06 Pneumococcal Kobayashi 508

Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
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Preliminary Work Group Interpretations of EtR  and
Next Steps
February 2024, ACIP Meeting
February 29, 2024
Miwako Kobayashi, MD, MPH, FACP , FIDSA
1.Should PCV21 be recommended for U.S. adults aged ≥19 years who
currently have a recommendation to receive a PCV*?
Comparison (current recommendations):
Adults aged ≥19 years  who have not received a PCV
One dose of PCV15 followed by PPSV23
One dose of PCV20
Adults aged ≥19 years who have received a PCV but have not completed the recommended series
One dose of PCV20
≥1 dose of PPSV23Policy Questions Being Considered by the Work Group
*Includes,
• Adults aged ≥65 years who have never received a PCV
• U.S. adults aged 19-64 years with a risk condition, who have never received a PCV
• U.S. adults aged ≥19 year who have received a PCV (i.e., PCV7, PCV13, or PCV15), but have not completed the recommended series
2. Should PCV21 be recommended for U.S. adults aged 50- 64 years who
currently do not have a risk -based pneumococcal vaccine indication?
3. Should PCV21 be recommended for U.S. adults aged 19 -49 years who
currently do not have a risk -based pneumococcal vaccine indication?
Comparison (current recommendation):
No vaccine
Questions 2 and 3 imply a new age -based recommendation for these age groups.Policy Questions Being Considered by the Work Group
EtR  Domain Question
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?
•What is the overall certainty of this evidence for the critical outcomes?
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 outcomes?
Acceptability •Is the intervention acceptable to key stakeholders?
Feasibility •Is the intervention feasible to implement?
Resource Use •Is the intervention a reasonable and efficient allocation of resources?
Equity •What would be the impact of the intervention on health equity?Evidence to Recommendations ( EtR ) framework
4
EtR  Domain Question
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?
•What is the overall certainty of this evidence for the critical outcomes?
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 outcomes?
Acceptability •Is the intervention acceptable to key stakeholders?
Feasibility •Is the intervention feasible to implement?
Resource Use •Is the intervention a reasonable and efficient allocation of resources?
Equity•What would be the impact of the intervention on health equity?Evidence to Recommendations ( EtR ) framework
5
EtR  Public Health Problem
Is pneumococcal disease of public health importance?
Prior to the COVID-19 pandemic, estimated to have caused
every year1:
–≥100,000 non- invasive pneumococcal pneumonia hospitalizations
–≥30,000 invasive pneumococcal disease (IPD) cases (e.g., bacteremic pneumonia,
pneumococcal bacteremia, meningitis)
•3,000 IPD deaths
Risk of disease and severe outcomes is higher among older adults and adults with certain risk conditions.
–Over one -third of adults aged ≥65 years hospitalized with community -acquired
pneumonia in Louisville, KY died within 1 year2
–>80% of IPD cases occurred among adults with risk -based indications3Pneumococcal Disease Burden among U.S. Adults
1. Kobayashi M. October 20, 2021 ACIP Meeting Presentation. Considerations for Age -Based and Risk -Based Use of PCV15 and PCV20 amon g U.S. Adults and Proposed Policy Options.
2. Older Adults Hospitalized for Pneumonia in the United States: Incidence, Epidemiology, and Outcomes - Arnold - 2020 - Journal of  the American Geriatrics Society - Wiley Online Library
3. CDC Active Bacterial Core surveillance unpublished data
IPD incidence reached a historically low level early in the COVID -19
pandemic, but increasing toward pre- COVID levels
IPD=invasive pneumococcal disease; 2022 data in gray are preliminary
ABCs Bact  Facts Interactive Data Dashboard | CDC

New pneumococcal conjugate vaccines, PCV15 and PCV20,
were recommended for adults and children in recent years
2021 2023 2022
PCV15 : ChildrenPCV20 : Expanded
indication for adults
who previously
received PCV13
PCV20 : ChildrenPCV15 and PCV20:  Adults
who have not received
PCV or whose vaccination history is unknown
30–40% of adult IPD cases* are caused by serotypes not
contained in currently available vaccines; PCV21 contains
most  of them.
*Based on ABCs 2018 –2022 data421615216
0102030405060708090100Percent IPD
PCV15+6C PCV20/non-PCV15
PPV23/non-PCV20 PCV21/non-PPV23
NVT42129298
0102030405060708090100Percent IPD
PCV15+6C PCV20/ non-PCV15
PPV23/ non-PCV20 PCV21/ non-PPV23
NVTAged 19 –64 years, with a risk- based
indication Aged ≥65 years
1. In adults currently recommended to receive a PCV ? (group 1)Is pneumococcal disease of public health importance?
□ No
□ Probably no
□ Probably yes
□ Yes
□ Varies
□ Don’t know   Minority opinion (probably yes):
•Pneumococcal disease burden has decreased from
before
•Increase in disease incidence in recent years does not mean the incidence will continue to increase (i.e., may stabilize at pre -COVID -19 levels)
2. In adults aged 50– 64 years who currently do not have a risk -based
pneumococcal vaccine indication ? (group 2)Is pneumococcal disease of public health importance?
□ No
□ Probably no
□ Probably yes
□ Yes
□ Varies
□ Don’t know   •Disease incidence in this age group overall is lower
compared with adults aged ≥65 years (IPD incidence ~23% lower)
3. In adults aged 19 –49 years who currently do not have a risk -based
pneumococcal vaccine indication ? (group 3)Is pneumococcal disease of public health importance?
□ No
□ Probably no
□ Probably yes
□ Yes
□ Varies
□ Don’t know   •The most common WG member responses were
“No”(19%), “Probably No”(31%), and “Don’t know (25%)
•Adults aged 19 –49 years have even lower disease
incidence compared with adults aged 50 –64 years
EtR  Benefits and Harms
1. How substantial are the desirable  anticipated effects of PCV21 vaccination?
2. How substantial are the undesirable  anticipated effects of PCV21
vaccination?
3. Do the desirable effects of PCV21 vaccination outweigh the undesirable
effects?
4. What is the overall certainty of this evidence for the critical outcomes?
Outcomes (Benefits)
*Rated on a 1 to 9 scale, where 7 –9 are critical, 4 –6 are important, 1 –3 are of limited importance
GMT= geometric mean titers; OPA=opsonophagocytic activity
See supplementary slides for details of methodsOutcome Importance* Description
VT- IPD Critical
VT- non- bacteremic
pneumococcal pneumoniaCritical
VT- pneumococcal deaths Critical
All IPD Important
Non -bacteremic
pneumococcal pneumoniaImportant
All-cause death ImportantStudies assessing PCV21 against these
clinical outcomes are currently not
available
PCV21 immunogenicity studies
•OPA GMT
•≥4-fold rise in serotype -specific
OPA responses
Outcomes (Harms)
*Rated on a 1 to 9 scale, where 7 –9 are critical, 4 –6 are important, 1 –3 are of limited importance
See supplementary slides for details of methodsOutcome Importance* Description
Serious adverse events
(SAE)Critical Safety data for PCV21 are available.
