month of illness onset, and presence of one or more higher -risk condition.
Prospective community cohort study
7
•Ongoing community cohort in central Wisconsin
•241 children aged 1 –1 7 years followed weekly since September 5, 2022
•Weekly reporting for absence or presence of symptoms
Fever, cough, loss of smell or taste, sore throat, muscle/body aches, shortness of breath,
diarrhea, nasal congestion/runny nose, or nausea/vomiting
•New symptom onset prompts self- o r guardian -collection of anterior nasal
swab for influenza and SARS -CoV-2 testing
•Information collected from surveys and extracted from electronic health
r
ecords (e.g., vaccination history, clinical influenza test results)Methods: Community cohort study
8
•Influenza case: positive RT -PCR influenza result (research or clinical sample)
•VE = 𝟏𝟏−𝐚𝐚𝐚𝐚𝐚𝐚𝐚𝐚𝐚𝐚𝐚𝐚𝐚𝐚𝐚𝐚 𝑯𝑯𝑹𝑹𝒓𝒓𝒓𝒓𝒓𝒓𝒓𝒓𝒐𝒐𝒐𝒐𝒊𝒊𝒊𝒊 𝒐𝒐𝒊𝒊𝒊𝒊𝒓𝒓𝒊𝒊𝒊𝒊𝒓𝒓𝒊𝒊𝒊𝒊𝒐𝒐𝒓𝒓𝒊𝒊𝒓𝒓𝒊𝒊 𝒐𝒐𝒊𝒊𝒓𝒓𝒂𝒂𝒐𝒐 𝒊𝒊 𝒂𝒂𝒗𝒗𝒓𝒓𝒊𝒊 𝒊𝒊𝒊𝒊𝒊𝒊𝒓𝒓𝒓𝒓𝒓𝒓𝒗𝒗𝒑𝒑𝒓𝒓 𝒓𝒓𝒑𝒑𝒐𝒐 𝒊𝒊−𝒓𝒓𝒊𝒊 𝒂𝒂𝒓𝒓
𝒓𝒓𝒓𝒓
𝒓𝒓𝒓𝒓𝒐𝒐𝒐𝒐𝒊𝒊𝒊𝒊
𝒐𝒐𝒊𝒊𝒊𝒊𝒓𝒓𝒊𝒊𝒊𝒊𝒓𝒓𝒓𝒓𝒂𝒂𝒐𝒐
𝒊𝒊
𝒂𝒂𝒊𝒊
𝒊𝒊𝒗𝒗𝒓𝒓𝒊𝒊𝒊𝒊𝒊𝒊𝒊𝒊𝒓𝒓𝒓𝒓𝒓𝒓𝒗𝒗 𝒑𝒑𝒓𝒓
𝒓𝒓𝒑𝒑𝒐𝒐
𝒊𝒊−𝒓𝒓𝒊𝒊
𝒂𝒂𝒓𝒓∗𝟏𝟏𝟏𝟏𝟏𝟏𝟏
•A
djusted for age, higher -risk condition (self -report), COVID -19 vaccination Analysis: Community cohort study
9At risk October 23, 2022 –February 10, 2023 or positive influenza infection date
Vaccinated ≥14 days after influenza vaccine receipt*
Unvaccinated Time before influenza vaccination
Censored Person -time for the 13 days after vaccine receiptCox proportional hazards model with time- varying vaccination status
*Based on documentation in health record according to ACIP recommendations
Characteristics of community cohort
10Total no. of
participants*No. (%)
vaccinated †No. (%)
influenza positive¶
Total 241 94 (39) 34 (14)
Age 1 –8 years 71 31 (44) 9 (13)
9 –17 years 170 63 (37) 25 (15)
Sex Female 116 49 (42) 17 (15)
Male 125 45 (36) 17 (14)
Race/ethnicity Non -Hispanic White 233 92 (39) 33 (14)
Hispanic 2 2 (100) 1 (50)
Non -Hispanic non- White 6 0 (0) 0 (0)
Self report of higher -risk
condition§Yes 31 13 (42) 6 (19)
No 210 84 (39) 28 (13)
≥2 COVID -19vaccine doses Yes 115 61 (53) 20 (17)
No 126 33 (26) 14 (11)
*242 participants enrolled; 1 was excluded because they were partially vaccinated per ACIP recommendations prior to the start ofthe analysis period.
†84% received cell -culture based vaccine (ccIIV4).
¶3 cases occurred ≤14 days from influenza vaccination and were censored at the time of vaccination.
§Based on self -report of asthma, immunocompromised state, serious heart condition, or other chronic lung disease.
Influenza and SARS -CoV-2 infections by week of onset
11
•6/6 sequenced A(H3N2)
viruses belonged to subclade 2a2

Vaccine effectiveness (VE) against symptomatic influenza among children
12No. of
influenza
infections *No. of
person -daysIncidence per 1,000
person -daysAdjusted VE†
% (95% CI)
Vaccinated 6 7,292 0.8271 (31 ‒ 90)Not Vaccinated 28 15,678 1.79
Study period: October 23, 2022 – February 10, 2023.
*3 influenza infections were censored because onset occurred within 14 days of vaccination.
† VE was estimated from Cox proportional hazards model with time -varying influenza vaccination status, age, presence of at least o ne higher -risk condition
(self -report of asthma, immunocompromised state, serious heart condition, or other chronic lung disease), and receipt of 2 or mo re COVID -19 vaccine
doses before the analysis period.
•Single geographic area (central WI)




Predominant viruses similar in study population and across US
•Adults aged ≥6 5 years excluded
Generally have lower VE estimates against A(H3N2)
•Small sample sizes
Wide confidence intervals
Unable to estimate VE for A(H1N1)pdm09 or age groups
•Confounding and bias with observational studies
Comparable estimates across two study designsLimitations
13
•Interim results indicate substantial vaccine- induced protection against
influenza A during 2022 -23 season
‒VE 54% against medically attended influenza A in children and working aged
adults
‒VE 71% against symptomatic influenza A in children
•All characterized viruses from the study population belonged to the same
genetic subclade as the viruses included in the 2022 –23 Northern Hemisphere
influenza vaccineSummary
14
Jennifer King
Carla Rottscheit
Adam Bissonnette
Gina Burbey
Liz Armagost
Brooklyn Arbs
Saydee Benz
Riley Bonifer
Bobbi Bradley
Michaela Braun
Brianna Breu
Corey -Beth Cielinski
Christian Delgadillo
Leila Deering
Heather Dirkx
Roxy Eibergen
Alex Ermeling
Kelsey Ewert
Kallie Falteisek
Rachel Fernandez Hope Florence
Sandy Freeman
Wayne Frome
Tammy Gault
Emily Gruenling
Sherri Guzinski
Angela Harless
Mitch Hertel
Garrett Heuer
Lee Jepsen
Julie Karl
Burney Kieke
Stephanie Kohl
Sarah Kohn
Diane Kohnhorst
Sarah Kopitzke
Tamara Kronenwetter Koepel
Erik Kronholm
Kate Lassa
Thao LeAlaura Lemieux
Carrie Marcis
Megan Maronde
Dave McClure
Isaac McCready
Andrea McGaver
Karen McGreevey
Nidhi Mehta
Laura Michalik
Vicki Moon
Jennifer Moran
Mike Owens
DeeAnn Polacek
Martha Presson
Nicole Price
Maxine Racanelli
Chris Rayburn
Miriah Rotar
Jesse Rozmarynowski
Jackie SalzwedelJuan Saucedo
Kelly Scheffen
Alex Slenczka
Jacob Solis
Elisha Stefanski
Melissa Strupp
Lyndsay Watkins
Providers, managers,
and clinical staff at:
Marshfield Clinic Lake Hallie
Center
Marshfield Clinic Wausau Center
Marshfield Medical Center -
Eau Claire
Marshfield Medical Center -
Marshfield
Marshfield Medical Center -
WestonAcknowledgements
15
Edward Belongia*
 Joshua Petrie*
 Kayla Hanson*
 Jennifer Meece*Marshfield Clinic Health System
Gregg Sylvester*
Karita Ambrose
Ashesh Gandhi
Mendel HaagCSL Seqirus
Melissa Rolfes*
Brendan Flannery
Jessie ChungCDC
Gabriele Neumann*
Yoshihiro Kawaoka *
David PattinsonUniversity of
Wisconsin – Madison
*Coauthor