Last name first
author, Publication
yearStudy design Country Age Total population N Intervention N comparison OutcomesFunding
source
Platt, Lancet ID
2023RCT (Phase II) U.S. Adults ≥50 years 508 254 PPSV23: 254Immunogenicity and
SafetyMERCK
V116 -003RCT (Phase III);
pivotal studyU.S., Australia, Belgium,
Chile, Germany, Korea,
New Zealand, Puerto
Rico, Sweden, Taiwan,
TurkeyHealthy adults ≥50 years,
pneumococcal vaccine –
naïve2,6631179 PCV20: 1,177
Immunogenicity and
SafetyMERCKHealthy adults 18 - 49 years,
pneumococcal vaccine –
naïve200 PCV20:  100
V116 -005RCT (Phase III)U.S. Adults ≥50 years 1,080(V116 + QIV,
coadministered): 536(QIV followed by
V116) : 536Immunogenicity and
SafetyMERCK
V116 -006RCT (Phase III)U.S., Canada, Israel,
France, Italy, Japan,
Korea, Spain, TaiwanAdults ≥50 years, previous
PPSV23 ≥1 year prior to
enrollment348 229PCV15, n=119
Immunogenicity
and
SafetyMERCKAdults ≥50 years, previous
PCV13 ≥1 year prior to
enrollment259 174PPSV23
N=85
Adults ≥50 years,
PCV13+PPSV23,
PCV15+PPSV23, PCV15,
PCV20, or PPSV23+PCV13 ≥1
year prior to enrollment105 105 None
V116 -007 RCT (Phase III)Belgium,  Chile,  France,
South Africa,
Thailand,
United StatesAdults living with HIV,
≥18 years; 36% prior PCV13
or PPSV23*313 156PCV15+PPSV23,
n=157Immunogenicity and
SafetyMERCK
V116 -004RCT (Phase III)U.S., Austria, Canada,
Denmark, Finland, Israel,
Poland, SpainAdults 18 - 49 years with
underlying chronic
conditions2,162 1,617 PPSV23:540 SafetyMERCKPCV21 Clinical Trials Included in Evidence Review
Certainty assessment № of patients Effect
Certainty Importance№ of
studiesStudy designRisk of
biasInconsistency Indirectness ImprecisionOther
considerationsPCV21 comparisonRelative
(95% CI)Absolute
(95% CI)
VT-IPD, VT -nonbacteremic pneumococcal pneumonia, VT -pneumococcal mortality outcome (Assessed with: Immunogenicity)
51-5Randomized
studiesNot
seriousNot serious SeriousaNot serious Not serious 123 - 1161 58 - 1162• PCV21 met non -inferiority criteriab
for 9/9 shared and superiority
criteriac for 12/12 unique serotypes
vs. PPSV23
• PCV21 met non -inferiority criteriad
for 10/10 shared and superiority
criteriae 10/11 unique serotypes vs.
PCV20
• PCV21 had numerically higher
immune responses for 1 -4/6 shared
and all unique serotypes vs. PCV15Moderate CriticalGRADE Summary of Findings Table
1: Adults currently recommended to receive PCV
a. These are all immunogenicity studies and there are no correlates of protection for some critical outcomes considered.
b. Noninferiority for GMT ratio was defined as the lower bound of the 95% CI of the estimated OPA GMT ratio ({PCV21:PPSV23} to be >  0.33.
c. Superiority for GMT ratio was defined as the lower bound of the 95% CI of the estimated OPA GMT ratio [PCV21:PPSV23] to be > 1.0.
d. Noninferiority for GMT ratio was defined as the lower bound of the 2 sided 95% CI of the OPA GMT ratio [PCV21 / PCV20] to be >0.5.
e. Superiority for GMT ratio was defined as the lower bound of the 2 sided 95% CI of the OPA GMT ratio [PCV21 / PCV20] to be >2. 0.
References
1. Platt H, Omole T, Cardona J, Fraser NJ, Mularski  RA, Andrews C, Daboul  N, Gallagher N, Sapre A, Li J, Polis A, Fernsler  D, Tamms G, Xu W, Murphy R, Skinner J, Joyce J, Musey L. Safety, tolerability, and immunogenicity of a 21- valent pneumococcal c onjugate vaccine,
V116, in healthy adults: phase 1/2, randomised, double- blind, active comparator -controlled, multicentre, U.S.- based trial. Lancet Infect Dis. 2023 Feb;23(2):233- 246. doi: 10.1016/S1473- 3099(22)00526 -6. Epub 2022 Sep 15. PMID: 36116461.
2. V116- 003. A clinical study to evaluate the safety, tolerability, and immunogenicity of V116 compared to PCV20 in pneumococcal vaccine -naïve adults
3. V116- 006. A Phase 3 Clinical Study to Evaluate the Safety, Tolerability, and Immunogenicity of V116 in Pneumococcal Vaccine- Experienced Adults 50 Years of Age or Older
4. V116- 007. A Phase 3, Multicenter, Randomized, Double- blind, Active Comparator - Controlled Study to Evaluate the Safety, Tolerabi lity, and Immunogenicity of V116 in Adults Living With HIV
5. V166- 005. A clinical study comparing the immunogenicity and safety of V116 when administered concomitantly with inactivated infl uenza vaccine
GRADE Summary of Findings Table
1: Adults currently recommended to receive PCV
a. These are all immunogenicity studies and there are no correlates of protection for some critical outcomes considered.
b. Noninferiority for GMT ratio was defined as the lower bound of the 95% CI of the estimated OPA GMT ratio ({PCV21:PPSV23} to be >  0.33.
c. Superiority for GMT ratio was defined as the lower bound of the 95% CI of the estimated OPA GMT ratio [PCV21:PPSV23] to be > 1.0.
d. Noninferiority for GMT ratio was defined as the lower bound of the 2 sided 95% CI of the OPA GMT ratio [PCV21 / PCV20] to be >0.5.
e. Superiority for GMT ratio was defined as the lower bound of the 2 sided 95% CI of the OPA GMT ratio [PCV21 / PCV20] to be >2. 0.
 See supplementary slides for details
Certainty assessment № of patients Effect
Certainty Importance№ of
studiesStudy designRisk of
biasInconsistency Indirectness ImprecisionOther
considerationsPCV21 comparisonRelative
(95% CI)Absolute
(95% CI)
Serious adverse events following immunization
61-6Randomized
studiesNot
seriousNot serious Not serious SeriousfNot serious 57/4445
(1.3%)63/2962
(2.1%)Absolute % difference for SAEs across
studies is -0.8%; two SAEs deemed
vaccine -relatedg in the V116 group
reportedModerate CriticalGRADE Summary of Findings Table
1: Adults currently recommended to receive PCV
f. few vaccine- related serious adverse events reported.
g. Bronchospasm (V116- 005): 50- year-old female in the sequential group with bronchospasm within 30 minutes after the 2ndvaccination (V116); duration 23 hours; resolved; Injection site cellulitis (V116- 006): 67- year-old female in Cohort 1 (prior PPSV23) with i njection site cellulitis
on Day 6; duration 1.57 weeks; resolved (Merck, unpublished).
References
1. Platt H, Omole T, Cardona J, Fraser NJ, Mularski  RA, Andrews C, Daboul  N, Gallagher N, Sapre A, Li J, Polis A, Fernsler  D, Tamms G, Xu W, Murphy R, Skinner J, Joyce J, Musey L. Safety, tolerability, and immunogenicity of a 21- valent pneumococcal c onjugate vaccine,
V116, in healthy adults: phase 1/2, randomised, double- blind, active comparator -controlled, multicentre, U.S.- based trial. Lancet Infect Dis. 2023 Feb;23(2):233- 246. doi: 10.1016/S1473- 3099(22)00526 -6. Epub 2022 Sep 15. PMID: 36116461.
2. V116- 003. A clinical study to evaluate the safety, tolerability, and immunogenicity of V116 compared to PCV20 in pneumococcal vaccine -naïve adults
3. V116- 006. A Phase 3 Clinical Study to Evaluate the Safety, Tolerability, and Immunogenicity of V116 in Pneumococcal Vaccine- Experienced Adults 50 Years of Age or Older
4. V116- 007. A Phase 3, Multicenter, Randomized, Double- blind, Active Comparator - Controlled Study to Evaluate the Safety, Tolerabi lity, and Immunogenicity of V116 in Adults Living With HIV
5. V166- 005. A clinical study comparing the immunogenicity and safety of V116 when administered concomitantly with inactivated infl uenza vaccine
6. V116- 004. A Phase 3 Randomized, Double- blind, Active Comparator -controlled, Lot to- Lot Consistency Study to Evaluate the Safety,  Tolerability, and Immunogenicity of V116 in Adults 18 to 49 Years of Age.
GRADE Summary of Findings Table
1: Adults currently recommended to receive PCV
f. few vaccine- related serious adverse events reported.
g. Bronchospasm (V116- 005): 50- year-old female in the sequential group with bronchospasm within 30 minutes after the 2ndvaccination (V116); duration 23 hours; resolved; Injection site cellulitis (V116- 006): 67- year-old female in Cohort 1 (prior PPSV23) with i njection site cellulitis
on Day 6; duration 1.57 weeks; resolved (Merck, unpublished).
See supplementary slides for details
1. How substantial are the desirable  anticipated effects of
PCV21 vaccination?
□ Minimal
□ Small
□ Moderate
□ Large
□ Varies
□ Don’t know   □ Minimal
□ Small
□ Moderate
□ Large
□ Varies
□ Don’t know   □ Minimal
□ Small
□ Moderate
□ Large
□ Varies
□ Don’t know   1. Adults currently
recommended to receive PCV2. Adults aged 50 –64 years with
no risk -based indication3. Adults aged 19 –49 years with
no risk -based indication
 1. Adults currently recommended to receive PCV
 2. Adults aged 50 –64 years with no risk- based indication
 3. Adults aged 19 –49 years with no risk- based indication2. How substantial are the un desirable  anticipated effects
of PCV21 vaccination?
□ Minimal
□ Small
□ Moderate
□ Large
□ Varies
□ Don’t know
□ Favors PCV21 use
□ Favors current
□ Favors both
□ Favors neither
□ Varies
□ Don’t know   3. Do the desirable effects of PCV21 vaccination outweigh
the undesirable  anticipated effects?
1. Adults currently
recommended to receive PCV2. Adults aged 50 –64 years with
no risk -based indication3. Adults aged 19 –49 years with
no risk -based indication
□ Favors PCV21 use
□ Favors current (no
vaccine)
□ Favors both
□ Favors neither
□ Varies
□ Don’t know   □ Favors PCV21 use
□ Favors current (no
vaccine) □ Favors both
□ Favors neither
□ Varies
□ Don’t know
•None selected by the majority
•“Favors current” and “favors PCV21
use” were the most common responses selected by similar number of members
Based on available data, no concerns about the risks outweighing the
benefits of PCV21 vaccination
For adults who currently have a PCV recommendation, PCV21 provides broader serotype coverage than currently recommended vaccinesSummary of Work Group Discussions:
Comments in favor of PCV21 use
We can expect a more robust immune response from administering
PCV21 at age 50 –64 years (vs. age ≥65 years) and before a portion of that
population develops an immunocompromising condition  Summary of Work Group Discussions:
In favor of lowering the age -based recommendation (question 2)
The degree of benefits for adults who currently don’t have vaccine
recommendations is uncertain
Epidemiology does not support expanding the vaccine indications to younger adults without a risk -based indication
Younger adults (early 20s) would have received a PCV as a child
We could miss the opportunity to provide protection against disease later in life if we lowered the age- based recommendation
–Limited data on duration of protection or protection against disease from multiple
PCV doses in adults
Need to review cost- effectiveness analysis dataSummary of Work Group Discussions:
Concerns/uncertainties of lowering the age- based recommendation
(especially question 3)
EtR : Equity
What would be the impact of recommending PCV21 use for adults on
health equity?
Racial disparities in IPD incidence exist
White non- Hispanic adults tend to have
highest vaccine coverage1 compared with
other race/ethnicity groups
Remaining disparities in IPD incidence are
primarily due to non- PCV13 -type  diseaseRacial disparities exist in IPD incidence and vaccine
coverage
Figure: ABCs unpublished data
1. Vaccination Coverage among Adults in the United States, National Health Interview Survey, 2021 | CDC

Adults experiencing homelessness (especially Western United States)
•100– 300 times higher serotype 4  IPD incidence reported in people experiencing
homelessness (PEH) vs. non -PEH in the Western United States1
Adults in Alaska (especially Alaska Native adults)
•88-fold increase in serotype 4 IPD incidence reported in adults in Alaska, 2011 –2018
vs. 2019– 20202 Increase in serotype 4  (included in currently available vaccines,
not in PCV21) IPD reported in certain subpopulations
1. Upsurge of Conjugate Vaccine Serotype 4 Invasive Pneumococcal Disease Clusters Among Adults Experiencing Homelessness in C alifornia, Colorado, and New Mexico | The
Journal of Infectious Diseases | Oxford Academic (oup.com)
2. Invasive Pneumococcal Disease and Potential Impact of Pneumococcal Conjugate Vaccines Among Adults, Including Persons Experie ncing Homelessness— Alaska, 2011 –2020 |
Clinical Infectious Diseases | Oxford Academic (oup.com)
1. In adults currently recommended to receive a PCV ?What would be the impact of recommending PCV21 use for
adults on health equity?
□ Reduced
□ Probably reduced
□ Probably no impact
□ Probably increased
□ Increased
□ Varies
□ Don’t know •Additional serotype coverage by PCV21 is expected
to reduce racial disparities in remaining
pneumococcal disease burden.
•For adults who have already received a PCV,
recommending a second PCV dose to complete
series might magnify the underlying disparities in
vaccine coverage.
2. In adults aged 50– 64 years who currently do not have a risk -based pneumococcal
vaccine indication ?
3. In adults aged 19 –49 years who currently do not have a risk -based pneumococcal
vaccine indication ?What would be the impact of recommending PCV21 use for
adults on health equity?
□ Reduced
□ Probably reduced
□ Probably no impact
□ Probably increased
□ Increased
□ Varies
□ Don’t know •Probably more equitable to lower the age threshold
for the age -based recommendation, which may
improve vaccine coverage in those who currently have risk -based indications
EtR Domains 1. Adults with current PCV
recommendations2. Adults aged 50– 64
years, no risk -based
indication3. Adults aged 19– 49
years, no risk -based
indication
Public Health Problem Yes Probably Yes No/Probably No
Benefits and Harms
a. Benefits Moderate/Large Small/Moderate Minimal/Small
b. Harms Minimal
c. Benefit>Harm? Favors PCV21 use Favors PCV21/Favors no
vaccine (split)
d. Overall certainty: effectiveness Moderate
e. Overall certainty: safety Moderate
Equity Probably increasedSummary of Work Group Interpretation of the EtR  Domains
Work Group Next Steps
Review findings from cost -effectiveness analyses
Review evidence and discuss interpretations of remaining EtR
domains (Values, Acceptability, Resource Use, Feasibility)
Draft policy options on PCV21 use in U.S. adults for
consideration by the committee
–Including considerations for expanding the current risk -based vaccine
indications to include adults with chronic kidney disease (CKD) who are not on
maintenance dialysisWork Group Next Steps
Considerations for including earlier stages of
CKD for risk -based pneumococcal vaccine
indications
Indications for risk -based pneumococcal vaccine recommendations Children Adults
Alcoholism
Chronic heart disease†
Chronic kidney disease (excluding maintenance dialysis and nephrotic syndrome)Chronic liver disease
Chronic lung disease
Cigarette smokingDiabetes mellitusCerebrospinal fluid leakCochlear implant
Maintenance dialysis or nephrotic syndrome
Congenital or acquired asplenia, or splenic dysfunctionCongenital or acquired immunodeficiency
¶
Diseases and conditions treated with immunosuppressive drugs or radiation therapy**HIV infectionSickle cell disease or other hemoglobinopathies
Solid organ transplantRisk -based pneumococcal vaccine indication was expanded to
include earlier -stage CKD (i.e., those not on dialysis) in children.
Does evidence support the change in adults as well?
In favor of expanding indications in
adults:
Pneumococcal disease risk is increased in earlier CKD stages
Allows adults to receive vaccine when immune response is more robust Concerned/cautious about expanding indications in adults
Unlike children, CKD is more common in adults
Inclusion of earlier stages, such as CKD stage 3a, could potentially result in expanding the risk- based indication to
a much larger proportion of adults (unless they already have other risk-based indications)
Would like to see a cost -benefit
analysis Summary of Work Group Discussion to Date
Considering:
Additional pneumococcal vaccines for adults are currently under investigation and
may be approved in the near future, and
Dynamic changes in pneumococcal disease incidence are anticipated post -COVID -19
and with increased uptake in PCV15/PCV20 in children and adults

1. Do you have any feedback on the policy questions being considered by the WG?2. What additional data would be helpful to inform the discussions on PCV21 use in
adults?
In addition,
3. What additional data would be needed to help inform the discussions on expanding
the risk- based indications to include adults with CKD?