Summary: Marshfield Clinic Research InstituteInterim Estimates of 2022─23 Influenza Vaccine Effectiveness from  Two Studies in Wisconsin: A Test -Negative Case- Control Study and a  Community Cohort Study ACIP Meeting | February 22, 2023 Huong McLean presenting on behalf of the study team Marshfield Clinic Research Institute received support for this study from CSL Seqirus and CDC  (75D30120C09259)  Test-negative case- control study 2 •Enrollees: Outpatients aged 6 months –64 years with acute…


influenza 05 Grohskopf 508

National Center for Immunization & Respiratory Diseases
Published Estimates of LAIV Effectiveness
Lisa Grohskopf
Advisory Committee on Immunization Practices
February 22, 2023
Update on Published Estimates of LAIV4 Effectiveness: Background
LAIV4 not recommended in the U.S. for 2016 -17 and 2017- 18, following
observation of poor effectiveness against H1N1pdm09 viruses.
Subsequent studies suggested poor replicative fitness of the LAIV4 H1N1pdm09 -
l
ike vaccine virus, which was subsequently updated.
LAIV4 again a recommended option starting in 2018- 1 9 after discussion of
–Combined U.S. individual level patient VE analysis,
–Systematic review of post -2 009 US/non- US LAIV VE estimates,
–MedImmune d ata suggesting better fitness of new H1N1pdm09 vaccine virus.
LAIV4 use within CDC U.S. VE networks has been low since 2018 -1 9, precluding
assessment of vaccine- specific VE.
LAIV VE estimates have been published from non- U .S. observational studies.
2
Vaccine Effectiveness, %
* Report notes that 92% in 2 -6y age group received LAIV4; the remainder offered IIV4.362018- 19
3654
49536871
4572
646373
-4Published Non- US VE
Estimates
All influenza viral
types/subtypes
1. Stuurman et al  Vaccine
2020;
38:6455-6463
2. Pebody, Vaccine 38 (2020) 489–4
3. Stuurman et al  Vaccine 2021;
39:3964-3973
4. https://webarchive.nationalarchive
s.gov.uk/ukgwa/20220401215804/
https://www.gov.uk/government/s
tatistics/annual -flu-reports
5. https://www.gov.uk/government/s
tatistics/annual -flu-
reports/surveillance -of-influenza -
and- other -seasonal -respiratory -
viruses-in -winter -2021- to-2022
6. Emborg ,  Euro Surveill
2022;27:pii=2200278LAIV4 IIV4
All vaccines
FIN    FinlandUK     United Kingdom
DEN    Denmark
0102030405060708090
FIN (1)
LAIV4
2-6yFIN (1)
IIV4
6m-6yUK (2)
LAIV4
2-17yUK (2)
all vaccines
2-17yFIN (3)
LAIV4
2-6yFIN (3)
IIV4
6m-6yUK (4)
LAIV4
2-17yUK (5)
LAIV4
2-17yUK (5)
all vaccines
1-17yDEN (6)
all
vaccines*
2-6y
non-hospDEN (6)
all
vaccines*
2-6y
hosp2019- 20 2021- 22
4
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 o f 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: National Center for Immunization & Respiratory Diseases Published Estimates of LAIV Effectiveness Lisa Grohskopf Advisory Committee on Immunization Practices February 22, 2023 Update on Published Estimates of LAIV4 Effectiveness: Background LAIV4 not recommended in the U.S. for 2016 -17 and 2017- 18, following  observation of poor effectiveness against H1N1pdm09 viruses. Subsequent studies suggested poor replicative fitness of the LAIV4 H1N1pdm09 - l ike vaccine virus, which was subsequently…


Pneumococcal 01 Poehling 508

Pneumococcal Vaccines
Katherine A. Poehling, MD, MPH
Pneumococcal Vaccines Work Group Chair
Advisory Committee on Immunization Practices
February 22, 2023

     Pneumococcal Vaccines Work Group
ACIP Members
• Katherine Poehling (Chair)
• Sarah Long
Ex Officio Members • Jeffrey Kelman (CMS)
• Lucia Lee (FDA)
• Tina Mongeau (FDA)
• Uzo Chukwuma (IHS)
• Mamodikoe Makhene (NIH)
CDC Lead
• Miwako Kobayashi (NCIRD) Liaison Representatives and Consultants
• Lynn Fisher (AAFP)
• Mark Sawyer (AAP/COID)
• Jason Goldman (ACP)
• David Nace (AGS/AMDA)
• Aleksandra Wierzbowski (NACI)
• James McAuley (IDSA)
• William Schaffner (NFID)
• Virginia Caine (NMA)
• Monica Farley (VAMC/Emory)
• Keith Klugman (BMGF)
• Arthur Reingold (UC Berkley)
• Lorry Rubin (CCMC)
• Richard Zimmerman (U. of Pittsburgh)

 Pneumococcal Vaccines Work Group
CDC Contributors
• Adam Cohen (Respiratory Diseases Branch)
• Ryan Gierke (Respiratory Diseases Branch)
• Jennifer Farrar (Respiratory Diseases Branch)
• Pedro Moro (Immunization Safety Office)
• Liz Velazquez (Immunization Services Division)
• Marc Fischer (Arctic Investigations Program)
• Noele Nelson (Division of Bacterial Diseases)
• Jessica MacNeil (ACIP Secretariat)
GRADE/EtR consultants
• Doug Campos-Outcalt
• Rebecca Morgan

  Pneumococcal vaccines currently recommended for
use in the United States
Recommended for
children Recommended for adults
Pneumococcal conjugate vaccines
PCV13
PCV15
PCV20
Pneumococcal polysaccharide vaccine PPSV23 Risk-based
recommendations If previously received PCV13 or PCV15

       All children under age 2 years have the same
pneumococcal vaccine recommendations
• 3 primary series and a booster=“3+1” schedule
PCV PCV PCV PCV 2months 4months 12–15 months 6months
Primary Series Booster
Either PCV13 or PCV15 can be used for U.S. children.

 Children with certain underlying conditions are recommended
to receive PPSV23 in addition to the recommended PCV doses
PPSV23 Recommended
PCV doses Recommended
PCV doses Healthy
children
CMC, CSF leak,
cochlear
implant
≥8 weeks
Recommended
PCV doses PPSV23 PPSV23 Immuno-
compromised
≥8 weeks ≥5 years
CMC aged 6–18
years PPSV23

  Note: Excludes catch-up vaccination schedules.
CMC=chronic medical conditions, including chronic heart disease, chronic lung disease, diabetes mellitus
CSF=cerebrospinal fluid
Use of 15-Valent Pneumococcal Conjugate Vaccine Among U.S. Children: Updated Recommendations of the Advisory Committee on Immunization
Practices — United States, 2022 | MMWR (cdc.gov)

2022 2023 February 2023
Pediatric PCV20 use approval
anticipated Q2 2023
Pediatric PCV15 use
June 2022 approved Approval of PCV20 use among Children Anticipated in 2023

       U.S. FDA Accepts for Priority Review the Supplemental Biologics License Application for Pfizer’s 20-Valent Pneumococcal
Conjugate Vaccine in Infants and Children | Pfizer

 Policy questions considered by the Work Group
• Should PCV20 be recommended as an option for pneumococcal
conjugate vaccination according to currently recommended dosing
and schedules, for U.S. children aged <2 years ?
• Should PCV20 without PPSV23 be recommended as an option for
pneumococcal vaccination for U.S. children aged 2–18 years with
underlying medical conditions that increase the risk of
pneumococcal disease?

        Today’s Pneumococcal Vaccines session outline
Introduction Dr. Katherine Poehling
(ACIP , WG Chair)
Epidemiology of pneumococcal disease among U.S. children Mr. Ryan Gierke (CDC/NCIRD)
Pediatric outpatient ARI visits and antibioticattributable to serotypes in higher valency PCVs use Ms. Laura King (U.C. Berkeley)
PCV20 phase 2/3 study results among children Dr. Wendy Watson
(Pfizer)
Preliminary EtR for PCV20 use in U.S. children Dr. Miwako Kobayashi
(CDC/NCIRD)
Work Group considerations and next steps Dr. Miwako Kobayashi
(CDC/NCIRD)

Summary: Pneumococcal Vaccines  Katherine A. Poehling, MD, MPH  Pneumococcal Vaccines Work Group Chair  Advisory Committee on Immunization Practices  February 22, 2023                                                                                Pneumococcal Vaccines Work Group  ACIP Members  • Katherine Poehling (Chair)  • Sarah Long  Ex Officio Members • Jeffrey Kelman…


Pneumococcal 02 Gierke 508

National Center for Immunization & Respiratory Diseases

    Current Epidemiology of Pediatric Pneumococcal
Disease, United States
Ryan Gierke, MPH
Advisory Committee on Immunization Practices
Feb 22, 2023
1

 Pneumococcal carriage is precursor to pneumococcal disease
Noninvasive Disease
Invasive Disease More frequent
Less frequent
Bogaert, Lancet Infect Dis 2004;4:144-54 2

  Outline
 Invasive Pneumococcal Disease (IPD) in children
• Impact of Pneumococcal Conjugate Vaccines (PCVs) on IPD incidence and
serotype distribution
• IPD incidence caused by serotypes in PCV15 and PCV20
• Changes in IPD incidence and serotype distribution post-COVID19
 Acute Otitis Media (AOM)
• Impact of PCV13
• Incidence Estimates
 Pneumonia in children • Impact of PCV13 on all-cause and pneumococcal pneumonia
• Incidence Estimates
3

   Impact of PCVs on Invasive Pneumococcal Disease
(IPD) Incidence and Serotype Distribution among
Children in the U.S.
4

         Methods
 Active Bacterial Core surveillance (ABCs):
 Active laboratory and population-based
surveillance, 10 sites
 Pneumococcus isolation from sterile site
 Isolates serotyped by whole genome sequencing, Quellung, or PCR at reference labs and grouped for analysis by vaccine type
 US Census Bureau race-bridged post-census population estimates used as denominators
 Overall and serotype-specific IPD incidence rates (cases per 100,000 people)
5

 Incidence rates of invasive pneumococcal disease (IPD) among children < 5
years old, 1998–2019
0 10 20 30 40 50 60 70 80 90 100 Cases per 100,000 persons All IPD PCV13+6C Non-PCV13 PCV7 introduction
PCV13 introduction
children *
1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019
Year
                *Serotype 6C was grouped with PCV13 serotypes due to cross protection from 6A antigen in the vaccine 6

 Incidence rates of invasive pneumococcal disease (IPD) among children < 5
years old, 2007 – 2021
25
20 15
10
5
0
2007 2008 2009 2010 2011 2012 2013 2014
Year 2015 2016 2017 2018 2019 2020 2021 Cases per 100,000 ALL IPD
PCV13 + 6C
Non-PCV13 PCV13: children
COVID-19 *
                7
*Serotype 6C was grouped with PCV13 serotypes due to cross protection from 6A antigen in the vaccine
Incidence rates of IPD among children < 5 years old, 2011 – 2021,
by PCV13+6C*serotypes
2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021
Year 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 Cases per 100,000 population 001 005
PCV7 (except 19F) 19F
06C 003
07F 19A % of PCV13+6C serotypes
2018-2019 2020-2021
003 46% 18%
19F 32% 60%
19A 14% 18%
06C 4% 0%
COVID-19

                *Serotype 6C was grouped with PCV13 serotypes due to cross protection from 6A antigen in the vaccine 8

    Current Pediatric Pneumococcal Disease Incidence Caused by
Serotypes in PCV15 and PCV20
9

        Serotypes contained in current and new pneumococcal
vaccines
1 3 4 5 6A 6B 7 F 9V 14 18
C 19
A 19 F 23 F 22 F 33 F 8 10 A 11 A 12 F 15 B 2 9N 17
F 20
PCV13
PCV15 PCV20 PPSV23
For analysis purposes:
• PCV13+6C : includes serotype 6C with PCV13 types due to cross
protection from 6A antigen
• PCV15 non-PCV13 : includes serotypes 22F and 33F
• PCV20 non-PCV15 : includes serotypes 8, 10A, 11A, 12F, and 15B
• PPSV23 non-PCV20 : includes serotypes 2, 9N, 17F, and 20
10
Incidence rates of IPD among children <5 years old,
2011 – 2021, by vaccine type
14
12 10
8 6 4 2
0
2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 PCV13+6C PCV15/ non-PCV13 PCV20/ non-PCV15
PPSV23/ non-PCV20 Non-Vaccine Type
COVID-19 Proportion of IPD
2018-2019 2020-2021
Non-Vaccine Type 46% 52%
PPSV23/ non-PCV20 1% 4%
PCV20/ non-PCV15 15% 13%
PCV15/ non-PCV13 17% 15%
PCV13+6C 21% 16%

Year Cases per 100,000 population

       PCV15 non-PCV13 serotypes: 22F, 33F P
CV20 non-PCV15 serotypes: 8, 10A, 11A, 12F, 15B
PPSV23 non-PCV20 serotype: 2, 9N, 17F ,20 11

    Incidence rates of IPD among children 5 -18 years old,
2011 – 2021, by vaccine type Cases per 100,000 population
0.0 0.5 1.0 1.5 2.0 2.5
2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 PCV13+6C PCV15/ non-PCV13 PCV20/ non-PCV15
PPSV23/ non-PCV20 Non-Vaccine Type % of IPD
2018-2019 2020-2021
Non-Vaccine Type 32% 36%
PPSV23/ non-PCV20 5% 5%
PCV20/ non-PCV15 13% 16%
PCV15/ non-PCV13 16% 9%
PCV13+6C 34% 34%
COVID-19

       Year
PCV15 non-PCV13 serotypes: 22F, 33F PCV20 non-PCV15 serotypes: 8, 10A, 11A, 12F, 15B PPSV23 non-PCV20 serotype: 2, 9N, 17F ,20 12

 IPD incidence among children with
immunocompromising conditions, 2015-2019*
Children < 5 years Children 5-17 years
10000 10000 Rate Ratio=231
Rate Ratio=29
1 Cases Per 100,000 persons
(Log scale) 1000
Cases Per 100,000 persons
(Log scale) 1000
Rate Ratio=71
100 100
10
Sickle Cell Diseaseˆ 10
1
Hematologic Malignancy Sickle Cell Diseaseˆ
Condition No condition Condition No condition

               CDC
unpublished data, IPD cases identified from ABCs
*Hematologic Malignancy Data only available from 2015-2018 for children age <5 years
ˆ IPD rates for those with and without sickle cell disease are among African American children 13
Acute  Otitis  Media  (AOM) i n Children
14

   PCV13 impact on acute otitis media in children
 AOM is a major cause of childhood morbidity1,2,3
• Pneuococcus is a common bacterial cause of AOM
• S. pneumoniae accounted for an estimated 24%4
 AOM incidence decreased after PCV13 introduction
• 11%-14% decrease, depending on age group and study years1,2
1 Tong et al. BMC 2018
2 King et al. ASHE 2021
3Casey et al Clin Pediatr 2014;
4Kaur et al. EJCMID 2022 15

    Incidence of acute otitis media among children
AOM visits per 100,000 Person Years
20141 2014-20182 2016-20183
<1 43,180 -- --
1 year 47,860 -- --
<2 years -- 76,880 49,050
2-4 years 29,980 41,030 31,970
5-17 years 9,060 9,180 5,680
AOM incidence highest
among children age <5 years
1  Ton  g et  al.  BMC 2018
2  Hu  et  al.  BMC 2022
3Unpublishe  d analysi  s courtesy  o f Laura  King,  U C Berkeley 16

  Pneumonia in Children
17

   Evidence of PCV13 impact on pneumonia in children
 Reduction in incidence of all-cause and pneumococcal pneumonia among in
children following PCV13 introduction1,2,3
• 17-35% reduction in all cause-pneumonia1
• 40% and 51% reduction in inpatient pneumococcal pneumonia among ages <1
and 5-17 years, respectively; no reductions in ages 2-4 years2
1Tong et al. BMC 2018
2 Simonsen et al. Lancet 2014
18 3King et al. ASHE 2021

 Pneumonia incidence among children
Age (years) All-cause pneumonia (frequency per
100,000 person years)1 , 2014 All-cause inpatient pneumonia (cases
per 100,000 population)2 , 2018–19
< 1 2,250 680
1 3,990 480
2–4 3,390 290
5–17 1,280 87
1 Tong et al. BMC 2018
2 National Inpatient Sample, 2018-2019
18

    Conclusions
• Use of PCVs (PCV7, PCV13) significantly decreased the incidence of pneumococcal
disease in U.S. children
• Risk of disease remains higher in children with immunocompromising conditions compared to children without
• In 2018–2019, the proportion of IPD caused by vaccine serotypes was:
• PCV20, non-PCV13: ~30% of IPD
• PCV15, non-PCV13: ~15% of IPD
20

         Questions
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.