 Questions for the Committee
ACIP and the Pneumococcal Vaccines Work Group
CDC contributors and consultants: Ryan Gierke, Jennifer Farrar, Kristin Andrejko,
Lindsay Zielinski, Emma Accorsi, Wei Xing, Adam Cohen, Alison Albert, Angela Jiles, Noele Nelson, Kimberly Fox, Pedro Moro, Elizabeth Velazquez, Janelle King, Fangjun Zhou, Marc Fischer, Cheryl Ward, Rebecca Morgan, Doug Campos -Outcalt
Active Bacterial Core surveillance sites and programAcknowledgments
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!
GRADE Evidence Summary
Supplemental Slides
PICO 1: Adults currently recommended to receive PCV
Policy question: Should PCV21 be recommended for U.S. adults aged ≥19 years who currently have a
recommendation to receive a pneumococcal conjugate vaccine?
Population •U.S. adults aged ≥65 years who have never received a PCV
•U.S. adults aged 19 –64 years with a risk condition, who have never received a PCV
•U.S. adults aged ≥19 years who have received a PCV (i.e., PCV7, PCV13, or PCV15), but
have not completed the recommended series
Intervention One dose of PCV21 (V116)
Comparison Adults who have not received a PCV
•One dose of PCV15 followed by PPSV23
•One dose of PCV20
Adults who have received a PCV but have not completed the recommended series
•One dose of PCV20
•≥1 dose of PPSV23
Outcomes Vaccine type (VT)-IPD, VT -non -bacteremic  pneumococcal , VT -pneumococcal mortality,
serious adverse events
PICO2: Adults aged 50–64 years, no risk- based indications
Policy question: Should PCV21 be recommended for U.S. adults aged 50 –64 years who currently
do not have a risk -based pneumococcal vaccine indication?
Population U.S. adults aged 50 –64 years who currently do not have a risk -based pneumococcal
vaccine indication
Intervention One dose of PCV21
Comparison No vaccination
Outcomes Vaccine type (VT) -IPD, VT -non- bacteremic pneumococcal , VT -pneumococcal
mortality, serious adverse events
PICO3: Adults aged 19–49 years, no risk- based indications
Policy question: Should PCV21 be recommended for U.S. adults aged 19 –49 years who currently
do not have a risk -based pneumococcal vaccine indication?
Population U.S. adults aged 19 –49 years who currently do not have a risk -based pneumococcal
vaccine indication
Intervention One dose of PCV21
Comparison No vaccination
Outcomes Vaccine type (VT) -IPD, VT -non- bacteremic pneumococcal , VT -pneumococcal
mortality, serious adverse events
Search strategy
Database StrategyNo.
identifiedIncluded in
GRADE
clinicaltrials
.govSearch terms (searched separately): "V116"; "21 -valent pneumococcal conjugate vaccine";"PCV21"
Inclusion: Relevant Phase 2 or 3 randomized controlled trials of PCV21
• Involved human subjects
• Reported primary data
• Included adults (age ≥19 years)
• Included data relevant to the efficacy or effectiveness or immunogenicity and safety outcomes
being measured
10 6
Pubmed "V116" or "21 -valent pneumococcal conjugate vaccine" or "PCV21"
Included studies using the criteria listed above25 1
Additional
resourcesUnpublished and other relevant data by consulting with vaccine manufacturers and subject matter experts
5
Evidence Retrieval
Clinicaltrials.gov
N=10
6 studies included for GRADEPubmed
N=25
PCV21 50 – 64y, no risk
based indication
Immunogenicity (n=2)
SAE (n=2)Unpublished data
N=5
PCV21 for currently
recommended adults
(n=6)
Immunogenicity (n=5)
SAE (n=6)PCV21 19 – 49y, no risk
based indication
Immunogenicity (n=1)
SAE (n=1)
Last name first
author, Publication
yearStudy design Country Age Total population N Intervention N comparison OutcomesFunding
source
Platt, Lancet ID
2023RCT (Phase II) U.S. Adults ≥50 years 508 254 PPSV23: 254Immunogenicity and
SafetyMERCK
V116 -003RCT (Phase III);
pivotal studyU.S., Australia, Belgium,
Chile, Germany, Korea,
New Zealand, Puerto
Rico, Sweden, Taiwan,
TurkeyHealthy adults ≥50 years,
pneumococcal vaccine –
naïve2,6631179 PCV20: 1,177
Immunogenicity and
SafetyMERCKHealthy adults 18 - 49 years,
pneumococcal vaccine –
naïve200 PCV20:  100
V116 -005RCT (Phase III)U.S. Adults ≥50 years 1,080(V116 + QIV,
coadministered): 536(QIV followed by
V116) : 536Immunogenicity and
SafetyMERCK
V116 -006RCT (Phase III)U.S., Canada, Israel,
France, Italy, Japan,
Korea, Spain, TaiwanAdults ≥50 years, previous
PPSV23 ≥1 year prior to
enrollment348 229PCV15, n=119
Immunogenicity
and
SafetyMERCKAdults ≥50 years, previous
PCV13 ≥1 year prior to
enrollment259 174PPSV23
N=85
Adults ≥50 years,
PCV13+PPSV23,
PCV15+PPSV23, PCV15,
PCV20, or PPSV23+PCV13 ≥1
year prior to enrollment105 105 None
V116 -007 RCT (Phase III)Belgium,  Chile,  France,
South Africa,
Thailand,
United StatesAdults living with HIV,
≥18 years; 36% prior PCV13
or PPSV23*313 156PCV15+PPSV23,
n=157Immunogenicity and
SafetyMERCK
V116 -004RCT (Phase III)U.S., Austria, Canada,
Denmark, Finland, Israel,
Poland, SpainAdults 18 - 49 years with
underlying chronic
conditions2,162 1,617 PPSV23:540 SafetyMERCKPCV21 Clinical Trials included in Evidence Review
Certainty assessment № of patients Effect
Certainty Importance№ of
studiesStudy designRisk of
biasInconsistency Indirectness ImprecisionOther
considerationsPCV21 comparisonRelative
(95% CI)Absolute
(95% CI)
VT-IPD, VT -nonbacteremic pneumococcal pneumonia, VT -pneumococcal mortality outcome (Assessed with: Immunogenicity)
51-5Randomized
studiesNot
seriousNot serious SeriousaNot serious Not serious 123 - 1161 58 - 1162• V116 met non -inferiority criteriab for
9/9 shared and superiority criteriac
for 12/12 unique serotypes vs.
PPSV23
• V116 met non -inferiority criteriad for
10/10 shared and superiority
criteriae 10/11 unique serotypes vs.
PCV20
• V116 had higher immune responses
for 1 -4/6 shared and all unique
serotypes vs. PCV15Moderate CriticalGRADE Summary of Findings Table
PICO 1: Adults currently recommended to receive PCV
a. These are all immunogenicity studies and there are no correlates of protection for some critical outcomes considered.
b. Noninferiority for GMT ratio was defined as the lower bound of the 95% CI of the estimated OPA GMT ratio ({V116:PPSV23} to be > 0.33.
c. Superiority for GMT ratio was defined as the lower bound of the 95% CI of the estimated OPA GMT ratio [V116:PPSV23] to be > 1.0.
d. Noninferiority for GMT ratio was defined as the lower bound of the 2 sided 95% CI of the OPA GMT ratio [V116 / PCV20] to be > 0.5.
e. Superiority for GMT ratio was defined as the lower bound of the 2 sided 95% CI of the OPA GMT ratio [V116 / PCV20] to be >2.0.
References
1. Platt H, Omole T, Cardona J, Fraser NJ, Mularski  RA, Andrews C, Daboul  N, Gallagher N, Sapre A, Li J, Polis A, Fernsler  D, Tamms G, Xu W, Murphy R, Skinner J, Joyce J, Musey L. Safety, tolerability, and immunogenicity of a 21- valent pneumococcal c onjugate vaccine,
V116, in healthy adults: phase 1/2, randomised, double- blind, active comparator -controlled, multicentre, U.S.- based trial. Lancet Infect Dis. 2023 Feb;23(2):233- 246. doi: 10.1016/S1473- 3099(22)00526 -6. Epub 2022 Sep 15. PMID: 36116461.