Summary: National Center for Immunization & Respiratory Diseases                          Current Epidemiology of Pediatric Pneumococcal  Disease, United States  Ryan Gierke, MPH  Advisory Committee on Immunization Practices  Feb 22, 2023  1                    Pneumococcal carriage is precursor to pneumococcal disease  Noninvasive Disease  Invasive Disease More frequent  Less frequent  Bogaert, Lancet Infect Dis 2004;4:144-54 2                                                           Outline  …


Pneumococcal 03 King 508

Laur  a King,  MPH
Advisor  y Committ  ee o  n Immunizatio  n Practices
Februar  y 22  , 2023 PP PPeeeeddddiiiiaa aattttrrrriiiiccc    c oo oouu uuttttpp ppaaaattttii iiee eenn nnttt  t   AAAARR RRIII  I   vv vvii iissssii iitttts ss  s   aa aannnnddd  d   aa aannnnttttii iibbbbii iioo oott ttiiiic cc  c   uu uusssseee  e
aaaatt tttt ttrrrriiiibb bbuu uuttttaa aabb bblllleee    e tt tto oo  o   ss sseeeerrrroooott ttyyyypp ppeeees ss  s   ii iinnn  n   hhhhii iigg gghhhhee eerrr  r   vvvvaaaallllee eenn nncc ccy yy    y PP PPCC CCVV VVssss

 Disclosures
• Laura King has received consulting fees from Merck for unrelated
work.
• Joseph Lewnard has received consulting fees and grants from Pfizer, Merck, and VaxCyte for related and unrelated work.
• All other authors report no conflicts.
2

 Overview
• Background and study objective
• Pediatric outpatient visit and antibiotic prescription incidence
• Acute otitis media vaccine serotype attributable proportion and incidence
• Sinusitis and pneumonia vaccine serotype attributable proportion and
incidence
• Summary and conclusions
3

 Outpatient respiratory infections: a sizeable
burden
• ~1,200 acute respiratory infection (ARI) visits per 1,000 children in a
commercially-insured population in 20181
• ~250 ARI-associated antibiotic prescriptions per 1,000 children issued from doctor’s offices and emergency departments in the US annually (2014-15)
2
• Limited knowledge of the proportion of ARI visits and antibiotic prescriptions attributable to Streptococcus pneumoniae
1. King LM, et al. Antimicrob Steward Healthc Epidemiol . 2021;1(1):1-8. doi: 10.1017/ash.2021.230.
2. Hersh AL, et al. Clin Infect Dis . 2021;72(1):133-137. doi: 10.1093/cid/ciaa667. 4

         Reductions in antibiotic use concurrent with
PCV uptake
US outpatient oral antibiotic prescriptions per 1,000 persons, 2011-2016
King et al., Clin Infect Dis . 2020; 70(3):370-377). doi: 10.1093/cid/ciz225. 5

        Study objective
Visits and antibiotic prescriptions attributable to additional serotypes in
higher-valency PCVs =
Incidence  o f all -caus  e
pediatric  outpatient visi  ts
and  antibiotic  prescriptions
for  AOM  , pneumonia,  and
sinusitis
 Proportio  n of outpatient
diseas  e caused  by  S.
pneumoniae PCV15 -13  and
PCV20 -13  serotypes*
*PCV15-13/PCV20-13 serotypes: serotypes in PCV15/PCV20 not in PCV13 6
Visits and antibiotic prescriptions attributable to additional serotypes in
higher-valency PCVs =
Incidence  o f all -caus  e
pediatric  outpatient visi  ts
and  antibiotic  prescription  s
for  AOM  , pneumonia,  and
sinusitis Proportio  n of outpatient
diseas  e caused  by  S.
pneumoniae PCV15 -13  and
PCV20 -13  serotypes
7

     All-cause incidence estimation methods

Total incidence = incidence in physician offices and emergency departments +
incidence in all other outpatient settings
8 Setting  Data  source  for  number  of  visits
 and antibiotics  Data  source  for -  person years
 at risk
 Physician offices   NAMCS 2016, 2018    US Census 2016, 2018
 Emergency departments   NHAMCS 2016, 2018    US Census 2016, 2018
  Alternative outpatient
settings   MarketScan Commercial and
  Medicaid Databases 2016-2018   MarketScan Commercial and
  Medicaid Databases 2016-2018

Condition  Outpatient  visits  per  1000
 person-years  (95% CI)  Antibiotic  prescriptions  per
  1000 person-years  (95% CI)
AOM   146 (116, 180)   124 (103, 149)
Sinusitis    40 (27, 58)   39 (24, 60)
Pneumonia   21 (14, 30)   17 (13, 21)
Total   208 (168, 254)   181 (148, 218) All-cause visit and antibiotic prescription
incidence in children by condition
9

Incidence  of pediatric
outpatient  visits  and
antibiotic  prescriptions  fo
AOM,  pneumonia,  and
sinusitisrVisits and antibiotic prescriptions attributable to additional serotypes in
higher-valency PCVs =
Proportio  n of outpatient
diseas  e caused  by  S.
pneumoniae PCV15 -13  and
PCV20 -13  serotypes

10

 Challenges in estimating the proportion of
outpatient disease caused by S. pneumoniae
• Children frequently colonized with pneumococcus
• Samples not regularly obtained from infection site in outpatient
disease
• Few studies conducted for non-AOM ARIs in pediatric outpatients
11

                    cc cii idd dee enn ncc cee eoo off foo ouu utt tpp paa att tii iee enn ntt tAA AOO OMM M PP Prr roo opp poo orr rtt tii ioo onn naa ann ndd d
cc caa auu uss see edd dbb byy yPP PCC CVV V11 155 5-- -11 133 3aa ann ndd dPP PCC CVV V22 200 0-- -11 133 3ss see err roo ott tyy ypp pee ess siinn Proportion and incidence of outpatient AOM
caused by PCV15-13 and PCV20-13 serotypes in
12

         AA AOO OMM MThree approaches to estimating PCV15-13 and
PCV20-13 attributable proportions in AOM
1. Vaccine probe: use vaccine effectiveness against disease associated
with all etiologies to estimate attributable proportion
2. Pneumococcal prevalence and serotype distribution from middle ear fluid in children with AOM
3. Differential nasopharyngeal (NP) carriage between sick and healthy children and NP carriage serotype distribution in children with AOM
13