2. V116- 003. A clinical study to evaluate the safety, tolerability, and immunogenicity of V116 compared to PCV20 in pneumococcal vaccine -naïve adults
3. V116- 006. A Phase 3 Clinical Study to Evaluate the Safety, Tolerability, and Immunogenicity of V116 in Pneumococcal Vaccine- Experienced Adults 50 Years of Age or Older
4. V116- 007. A Phase 3, Multicenter, Randomized, Double- blind, Active Comparator - Controlled Study to Evaluate the Safety, Tolerabi lity, and Immunogenicity of V116 in Adults Living With HIV
5. V166- 005. A clinical study comparing the immunogenicity and safety of V116 when administered concomitantly with inactivated infl uenza vaccine
Certainty assessment № of patients Effect
Certainty Importance№ of
studiesStudy designRisk of
biasInconsistency Indirectness ImprecisionOther
considerationsPCV21 comparisonRelative
(95% CI)Absolute
(95% CI)
Serious adverse events following immunization
61-6Randomized
studiesNot
seriousNot serious Not serious SeriousfNot serious 57/4445
(1.3%)63/2962
(2.1%)Absolute % difference for SAEs across
studies is -0.8%; two SAEs deemed
vaccine -relatedg in the V116 group
reportedModerate CriticalGRADE Summary of Findings Table
PICO 1: Adults currently recommended to receive PCV
f. few vaccine- related serious adverse events reported.
g. Bronchospasm (V116- 005): 50- year-old female in the sequential group with bronchospasm within 30 minutes after the 2ndvaccination (V116); duration 23 hours; resolved; Injection site cellulitis (V116- 006): 67- year-old female in Cohort 1 (prior PPSV23) with i njection site cellulitis
on Day 6; duration 1.57 weeks; resolved (Merck, unpublished).
References
1. Platt H, Omole T, Cardona J, Fraser NJ, Mularski  RA, Andrews C, Daboul  N, Gallagher N, Sapre A, Li J, Polis A, Fernsler  D, Tamms G, Xu W, Murphy R, Skinner J, Joyce J, Musey L. Safety, tolerability, and immunogenicity of a 21- valent pneumococcal c onjugate vaccine,
V116, in healthy adults: phase 1/2, randomised, double- blind, active comparator -controlled, multicentre, U.S.- based trial. Lancet Infect Dis. 2023 Feb;23(2):233- 246. doi: 10.1016/S1473- 3099(22)00526 -6. Epub 2022 Sep 15. PMID: 36116461.
2. V116- 003. A clinical study to evaluate the safety, tolerability, and immunogenicity of V116 compared to PCV20 in pneumococcal vaccine -naïve adults
3. V116- 006. A Phase 3 Clinical Study to Evaluate the Safety, Tolerability, and Immunogenicity of V116 in Pneumococcal Vaccine- Experienced Adults 50 Years of Age or Older
4. V116- 007. A Phase 3, Multicenter, Randomized, Double- blind, Active Comparator - Controlled Study to Evaluate the Safety, Tolerabi lity, and Immunogenicity of V116 in Adults Living With HIV
5. V166- 005. A clinical study comparing the immunogenicity and safety of V116 when administered concomitantly with inactivated infl uenza vaccine
6. V116- 004. A Phase 3 Randomized, Double- blind, Active Comparator -controlled, Lot to- Lot Consistency Study to Evaluate the Safety,  Tolerability, and Immunogenicity of V116 in Adults 18 to 49 Years of Age.
Certainty assessment № of patients Effect
Certainty Importance № of
studiesStudy designRisk
of
biasInconsistency Indirectness ImprecisionOther
considerationsPCV21 comparisonRelative
(95% CI)Absolute
(95% CI)
VT-IPD, VT -nonbacteremic pneumococcal pneumonia, VT -pneumococcal mortality outcome (Assessed with: Immunogenicity)
21-2Randomized
studiesNot
seriousNot serious SeriousaNot serious Not serious 252 - 1161 254 - 1162 • V116 met non -inferiority
criteriab for 9/9 shared and
superiority criteriac for 12/12
unique serotypes vs. PPSV23
• V116 met non -inferiority
criteriad for 10/10 shared and
superiority criteriae 10/11
unique serotypes vs. PCV20Moderate CriticalGRADE Summary of Findings Table
PICO2: Adults aged 50–64 years, no risk- based indications
a. These are all immunogenicity studies and there are no correlates of protection for some critical outcomes considered.
b. Noninferiority for GMT ratio was defined as the lower bound of the 95% CI of the estimated OPA GMT ratio ({V116:PPSV23} to be > 0.33.
c. Superiority for GMT ratio was defined as the lower bound of the 95% CI of the estimated OPA GMT ratio [V116:PPSV23] to be > 1.0.
d. Noninferiority for GMT ratio was defined as the lower bound of the 2 sided 95% CI of the OPA GMT ratio [V116 / PCV20] to be > 0.5.
e. Superiority for GMT ratio was defined as the lower bound of the 2 sided 95% CI of the OPA GMT ratio [V116 / PCV20] to be >2.0.
References
1. Platt H, Omole T, Cardona J, Fraser NJ, Mularski  RA, Andrews C, Daboul  N, Gallagher N, Sapre A, Li J, Polis A, Fernsler  D, Tamms G, Xu W, Murphy R, Skinner J, Joyce J, Musey L. Safety, tolerability, and immunogenicity of a 21-
valent pneumococcal conjugate vaccine, V116, in healthy adults: phase 1/2, randomised, double- blind, active comparator -controlled, multicentre, U.S.- based trial. Lancet Infect Dis. 2023 Feb;23(2):233 -246. doi: 10.1016/S1473-
3099(22)00526 -6. Epub 2022 Sep 15. PMID: 36116461.
2. V116- 003. A clinical study to evaluate the safety, tolerability, and immunogenicity of V116 compared to PCV20 in pneumococcal vaccine- naïve adults
Certainty assessment № of patients Effect
Certainty Importance № of
studiesStudy designRisk
of
biasInconsistency Indirectness ImprecisionOther
considerationsPCV21 comparisonRelative
(95% CI)Absolute
(95% CI)
Serious adverse events following immunization
21-2Randomized
studiesNot
seriousNot serious Not serious SeriousfNot serious 23/1431
(1.6%)27/1429
(1.9%)Absolute % difference for SAEs across
studies is -0.3%; no vaccine -related
serious adverse events reportedModerate CriticalGRADE Summary of Findings Table
PICO2: Adults aged 50–64 years, no risk- based indications
f. No vaccine -related serious adverse events reported.
References
1. Platt H, Omole T, Cardona J, Fraser NJ, Mularski  RA, Andrews C, Daboul  N, Gallagher N, Sapre A, Li J, Polis A, Fernsler  D, Tamms G, Xu W, Murphy R, Skinner J, Joyce J, Musey L. Safety, tolerability, and immunogenicity of a 21-
valent pneumococcal conjugate vaccine, V116, in healthy adults: phase 1/2, randomised, double- blind, active comparator -controlled, multicentre, U.S.- based trial. Lancet Infect Dis. 2023 Feb;23(2):233 -246. doi: 10.1016/S1473-
3099(22)00526 -6. Epub 2022 Sep 15. PMID: 36116461.
2. V116- 003. clinical study to evaluate the safety, tolerability, and immunogenicity of V116 compared to PCV20 in pneumococcal vacc ine-naïve adults
Certainty assessment № of patients Effect
Certainty Importance
№ of
studiesStudy designRisk of
biasInconsistency Indirectness ImprecisionOther
considerationsPCV21 comparisonRelative
(95% CI)Absolute
(95% CI)
VT-IPD, VT -nonbacteremic pneumococcal pneumonia, VT -pneumococcal mortality outcome (Assessed with: Immunogenicity)
11Randomized
studiesNot
seriousNot serious SeriousaNot serious Not serious 184 - 198 550 - 575 V116 met criteria for
immunobridgingb to 50 -
64y for all serotypesModerate CriticalGRADE Summary of Findings Table
PICO3: Adults aged 19–49 years, no risk- based indications
a. These are all immunogenicity studies and there are no correlates of protection for some critical outcomes considered.
b. Immunobridging for GMT ratio was defined as the lower bound of the 2 sided 95% CI of the OPA GMT ratio [V116 18 to 49 group/V116 50 to 64 gr oup] to be >0.5.