        AA AOO OMM MAOM pneumococcal and vaccine serotype
attributable percents
AOM attributable percent (95% CI)
Method All pneumococcal
serotypes PCV15-13 serotypes PCV20-13 serotypes
Vaccine probe 16.7 (4.3, 41.9) 0.9 (0.2, 2.3) 4.5 (1.1, 11.5)
Middle ear fluid 22.3 (17.1, 27.5) 1.0 (0.7, 1.4) 5.1 (3.9, 6.4)
Differential NP
carriage 14.0 (2.0, 26.0) 0.7 (0.1, 1.5) 3.7 (0.5, 7.1)
14

        vv vii iss sii itt tss s Estimated pediatric outpatient visits for AOM
attributable to PCV15-13 and PCV20-13 serotypes
Incidence per 1000 person-years (95% CI) Annual number in thousands* (95% CI)
Method PCV15-13 serotypes PCV20-13 serotypes PCV15-13 serotypes PCV20-13 serotypes
Vaccine probe 1.3 (0.3, 3.5) 6.5 (1.6, 17.1) 92 (23, 257) 477 (121, 1,251)
Middle ear fluid 1.5 (1.0, 2.2) 7.4 (5.2, 10.2) 109 (72, 161) 543 (381, 747)
Differential NP
carriage 1.0 (0.1, 2.2) 5.4 (0.8, 10.7) 76 (11, 165) 397 (56, 787)
*Estimated using 2018 census estimate for children <18 years 15

        aa ann ntt tii ibb bii ioo ott tii icc c
pp prr ree ess scc crr rii ipp ptt tii ioo onn nss sEstimated pediatric outpatient antibiotic
prescriptions for AOM attributable to PCV15-13 and PCV20-13 serotypes
Incidence per 1000 person-years (95% CI) Annual number in thousands* (95% CI)
Method PCV15-13 serotypes PCV20-13 serotypes PCV15-13 serotypes PCV20-13 serotypes
Vaccine probe 1.1 (0.3, 3.0) 5.6 (1.4, 14.5) 79 (19, 217) 408 (104, 1,065)
Middle ear fluid 1.3 (0.9, 1.8) 6.3 (4.5, 8.5) 93 (63, 135) 464 (333, 626)
Differential NP
carriage 0.9 (0.1, 1.9) 4.6 (0.7, 9.1) 65 (9, 139) 340 (48, 666)
*Estimated using 2018 census estimate for children <18 years 16

                        PP Prr roo opp poo orr rtt tii ioo onn naa ann ndd dii inn ncc cii idd dee enn ncc cee eoo off foo ouu utt tpp paa att tii iee enn ntt tpp pnn nee euu umm moo onn nii iaa a
aa ann ndd dss sii inn nuu uss sii itt tii iss scc caa auu uss see edd dbb byy yPP PCC CVV V11 155 5-- -11 133 3aa ann ndd dPP PCC CVV V22 200 0-- -11 133 3
ss see err roo ott tyy ypp pee ess sProportion and incidence of outpatient pneumonia
and sinusitis caused by PCV15-13 and PCV20-13
serotypes
17

      pp pnn nee euu umm moo onn nii iaa a
ss sii inn nuu uss sii itt tii iss sTwo approaches to estimating PCV15-13 and
PCV20-13 attributable proportions in pneumonia
and sinusitis
1. Vaccine probe: use vaccine effectiveness to estimate attributable
proportion
2. Differential NP carriage between sick and healthy children and NP carriage serotype distribution in children with AOM
18

Method   All pneumococcal
serotypes  PCV15-13 serotypes  PCV20-13 serotypes
 Vaccine probe   18.2 (12.5, 27.3)   0.9 (0.5, 1.5)   4.4 (2.9, 6.7)
 Differential NP carriage   11.8 (1.0, 22.7)   0.6 (0.0, 1.2)   2.8 (0.2, 5.5) PP Pnn nee euu umm moo onn nii iaa a Pneumonia pneumococcal and vaccine
serotype attributable percents
Pneumonia attributable percent (95% CI)
19

        pp pnn nee euu umm moo onn nii iaa a Estimated pneumonia pediatric outpatient visits
and antibiotic prescriptions attributable to PCV15 -
13 and PCV20-13 serotypes
Incidence per 1000 person-years
(95% CI) Annual number in thousands*
(95% CI)
Outcome Method PCV15-13
serotypes PCV20-13
serotypes PCV15-13
serotypes PCV20-13
serotypes
Vaccine probe 0.2 (0.1, 0.4) 0.9 (0.5, 1.6) 14 (7, 26) 68 (39, 118)
Outpatient visits
Differential NP
carriage 0.1 (0.0, 0.3) 0.6 (0.1, 1.3) 9 (1, 21) 43 (4, 95)
Antibiotic prescriptions Vaccine probe
Differential NP
carriage 0.1 (0.1, 0.3)
0.1 (0.0, 0.2) 0.7 (0.5, 1.2) 0.5 (0.0, 1.0) 11 (6, 19)
7 (1, 15) 53 (34, 86)
34 (3, 70)
*Estimated using 2018 census estimate for children <18 years 20

       SSSSiinininnuuuussssiiiittttiiiis ss s pneumococcal  an d vaccine  serotype
attributable  percents
Sinusitis attributable percent (95% CI)
Method All pneumococcal
serotypes PCV15-13 serotypes PCV20-13 serotypes
Vaccine probe 30.6 (21.0, 45.8) 1.5 (0.9, 2.5) 7.3 (4.9, 11.2)
Differential NP carriage 11.8 (1.0, 22.7) 0.6 (0.0, 1.2) 2.8 (0.2, 5.5)
21

        ss sii inn nuu uss sii itt tii iss s Estimated sinusitis pediatric outpatient visits and
antibiotic prescriptions attributable to PCV15-13
and PCV20-13 serotypes
Incidence per 1000 person-years Annual number in thousands*
(95% CI) (95% CI)
PCV15-13 PCV20-13 PCV15-13 PCV20-13
Outcome Method serotypes serotypes serotypes serotypes
Vaccine probe 0.6 (0.3, 1.2) 2.9 (1.7, 5.2) 44 (23, 85) 216 (122, 381)
Outpatient visits
Differential NP 0.2 (0.0, 0.5) 1.1 (0.1, 2.5) 17 (1, 40) 82 (7, 180) carriage
Vaccine probe 0.6 (0.3, 1.2) 2.9 (1.5, 5.2) 43 (21, 85) 209 (112, 384)
Antibiotic
prescriptions Differential NP 0.2 (0.0, 0.5) 1.1 (0.1, 2.5) 16 (1, 39) 79 (7, 181) carriage
22
*Estimated using 2018 census estimate for children <18 years
        SS Suu umm mmm maa arr ryy yaa ann ndd dcc coo onn ncc cll luu uss sii ioo onn nss s Summary and conclusions
23

              Point estimate ranges: attributable percent,
number visits, number antibiotic prescriptions
PCV15-13 serotypes PCV20-13 serotypes
Condition Attributable
percent of
outpatient
disease Annual no., in thousands
Outpatient Antibiotic
visits prescriptions Attributable
percent of
outpatient
disease Annual no., in thousands
Outpatient Antibiotic
visits prescriptions
AOM 0.7–1.0 76–109 65–93 3.7–5.1 397–543 340–464
Pneumonia 0.6–0.9 9–14 7–11 2.8–4.4 43–68 34-53
Sinusitis 0.6–1.5 17–44 16–43 2.8–7.3 82–216 79–209
Total* 1.9–3.4 103–168 90–148 9.4–16.8 527–831 458–731
*Individual condition ranges may not sum to total ranges due to simulation methods and rounding 24

 Study limitations
• Pneumococcal attributable percent, serotype distribution, and
vaccine effectiveness estimates based on published data
• Limited data for attributable proportion and serotype distribution in sinusitis and pneumonia
• All-cause incidence data from 2016-2018
• Assumed healthcare utilization constant across serotypes
25

 Conclusions
• Additional serotypes included in higher-valency PCVs account for
~100–830 thousand outpatient visits and ~90–730 thousand antibiotic prescriptions for AOM, pneumonia, and sinusitis among US children annually.
• PCV15-13 serotypes: 103–168K visits and 90–148K antibiotic prescriptions
• PCV20-13 serotypes: 527–831K visits and 458–731K antibiotic prescriptions
• The estimated incidence of pediatric outpatient visits and antibiotic prescriptions attributable to PCV20-13 serotypes is 4 – 5 times the
incidence attributable to PCV15-13 serotypes.
26