References
1. V116 -003. A clinical study to evaluate the safety, tolerability, and immunogenicity of V116 compared to PCV20 in pneumococcal vaccine -naïve adults
Certainty assessment № of patients Effect
Certainty Importance№ of
studiesStudy designRisk
of
biasInconsistency Indirectness ImprecisionOther
considerationsPCV21 comparisonRelative
(95% CI)Absolute
(95% CI)
Serious adverse events following immunization
11Randomized
studiesNot
seriousNot serious Not serious SeriouscNot serious 1/200
(0.5%)3/100
(3.0%)Absolute % difference
for SAEs is -2.5%; no
vaccine -related
serious adverse events
reportedModerate CriticalGRADE Summary of Findings Table
PICO3: Adults aged 19–49 years, no risk- based indications
c. No vaccine -related serious adverse events reported
References
1. V116 -003. clinical study to evaluate the safety, tolerability, and immunogenicity of V116 compared to PCV20 in pneumococcal vacc ine-naïve adults
PICO1: Adults currently recommended to receive PCV
Type Outcome ImportanceIncluded in evidence
profile Certainty of evidence
BenefitsVT- IPD Critical No* Moderate
VT-pneumonia Critical No* Moderate
VT- pneumococcal
deathsCritical No* Moderate
HarmsSerious adverse events
following
immunizationCritical Yes Moderate
*No clinical evidence available; immunogenicity data used as proxy for vaccine effectiveness of outcomes
PICO2: Adults aged 50 –64 years, no risk -based
indications
Type Outcome ImportanceIncluded in evidence
profile Certainty of evidence
BenefitsVT- IPD Critical No* Moderate
VT-pneumonia Critical No* Moderate
VT- pneumococcal
deathsCritical No* Moderate
HarmsSerious adverse events
following
immunizationCritical Yes Moderate
*No clinical evidence available; immunogenicity data used as proxy for vaccine effectiveness of outcomes
PICO3: Adults aged 19– 49 years, no risk -based
indications
Type Outcome ImportanceIncluded in evidence
profile Certainty of evidence
BenefitsVT- IPD Critical No* Moderate
VT-pneumonia Critical No* Moderate
VT- pneumococcal
deathsCritical No* Moderate
HarmsSerious adverse events
following
immunizationCritical Yes Moderate
*No clinical evidence available; immunogenicity data used as proxy for vaccine effectiveness of outcomes

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. Preliminary Work Group Interpretations of EtR  and  Next Steps February 2024, ACIP Meeting February 29, 2024 Miwako Kobayashi, MD, MPH, FACP , FIDSA 1.Should PCV21 be…


01 Vaxelis Loehr 508

Introduction and Terms of Reference:
Combined Diphtheria and Tetanus Toxoids and Acellular
Pertussis, Inactivated Poliovirus, Haemophilus  influenzae
Type B Conjugate, and Hepatitis B vaccine (Vaxelis)
Jamie Loehr
Interim Chair, ACIP Meningococcal/Hib Vaccines Work Group
February 29, 2024National Center for Immunization & Respiratory Diseases
ACIP Meningococcal/Hib Vaccines Work Group
▪ ACIP Members on the WG
•Jamie Loehr (Interim Chair)
•Wilbur Chen
▪ Ex Officio WG Members
•Margaret Bash (FDA)
•Matthew Clark (IHS)
•Mark Connelly (FDA)
•Francisco Leyva (NIH)
▪ WG Liaisons and Consultants
•Amra Resic  (AAFP)
•Samir Shah (AAP)
•Barb Fluty (ACHA)
•Karyn Lyons (AIM)
•Paul Cieslak (CSTE)
•Kathy Hsu (IDSA)
•Joseline Zafack (NACI)
•Jeff Goad (NFID)
•Jessica Cataldi (PIDS)
•Amy Middleman (SAHM)
•Kathy Poehling (Wake Forest)
•Lynn Bahta (Minnesota Department of Health)
•David Stephens (Emory)▪ CDC Contributors
•Jennifer Collins (DBD/NCIRD)
•Sarah Schillie (DBD/NCIRD)
•Lucy McNamara (DBD/NCIRD)
•LeAnne Fox (DBD/NCIRD)
•Susan Hariri (DBD/NCIRD)
•Amy Rubis (DBD/NCIRD)
•Noele Nelson (DBD/NCIRD)
•Alison Albert (DBD/NCIRD)
•Angela Jiles (DBD/NCIRD)
•Marc Fischer (DIDRI/NCEZID)
•Jonathan Duffy (DHQP/NCEZID)
•Pedro Moro (DHQP/NCEZID)
•Tanya Myers (DHQP/NCEZID)
•Liz Velazquez (ISD/NCIRD)
•Jessica MacNeil (ACIP Secretariat)
•Hannah Rosenblum (ACIP Secretariat)
•Melinda Wharton (ACIP Secretariat)
▪ GRADE/ EtR Support
•Doug Campos -Outcalt (Arizona)
•Rebecca Morgan (Case Western Reserve)
2
Background
▪PRP-OMP ( PedvaxHIB ) is preferentially recommended for American
Indian and Alaska Native (AI/AN) infants
•It provides a protective antibody response after the first dose
•Historically, Hib meningitis peaked at an earlier age among AI/AN
infants
▪Vaxelis (DTaP -IPV-Hib-HepB ) does not currently have a preferential
recommendation for AI/AN infants because
•It contains PRP -OMP in a lower amount than PedvaxHIB
•Post -dose 1 immunogenicity data were not previously available
3
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
Policy question
Should Vaxelis (DTaP -IPV-Hib-HepB ) be included with
PedvaxHIB  in the preferential recommendation for
American Indian and Alaska Native (AI/AN) infants?
4
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
Work Group activities
▪Review the epidemiology of invasive Hib disease in AI/AN
populations and evidence supporting the existing preferential
recommendation for PedvaxHIB
▪Review clinical trial data on post -dose 1 immunogenicity of Vaxelis
vs. PedvaxHIB
▪Develop draft policy recommendation based on grading of
recommendations, assessment, development, and evaluation
(GRADE) and the evidence to recommendations ( EtR) framework
5The use of trade names is for identification purposes only and does not imply endorsement by CDC.
6Today’s agenda
All topics  will be presented for information and discussionTopic Presenter
Background on Hib disease and
vaccination among American Indian
and Alaska Native populationsDr. Jennifer Collins (CDC/NCIRD)
Immunogenicity of H. influenzae type b
PRP-OMP vaccines in American Indian
and Alaska Native infantsDr. Laura Hammitt (Johns Hopkins
Bloomberg School of Public Health
– Center for Indigenous Health)
Work Group Considerations Dr. Jennifer Collins (CDC/NCIRD)
Next steps
24▪Present evidence to recommendations ( EtR) framework and draft
policy recommendations for a vote in June
7

Summary: Introduction and Terms of Reference: Combined Diphtheria and Tetanus Toxoids and Acellular  Pertussis, Inactivated Poliovirus, Haemophilus  influenzae  Type B Conjugate, and Hepatitis B vaccine (Vaxelis)  Jamie Loehr Interim Chair, ACIP Meningococcal/Hib Vaccines Work Group February 29, 2024National Center for Immunization & Respiratory Diseases ACIP Meningococcal/Hib Vaccines Work Group ▪ ACIP Members on the WG •Jamie Loehr (Interim Chair) •Wilbur Chen ▪ Ex Officio WG Members •Margaret Bash…


02 Vaxelis Collins 508

Background on invasive Hib disease and
vaccination among American Indian and
Alaska Native populations
Jennifer Collins MD, MSc
Co-Lead, ACIP Hib/Meningococcal Vaccines Work Group
February 29, 2024National Center for Immunization & Respiratory Diseases
Background
3▪Gram -negative bacilli
▪Originally thought to be the cause of influenza
▪Abbreviated “ H. flu ” or Hi
▪Infections range from mild to severe invasive disease
Haemophilus  influenzae
NTUnencapsulated
(Non -typeable)
b a c d e fEncapsulated
(6 serotypes based on polysaccharide antigens)Classification of H. influenzae
4
H. influenzae serotype b (Hib) is most virulent and
is the only type preventable through vaccination
NTUnencapsulated
(Non -typeable)
b a c d e fEncapsulated
(6 serotypes based on polysaccharide antigens)
•Before the introduction of effective vaccines, Hib was the leading cause of
bacterial meningitis and other invasive bacterial disease in the United
States, primarily among children aged <5 years
5
6Risk factors for invasive Hib disease in the pre -
vaccine era
Immunocompromising conditions
•HIV infection
•Asplenia / Sickle cell disease
•IgG deficiency
•Early component complement
deficiency
•Hematopoietic  stem cell
transplantation
•ChemotherapyDemographic factors
•Male sex
•Race/Ethnicity
•American Indian
•Alaska Native
•Black
•Social factors
•Household c rowding
•Large household size
•Low SES
•School -aged siblings
•Daycare attendance
6
Bacteremic
pneumoniaMost common clinical syndromes of invasive Hib
disease in the post -vaccine era
Meningitis Bacteremia
without a focus
7
Estimated incidence of invasive Hib disease in children
aged <5 years decreased dramatically  after
introduction of Hib vaccines
051015202530
1980 1985 1990 1995 2000 2005 2010Estimated
incidence per
100,000
populationConjugate vaccine licensed for use
in children aged ≥18 months
Conjugate vaccine licensed for use
in infants aged ≥2 monthsPolysaccharide vaccine licensed for
use in children aged ≥18 months
8
9▪Capsular polysaccharide (PRP) conjugated to carrier proteins
–Tetanus toxoid (PRP -T)
–Outer membrane protein of meningococcal serogroup B (PRP -OMP)
▪Highly immunogenic via activation of T -cell dependent immunity
–95% of infants develop protective antibody levels after a primary series
–No cross protection against non -b serotypes/ NTHi
▪Estimated clinical efficacy 95% ─100%
▪Invasive Hib disease is uncommon in children who are fully vaccinated Hib polysaccharide conjugate vaccines
remain the primary prevention strategy for Hib
9
10Current Hib vaccines in the United States
Vaccine Product Trade Name Primary series Booster dose
Monovalent vaccines
PRP-OMP PedvaxHIB * 2, 4 months 12–15 months
PRP-T ActHIB 2, 4, 6 months 12–15 months
PRP-T Hiberix 2, 4, 6 months 12–15 months
Combination vaccines**
DTaP -IPV/Hib Pentacel 2, 4, 6 months 12–15 months
DTaP -IPV-Hib-HepB Vaxelis 2, 4, 6 months ***
*Recommended vaccine for American Indian/Alaska Native children
**Hib component of Pentacel  is PRP -T. Hib component of Vaxelis is PRP -OMP .
***Vaxelis is not recommended for the booster dose. A different Hib -containing vaccine should be administered as a booster at 12 –15 months.
10
Invasive Hib disease disproportionately
affects American Indian and Alaska
Native populations
12051015202530
1980 1985 1990 1995 2000 2005 2010Incidence declined >99%Incidence of invasive Hib disease among children aged
<5 years declined >99% with introduction of Hib vaccines
12Estimated
incidence  per
100,000 of
invasive Hib
disease among
children aged
<5 years
13050100150200250300
1980 1985 1990 1995 2000 2005 2010U.S. childrenExpanding the y -axis…
13Estimated
incidence  per
100,000 of
invasive Hib
disease among
children aged
<5 years
14050100150200250300
1980 1985 1990 1995 2000 2005 2010280
American Indian and
Alaska Native
children
U.S. childrenIncidence among AI/AN children aged <5 years was >10x
the incidence among U.S. children aged <5 years overall
14Estimated
incidence  per
100,000 of
invasive Hib
disease among
children aged
<5 years
15Incidence of Hib disease among AI/AN children
aged <5 years declined >98% with Hib vaccination
050100150200250300
Pre-vaccine era Post-vaccine era
15Estimated i ncidence
per 100,000 of
invasive Hib disease
among AI/AN
children aged
<5 years
Incidence per
100,000 of invasive
H. influenzae
disease by type
among children
aged <5 years,
2011 –2020
012345
Hia Hib Hif NTHiAI/AN Non-AI/ANIncidence of invasive H. influenzae disease remains
substantially higher among American Indian and
Alaska Native children  compared with non-Native
children
5.1
2.5
0.92.1
0.6 0.080.31.3
16
Incidence per
100,000 of invasive
H. influenzae
disease by type
among children
aged <5 years,
2011 –2020
012345
Hia Hib Hif NTHiAI/AN Non-AI/AN
17AI/AN children have 31 -fold higher incidence of
invasive Hib disease than non -Native children
31x
In the pre -vaccine era, the incidence of Hib meningitis
peaked at a younger age among AI/AN populations
than the general U.S. population
18 Data from Ward JI, et al.  Lancet . 1981. 1(8233); 1281 –5. Graph credit: Laura Hammitt’s  February 2019 ACIP Meeting presentation
Cases per 100,000
(1971–1977)
19Invasive Hib disease among AI/AN children
aged <5 years―Active Bacterial Core
surveillance, 2003 –2023*
Characteristic N=28
Patient age, months
     Median
     IQR
     Range 12
5–31
0–56
Unvaccinated , n (%) 9 (31)
Syndrome
     Meningitis
     Pneumonia
     Cellulitis
     Bacteremia without a focus 13 (45)
12 (41)
3 (10)
1 (3)
19*2022 and 2023 data are preliminary
Hib vaccination among American Indian
and Alaska Native infants
Briere EC, et al. Prevention and Control of Haemophilus  influenzae Type b Disease: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recommendations and Reports . 63(RR01);1 -14PedvaxHIB  (PRP-OMP) is preferentially recommended
for AI/AN infants
•Vaccination with a 2 dose primary series of a Hib vaccine that contains
PRP-OMP ( PedvaxHIB ) is preferred for AI/AN infants to provide early
protection because this vaccine produce a protective antibody response
after the first dose
•A booster dose (dose 3) of Hib vaccine is recommended at age 12
through 15 months; for the booster dose, there is no preferred vaccine
formulation
21
22
PRP-OMP provides earlier protection
*PRP ≥0.15 ug/ml and ≥1.0 ug/ml are correlates of short -term, and long -term protection, respectively.
Watt JP , et al. Global reduction of Hib disease: what are the next steps? The Journal of Pediatrics 2003. 22PRP-OMP produces a
protective antibody
response after the
first dose
Anti-PRP GMT
µg/mL*
After dose 1
(age 2 months)Before After dose 2
(age 4 months)After dose 3
(age 6 months)Final titers
are higher
with PRP -T
23The incidence of invasive Hib disease in Alaska
Native populations increased in late 1990s amid
vaccine policy changes
Singleton R et al. The Alaska Haemophilus  influenzae Type b Experience: Lessons in Controlling a Vaccine -Preventable Disease. Pediatrics. 2006 Aug;118(2):e421 -9Invasive Hib disease
rates per 100 000 in
Alaska Native and
non-Native children
aged 5 years, 1980 –
2004
23
24
Singleton R et al. The Alaska Haemophilus  influenzae Type b Experience: Lessons in Controlling a Vaccine -Preventable Disease. Pediatrics. 2006 Aug;118(2):e421 -9
Universal Hib
vaccination:
HbOC  in January
PRP-OMP in JulyCombination vaccine
DTP-HbOC  replaced
PRP-OMP
Change to PRP -OMP for
dose 1 followed by HbOC
for doses 2 –4
HbOC  = Hib oligosaccharide CRM 197 vaccine
DTP =  Diphtheria, tetanus toxoids, pertussis Timeline of Hib vaccine policy changes in Alaska
.Change to PRP -OMP for
all Hib doses
24
25Vaccine status among children aged <10 years
with invasive Hib disease in Alaska, 1991 –2004
Singleton R et al. The Alaska Haemophilus  influenzae Type b Experience: Lessons in Controlling a Vaccine -Preventable Disease. Pediatrics. 2006 Aug;118(2):e421 -9
▪During  1996–2000 , a greater
proportion of cases
–Occurred among Alaska
Native children
–Occurred among partially
immunized children
–Were considered true vaccine
failures
25
26Vaccine administration errors may have
contributed to some cases when  both PRP -OMP
and HbOC  were used
Singleton R et al. The Alaska Haemophilus  influenzae Type b Experience: Lessons in Controlling a Vaccine -Preventable Disease. Pediatrics. 2006 Aug;118(2):e421 -9▪October 1997 –December 2000
–14 cases occurred in Alaska Native children aged <5
years
–3 children (21%) had inadvertently received HbOC  for
their first and only dose
26
27Increases in Hib disease in Alaska during
1996–2000 were attributed to
▪Use of HbOC , which  did not achieve short -term
protective antibody concentrations (0.15 µg/mL) until the
third dose
▪Low rates of on -time immunization
Singleton R et al. The Alaska Haemophilus  influenzae Type b Experience: Lessons in Controlling a Vaccine -Preventable Disease. Pediatrics. 2006 Aug;118(2):e421 -9 27
28National Immunization Survey –Child
Estimated vaccination coverage with Hib full series* by age 24
months among American Indian or Alaska Native children by
birth year
Birth yearⴕ% 95% CI
2016 77.0 64.8 –87.4
2017 69.6 55.1 –83.0
2018 76.3 66.0 –85.4
2019 69.9 59.5 –79.7
2020 67.5 54.6 –79.7
* Hib Full Series: primary series and booster dose, which includes receipt of ≥3 or ≥4 doses, depending on product type recei ved.