 Project team
UC Berkeley
• Laura King, MPH
• Joe Lewnard, PhD
CDC Respiratory Diseases Branch
• Miwako Kobayashi, MD, MPH
• Kristin Andrejko, PhD
• Adam Cohen, MD, MPH CDC Office of Antibiotic
Stewardship
• Sarah Kabbani, MD, MS
• Lauri Hicks, DO
27

Summary: Laur  a King,  MPH  Advisor  y Committ  ee o  n Immunizatio  n Practices  Februar  y 22  , 2023 PP PPeeeeddddiiiiaa aattttrrrriiiiccc    c oo oouu uuttttpp ppaaaattttii iiee eenn nnttt  t   AAAARR RRIII  I   vv vvii iissssii iitttts ss  s   aa aannnnddd  d   aa aannnnttttii iibbbbii iioo oott ttiiiic cc  c   uu uusssseee  e    aaaatt tttt ttrrrriiiibb bbuu uuttttaa aabb bblllleee    e tt tto oo  o   ss sseeeerrrroooott ttyyyypp ppeeees ss  s   ii iinnn  n   hhhhii iigg gghhhhee eerrr  r  …


Pneumococcal 04 Watson 508

20-valent Pneumococcal
Conjugate Vaccine
(PCV20) Phase 3
in Pediatrics
Wendy Watson, MD
Global Clinical Program Lead
ACIP February 22, 2023
1
PCV20 is Built on the Established Platforms of PCV7 and PCV13
• PCV20 builds on the 20 -year legacy of PCVs and contains PCV13 components + conjugates for 7 additional PCV20
Composition serotypes to broaden disease coverage for pneumococcal disease in children
• The 7 additional conjugates were modelled on the PCV13 Pfizer platform
• Licensure based on satisfactory safety and immunogenicity compared to PCV13
• Totality of data to support comparability per regulatory agreement Licensure and • Seeking same indications as PCV13 Indications
• PCV20 in the pediatric program is the same vaccine currently approved, recommended, and administered in
adults
PCV13 PCV20
PCV7
4 6B 9V 14 18C 19F 23F 1 3 5 6A 7F 19A 8 10A 11A 12F 15B 22F 33F

CRM197
PCV7
Immunogenicity  & Safety
Clinical Efficacy
Real -World Effectiveness
Real -World Impact
2 PCV13
Immunogenicity  & Safety
Efficacy from immunobridging
Real -World Effectiveness
Real -World Impact
Data available after vaccine implementation PCV20
Immunogenicity & Safety
Efficacy from Immunobridging
Real -World Effectiveness
Real -World Impact
Phase 2Senders
 et al. 2021 2, 4, 6 and
 12 months
 of age 460
Participants     Demonstrate safety, tolerability, and immunogenicity of PCV20
  •Concomitant administration with Pediarix
 •United States
Pivotal Infant
Study 2, 4, 6 and
 12–15 months
of age 1997
Participants  Demonstrate noninferiority of immune response of PCV20 vs PCV13
  •Concomitant administration with Pediarix , Hiberix , M-M-R II, Varivax
  •United States, Puerto RicoPhase 3 Pediatric
Single Dose
Study  Single dose
 (15 months –
<18 years
of age) 831
Participants       Characterize safety and immunogenicity in children 15 months to
17 years of age
 •United States
 Safety
Study  2, 4, 6 and
 12–15 months
of age 1511
Participants   Further characterize safety profile of PCV20
•Concomitant standard vaccines allowed
    •United States, Puerto Rico, Canada, Chile, Argentina, European UnionPCV20 Clinical Development Program
 SAFETY
IMMUNOGENICITY
3

  PCV20
N*=1001PCV13
N*=987
Sex n†(%) n†(%)
Male 518 (51.7) 505 (51.2)
Race
White 754 (75.3) 742 (75.2)
Black or African
American110 (11.0) 108 (10.9)
Asian 16 (1.6) 16 (1.6)
American Indian or
Alaska Native4 (0.4) 3 (0.3)
Native Hawaiian or
other Pacific
Islander2 (0.2) 2 (0.2)
Multiracial 68 (6.8) 73 (7.4)
Ethnicity
Hispanic/Latino 312 (31.2) 293 (29.7)
Non Hispanic/
nonLatino661 (66.0) 659 (66.8)-
-
Pivotal Infant  Study
Study Design of Phase 3 Pivotal Study in Infants
Multicenter, Randomized, Double -blind Study in the Similar Demographics of PCV20
US/Puerto Rico Study in Infants (92 sites, n=1997) and PCV13 Groups
2 4 6 7 12-15 13- 16 18- 21 Age months months months  months  months months months PCV20 PCV13
N*=1001 N*=987
Sex n† (%) n† (%)PCV20 Group
Male 518 (51.7) 505 (51.2)
Race
White 754 (75.3) 742 (75.2)+ + + + PCV20 PCV20
 PCV20 PCV20
Pediarix, Pediarix, Pediarix, MMR and
Hib Hib Hib Varicella
Control Group
+ + + + PCV13 PCV13 PCV13 PCV13
Black or African
American 110 (11.0) 108 (10.9)
Asian 16 (1.6) 16 (1.6)
American Indian or
Alaska Native 4 (0.4) 3 (0.3)
Native Hawaiian or
other Pacific 2 (0.2) 2 (0.2)
Islander
Multiracial 68 (6.8) 73 (7.4)
Ethnicity
Hispanic/Latino 312 (31.2) 293 (29.7)
Non-Hispanic/
non-Latino 661 (66.0) 659 (66.8) Pediarix,
Hib Pediarix,
Hib Pediarix,
Hib MMR and
Varicella
Blood draws Safety follow -up call • Concomitant Influen
any time during trial za and rotavirus vaccines permitted at
*N=number of participants in the specified age cohort. This value is the denominator for the percentage calculations.
†n=number of participants with the specified characteristic.
4
 Primary
Objectives

 Key
Secondary
Objective  Pre-specified Immunogenicity  Analyses
Importance of Multiple Immunologic Assessments to Infer Effectiveness Pivotal Infant Study
Co-primary :  Noninferiority  of  IgG GMCs  after
toddler dose Noninferiority  of  IgG GMC  after infant  series Co-primary  Noninferiority  of  % of  participants  with
IgG above predefined levels after infant series
Circulating IgG Antibody Functional Response Memory Response
• % above prespecified IgG level after
toddler dose • OPA GMTs after infant series and
toddler dose • Geometric fold -rises (GMFR) of IgG
from after infant series to after the
• IgG GMCs and % above prespecified
IgG for the 7 additional serotypes
relative to the PCV13 group •
• % with OPA titers ≥ LLOQ after infant
series and toddler dose
OPA titer RCDC after infant series and • toddler dose
GMFR of IgG from before to after the
toddler dose
• IgG Reverse Cumulative Distribution
Curve ( RCDC ) after infant series and
toddler dose toddler dose •
• GMFR of OPA from after infant series to
after the toddler dose
% with ≤ 4-fold rise in OPA titers from
before to after the toddler dose Additional Data
• Concomitant Vaccine Antigen GMCs
and GMRs
• Comparison of % With Prespecified
Antibody Levels for Concomitant
Vaccine Antigens
• Explore cross protection to 6C and 15C
NI for GMC ratio (GMR) = the lower bound of 2 -sided 95% CI for GMR (PCV20/PCV13) >0.5.
NI for difference in percentages of participants = the lower bound of 2 -sided 95% CI for percent difference (PCV20 -PCV13) > -10%.
5

         Pivotal Infant  Study Co-Primary  Objective
Post Dose 3 : Percentage with Predefined IgG Concentrations
14 Serotypes Met Noninferiority (Difference in %)
Serotype
PCV13 PCV20
(%) PCV13
(%) Difference (% )
(95% CI)
1 79.8 88.4 -8.6 (-12.1, -5.1)
3 52.1 67.6 -15.5 ( -20.1, -10.8)
4 79.7 88.2 -8.4 (-12.0, -4.9)
5 82.5 86.8 -4.3 (-7.8, -0.8)
6A 93.5 95.9 -2.4 (-4.6, -0.2)
6B 88.3 92.4 -4.1 (-7.0, -1.2)
7F 96.6 97.6 -1.0 (-2.7, 0.7)
9V 81.9 89.8 -7.9 (-11.3, -4.6)
14 93.4 94.1 -0.8 (-3.1, 1.6)
18C 92.6 93.1 -0.6 (-3.1, 1.9)
19A 97.1 98.1 -1.0 (-2.6, 0.5)
19F 96.9 96.6 0.2 (-1.5, 2.0)
23F 77.9 85.5* -7.6 (-11.4, -3.9)
7 Addition al
8 96.8 85.5 11.2 (8.6, 14.0)
10A 82.2 85.5 -3.3 (-6.9, 0.3)
11A 92.7 85.5 7.1 (4.2, 10.2)
12F 67.5 85.5 -18.1 ( -22.1, -14.0)
15B 98.2 85.5 12.7 (10.2, 15.4)
22F 98.3 85.5 12.8 (10.3, 15.5)
33F 86.7 85.5 1.1 (-2.2, 4.5)
-30 -20 -10 0 10 20 30
Difference in Percentage (PCV20 –PCV13)
*The 7 additional serotypes are compared to the percentage for serotype 23F after Dose 3 (lowest in PCV13 group, excluding serotype 3).
Predefined IgG concentration – ≥0.35 µg/mL for all serotypes except ≥ 0.23 µg/mL, ≥0.10 µg/mL and ≥ 0.12 µg/mL for serotypes 5, 6B and 19A respectively.
6

        Pivotal Infant Study Key Secondary   Objective
Post Dose 3 : IgG Concentration and Geometric Mean Ratio
All 20 Vaccine Serotypes Met Noninferiority
Serotype
PCV13 PCV20
GMC PCV13
GMC GMR
(95% CI)
1 0.74 1.14 0.65 (0.59, 0.72)
3 0.36 0.51 0.70 (0.64, 0.76)
4 0.75 1.08 0.70 (0.63, 0.78)
5 0.66 0.96 0.69 (0.61, 0.77)
6A 1.95 2.69 0.72 (0.65, 0.81)
6B 0.61 1.02 0.60 (0.51, 0.70)
7F 1.71 2.29 0.75 (0.69, 0.81)
9V 0.87 1.21 0.72 (0.65, 0.80)
14 2.16 2.72 0.79 (0.71, 0.89)
18C 1.31 1.71 0.77 (0.70, 0.84)
19A 0.72 0.91* 0.79 (0.72, 0.86)
19F 1.59 2.00 0.79 (0.73, 0.86)
23F 0.82 1.25 0.66 (0.58, 0.75)
7 Additional
8 1.80 0.91 1.98 (1.81, 2.16)
10A 1.21 0.91 1.32 (1.18, 1.49)
11A 1.39 0.91 1.52 (1.39, 1.67)
12F 0.55 0.91 0.60 (0.54, 0.67)
15B 4.40 0.91 4.82 (4.39, 5.30)
22F 3.71 0.91 4.06 (3.68, 4.48)
33F 1.49 0.91 1.64 (1.46, 1.83)
0.25 0.5 1 2 4 8
GMR
* The 7 additional serotypes are compared to the GMC after Dose 3 for serotype 19A (lowest in PCV13 group, excluding serotype 3).
7

   Pivotal Infant  Study
Post Dose 3 : IgG Concentration and Geometric Mean Ratio
Statistically Significantly Higher Response when compared to actual PCV13 Response
Comparison of additional 7 serotypes to actual PCV13 IgG GMC, not lowest in PCV20 group
Serotype
7 Additional PCV20
GMC PCV13
GMC GMR
(95% CI)
8 1.80 0.02 100.54 (91.58, 110.38)
10A 1.21 0.01 99.64 (88.87, 111.70)
11A 1.39 0.02 91.03 (82.79, 100.09)
12F 0.55 0.01 68.42 (62.47, 74.94)
15B 4.40 0.03 169.40 (154.01, 186.33)
22F 3.71 0.01 730.84 (651.36, 820.01)
33F 1.49 0.02 97.45 (86.96, 109.21)
0.25 0.5 1 2 4 8 16 32 64 128 256 512 1024
GMR
8
      Pivotal Infant  Study
Post Dose 3: Comparison of PCV20 and PCV13 OPA GMTs
Functional Antibody Responses Were Similar Between PCV20 and PCV13 for
Shared Serotypes
Post Dose 3
1 10 100 1000 10000
1 3 4 5 6A 6B 7F 9V 14 18C 19A 19F 23F 8 10A 11A 12F 15B 22F 33F OPA GMTs PCV20 PCV13
PCV20 (n= 80 –105); PCV13 (n=77 –113).
9

             Pivotal Infant Study Co-Primary  Objective
Post Dose 4 : IgG Concentration and Geometric Mean Ratio
All 20 Vaccine Serotypes Met Noninferiority
Serotype
PCV13 PCV20
GMC PCV13
GMC GMR Ratio
(95% CI)
1 1.47 2.12* 0.69 (0.63, 0.76)
3 0.56 0.85 0.66 (0.61, 0.73)
4 3.77 4.84 0.78 (0.70, 0.86)
5 1.87 2.51 0.74 (0.67, 0.82)
6A 9.01 11.69 0.77 (0.70, 0.85)
6B 4.01 5.74 0.70 (0.62, 0.79)
7F 3.91 5.18 0.76 (0.70, 0.82)
9V 3.44 4.30 0.80 (0.73, 0.88)
14 5.68 6.34 0.90 (0.81, 1.00)
18C 3.46 4.69 0.74 (0.67, 0.82)
19A 3.53 4.13 0.85 (0.77, 0.94)
19F 5.01 5.79 0.86 (0.78, 0.96)
23F 3.95 6.18 0.64 (0.57, 0.72)
7 Additional
8 3.97 2.12 1.87 (1.71, 2.06)
10A 6.22 2.12 2.94 (2.64, 3.26)
11A 3.53 2.12 1.67 (1.51, 1.84)
12F 1.85 2.12 0.88 (0.79, 0.97)
15B 12.59 2.12 5.95 (5.39, 6.55)
22F 10.60 2.12 5.01 (4.54, 5.52)
33F 9.31 2.12 4.40 (3.99, 4.85)
0.25 0.5 1 2 4 8
GMR
* The 7 additional serotypes were compared to serotype 1 in the PCV13 group (lowest IgG GMC after Dose 4, excluding serotype 3).
10

     Pivotal Infant Study
PD3 Compared to PD4: IgG and OPA Response to PCV20
Boosting Observed Across All 20 Serotypes Indicating Anamnestic Response/Memory
11 Post Dose 3 and Post Dose 4 IgG GMCs
Post Dose 3 and Pose Dose 4 O PA GMTs 0.01 0.1 1 10 100
1 3 4 5 6A 6B 7F 9V 14 18C 19A 19F 23F 8 10A 11A 12F 15B 22F 33F IgG GMCs PCV20 PD3 PCV20 PD4
1 10 100 1000 10000 100000
1 3 4 5 6A 6B 7F 9V 14 18C 19A 19F 23F 8 10A 11A 12F 15B 22F 33F OPA GMTs PCV20 PD3 PCV20 PD4
Pivotal Infant  Study
Concomitant Use : Responses to the Vaccines Were Similar When Given
with PCV20 or PCV13 in the Infant Immunization Series
All Responses Met Noninferiority
Post Dose 3: Pediarix and Hiberix®
Concomitant
Vaccine Antigen PCV20
(%) PCV13
(%) Difference (%)
(95% CI)
Diphtheria 93.5 97.8 -4.3 (-7.5, -1.4)
Tetanus 99.7 99.4 0.3 (- 1.0, 1.7)
Pertussis
PT 94.9 95.0 -0.2 (-3.5, 3.1)
FHA 95.7 95.0 0.6 (-2.5, 3.9)
PRN 93.8 95.0 -1.3 (-4.7, 2.2)
HBsAg 100.0 100.0 0.0 (-3.2, 2.9)
Poliovirus
Type 1 100.0 100.0 0.0 (- 3.4, 3.2)
Type 2 100.0 99.2 0.8 (- 2.4, 4.6)
Type 3 100.0 100.0 0.0 (- 3.2, 3.1)
Hib 100.0 100.0 0.0 (- 3.0, 3.0)
-15.0 -5.0 0.0 5.0 15.0
% Difference (PCV20 –PCV13)

 Post Dose 4: MMR ®II and Varivax®
Antigen
(Units) PCV20
GM PCV13
GM GMR
(95% CI)
277.74
36.96
49.63
233.05
0.25 0.50 1.00 2.00
GMR (PCV20:PCV13)

 Measles 215.41 1.29 (1.05, 1.58) (AU/mL)
Mumps 34.19 1.08 (0.85, 1.38) (AU/mL)
Rubella 40.44 1.23 (1.02, 1.48) (IU/mL)
Varicella 234.78 0.99 (0.84, 1.17) (mIU/mL)
         HBsAg = hepatitis B surface antigen; PT = pertussis toxoid, FHA =filamentous hemagglutinin (of Bordetella pertussis ), PRN = pertactin (of Bordetella pertussis )
12

 Pivotal Infant  Study
Solicited Reactions within 7 Days of Vaccination
Reactions Were Similar in Rate and Severity Across All 4 Doses
Local Reactions
100
80
60
%
40
25.5 24.6 26.4 25.4 27.2 26.6 23.2 23.5
16.4 18.8 15.5 17.3 17.1 17.6 14.9 17.3 49.1 45.3 44.1 41.7 38.6 39.0 35.7 35.8
Dose 1 Dose 2 Dose 3 Dose 4 Dose 1 Dose 2 Dose 3 Dose 4 Dose 1 Dose 2 Dose 3 Dose 4 Redness Swelling Injection Site Pain
PCV20 PCV13
Severe
20 Moderate
Mild
0
Systemic Reactions
100
Fever Decreased Appetite Drowsiness Irritability
80 70.9 71.7 71.6 68.8 67.2 66.0 64.4 63.0 61.1 61.0
60
%
10.3 7.5 17.3 16.3 12.6 13.7 14.5 14.0 24.4 23.9 26.4 23.5 20.6 22.4 24.8 25.2 54.7 55.6
44.1 44.1 39.5 39.5 PCV20 PCV13
>40.0 °C
Severe >38.9 –40.0°C
20 40
Moderate >38.4 –38.9°C
Mild ≥38.0 –38.4°C
0
Dose 1 Dose 2 Dose 3 Dose 4 Dose 1 Dose 2 Dose 3 Dose 4 Dose 1 Dose 2 Dose 3 Dose 4 Dose 1 Dose 2 Dose 3 Dose 4
PCV20: Dose 1=993, Dose 2=940, Dose 3=914, Dose 4=826. PCV13: Dose 1=974, Dose 2=924, Dose 3=901, Dose 4 =814.
13

    1523 mos
N†=2092 4 yrs
N†=2165 9 yrs
N†=2011017 yrs
N†=216
Sex n‡(%) n‡(%) n‡(%) n‡(%)
Male 117 (56.0) 106 (49.1) 108 (53.7) 115 (56.1)
Race
White 168 (80.4) 173 (80.1) 174 (86.6) 178 (86.8)
Black or African
American26 (12.4) 26 (12.0) 22 (10.9) 17 (8.3)
Asian 3 (1.4) 0 0 0
American Indian or Alaska Native0 1 (0.5) 0 0
Native Hawaiian or
other Pacific Islander0 0 0 1 (0.5)
Multiracial 10 (4.8) 13 (6.0) 5 (2.5) 9 (4.4)
Ethnicity
Hispanic/Latino 35 (16.7) 45 (20.8) 31 (15.4) 43 (21.0)
Non Hispanic/Latino 172 (82.3) 171 (79.2) 168 (83.6) 161 (78.5)– – – –
-Demographic Characteristics –
Safety Population
15–23 mos 2 –4 yrs 5 –9 yrs 10–17 yrs
N†=209 N†=216 N†=201 N†=216
Sex n‡ (%) n‡ (%) n‡ (%) n‡ (%)
Male 117 (56.0) 106 (49.1) 108 (53.7) 115 (56.1)
Race
White 168 (80.4) 173 (80.1) 174 (86.6) 178 (86.8)
Black or African
American 26 (12.4) 26 (12.0) 22 (10.9) 17 (8.3)
Asian 3 (1.4) 0 0 0
American Indian or Alaska Native 0 1 (0.5) 0 0
Native Hawaiian or
other Pacific Islander 0 0 0 1 (0.5)
Multiracial 10 (4.8) 13 (6.0) 5 (2.5) 9 (4.4)
Ethnicity
Hispanic/Latino 35 (16.7) 45 (20.8) 31 (15.4) 43 (21.0)
Non-Hispanic/Latino 172 (82.3) 171 (79.2) 168 (83.6) 161 (78.5)

       Phase 3 Study
Age Prior
Group Vaccination Status Day 1 1 month 6 months
PCV20 Group
         Pediatric Single Dose Study Design and Demographics Single Dose Study
PCV20
 ≥3 doses of PCV13
15–23
months*
2–4
years*
5–9
years
10–17
years
Blood draws PCV20
 ≥3 doses of PCV13
PCV20
 Not required
PCV20
 Not required
Safety follow -up call
*Participants <5 years of age had confirmed receipt of >3 prior doses of PCV13.
† N=number of participants in the specified age cohort. This value is the denominator for the percentage calculations. ‡ n=nu mber of participants with the specified characteristic.
14

 IgG GMC in Children Previously Vaccinated with PCV13
One Dose of PCV20 Elicited Responses to All Vaccine Serotypes Single Dose Study
15 15 to <24 Months
2 to <5 Years 0.01 0.1 1 10 100
1 3 4 5 6A 6B 7F 9V 14 18C 19A 19F 23F 8 10A 11A 12F 15B 22F 33F IgG GMCs
Before PCV20 1 Month After PCV20
0.01 0.1 1 10 100
1 3 4 5 6A 6B 7F 9V 14 18C 19A 19F 23F 8 10A 11A 12F 15B 22F 33F IgG GMCs
Before PCV20 1 Month After PCV20
Overall  Safety
Overall Summary of Adverse Events in the US
PCV20 had no Related Serious Adverse Events or Deaths
Age < 15 months
16 *SAEs reported  are  in all  sites,  not  just  US (including  Puerto  Rico).
B7471003, B7471011,  and  B7471013 (all  sites) : (PCV20 N=2232;  PCV13 N=1717)

 15 m -<18 yr
PCV20
(N=1567) PCV13
(N=1376) PCV20
(N=831)
AEs 43.8% 46.3% 10.7%
 Immediate AEs 0.1–0.2% /dose 0.1% /dose 0%
 Related AE 1.1% 1.1% 0.1%
 Severe AEs 1.4% 1.1% 0.2%
Serious AEs* 4.5%* 3.7%* 0.6%
 Related SAEs 0 0 0
Deaths 0 0 0

    Summary of PCV20 Pediatric
PCV20 is well tolerated with a safety profile similar to PCV13
The totality of data shows PCV20 elicits immune responses to all 20 vaccine serotypes
A single dose of PCV20 elicited a robust immune response to all 20 serotypes and was well tolerated in
children 15 months to < 18 years of age, including those with prior PCV13
PCV20 is compatible with routine pediatric vaccines
PCV20 is currently under review by the FDA for use in pediatric population 6 weeks to <18 years of age
with a target action date in April 2023
PCV20 has the potential to address a substantial burden of pneumococcal disease in children
17
Questions?
18

Summary: 20-valent Pneumococcal  Conjugate Vaccine  (PCV20) Phase 3  in Pediatrics  Wendy Watson, MD  Global Clinical Program Lead  ACIP February 22, 2023  1  PCV20 is Built on the Established Platforms of PCV7 and PCV13  • PCV20 builds on the 20 -year legacy of PCVs and contains PCV13 components + conjugates for 7 additional PCV20  Composition serotypes to broaden disease coverage for pneumococcal disease in children  • The 7 additional conjugates were modelled on the PCV13 Pfizer platform  •…