† Data for the 2016 birth year are from survey years 2017, 2018, and 2019; data for the 2017 birth year are from survey years  2018, 2019, and 2020; data for the
2018 birth year are from survey years 2019, 2020, and 2021; data for the 2019 birth year are from survey years 2020, 2021, an d 2022; data for the 2020 birth year
are considered preliminary and are from survey years 2021 and 2022 (2023 data are not yet available).
Hill HA et al. Vaccination Coverage by Age 24 Months Among Children Born in 2019 and 2020 — National Immunization Survey -Child, United States, 2020 –2022 . MMWR Weekly / November 3, 2023 / 72(44);1190 –1196. 28
29National Immunization Survey –Child:
In 2019–2020, American Indian/Alaska Native children were
less likely than White children to have received the Hib full
series* by age 24 months
Race, Ethnicity 2019–2020 (prelim)ⴕ
%, 95% CIDifference (White –AI/AN)
2019–2020 (prelim)ⴕ
% 95% CI p-value
White, non -Hispanic 80.8 (79.4 –82.1) REF REF REF
American Indian or Alaska
Native, non -Hispanic68.7 (60.3 –76.8) 12.1 (3.6–20.5) 0.01
*Hib full series: primary series and booster dose, which includes receipt of ≥3 or ≥4 doses, depending on product type receiv ed.
ⴕData for the 2019 birth year are from survey years 2020, 2021, and 2022; data for the 2020 birth year are considered prelimin ary and are
from survey years 2021 and 2022 (2023 data are not yet available).
Hill HA et al. Vaccination Coverage by Age 24 Months Among Children Born in 2019 and 2020 — National Immunization Survey -Child, United States, 2020 –2022. MMWR Weekly / November 3, 2023 / 72(44);1190 –1196. 29
Vaxelis (DTaP -IPV-Hib-HepB )
31Vaxelis (DTaP -IPV-Hib-HepB ) is newer
▪Licensed in December 2018
▪ACIP voted to include in VFC in June 2019
▪More than 6.2 million doses distributed in the United
States as of Q4 2023
*Data provided by the manufacturer.31 The use of trade names is for identification purposes only and does not imply endorsement by CDC.
32Vaxelis (DTaP -IPV-Hib-HepB ) does not
currently have a preferential recommendation
for AI/AN infants
Vaccine Product Trade Name PRP OMP
PRP-OMP PedvaxHIB 7.5 mcg 125 mcg
DTaP -IPV-Hib-HepB Vaxelis 3 mcg 50 mcg
32▪Post -dose 1 immunogenicity data not previously available
▪Lower dose of PRP -OMP than PedvaxHIB
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
33In Phase III clinical
trials, Hib antibody
responses after the
3-dose primary
series were non -
inferior to licensed
comparator
vaccines
21
Vaxelis group
Control group
Marshall GS, et al. Immunogenicity, safety and tolerability of a hexavalent vaccine in infants. Pediatrics 2015;136:e323 –32.33- Vaxelis group received DTaP5 -IPV-Hib-HepB, PCV13, and RV5 at 2, 4, and 6 months of age followed by DTaP5, Hib -OMP, and PCV13 at 15 months of a ge.
- Control group  received DTaP5 -IPV/Hib,PCV13, and RV5 at 2, 4, and 6 months of age, with HepB  at 2 and 6 months of age, followed by DTaP5, Hib -TT, and PCV13 at 15 months of age.
- PRP ≥0.15 ug/ml and ≥1.0 ug/ml are correlates of short -term, and long -term protection, respectively.
- The use of trade names is for identification purposes only and does not imply endorsement by CDC.
.
34Safety of Vaxelis (DTaP -IPV-Hib-HepB )
34▪In clinical trials, the safety profile was consistent with that of licensed
comparator vaccines except higher rate of fever than with DTaP -IPV/Hib
(47.1% –47.4% vs. 33.2% –34.4%)1,2; rates of fever -related medical events
were similar between groups
▪Post -licensure analysis of VAERS data from June 26, 2019 – June 16, 2023
did not identify new or unexpected safety issues
1Marshall GS, et al. Immunogenicity, safety and tolerability of a hexavalent vaccine in infants. Pediatrics 2015;136:e323 –32.
2Block SL, et al. Lot -to-lot consistency, safety, tolerability and immunogenicity of an investigational hexavalent vaccine in U.S . infants. Pediatr  Infect Dis J 2017;36:202 –8.

35Vaxelis protects against 6 infections with fewer
injections
Pediarix  is a combination vaccine that protects against diphtheria, tetanus, pertussis, polio, and hepatitis B.
DTaP is a vaccine that protects against diphtheria, tetanus, and pertussis. The 4th dose of DTaP is recommended at age 15 –18 months.
IPV is inactivated polio vaccine.Vaxelis  Vaxelis   VaxelisOption 2 months 4 months 6 months 12–15
monthsTotal shots
1 Vaxelis Vaxelis Vaxelis PedvaxHIB
DTaP5
2 PedvaxHIB
PediarixPedvaxHIB
Pediarix PediarixPedvaxHIB
DTaP7
3 PedvaxHIB
DTaP
IPV
HepBPedvaxHIB
DTaP
IPVDTaP
IPV
HepBPedvaxHIB
DTaP12
The use of trade names is for identification purposes only and does not imply endorsement by CDC. 35
Policy question
▪Should Vaxelis (DTaP -IPV-Hib-HepB ) be included with
PedvaxHIB  in the preferential recommendation for
American Indian and Alaska Native infants?
The use of trade names is for identification purposes only and does not imply endorsement by CDC. 36
Acknowledgments
▪ ACIP Members on the WG
– Jamie Loehr (Interim Chair)
– Wilbur Chen
▪ Ex Officio WG Members
– Margaret Bash (FDA)
– Matthew Clark (IHS)
– Mark Connelly (FDA)
– Francisco Leyva (NIH)
▪ WG Liaisons and Consultants
– Amra Resic  (AAFP)
– Samir Shah (AAP)
– Barb Fluty (ACHA)
– Karyn Lyons (AIM)
– Paul Cieslak (CSTE)
– Kathy Hsu (IDSA)
– Joseline Zafack (NACI)
– Jeff Goad (NFID)
– Jessica Cataldi (PIDS)
– Amy Middleman (SAHM)
– Kathy Poehling (Wake Forest)
– Lynn Bahta (Minnesota Department of Health)
– David Stephens (Emory)▪ CDC Contributors
– Lucy McNamara (DBD/NCIRD)
– Sarah Schillie (DBD/NCIRD)
– LeAnne Fox (DBD/NCIRD)
– Susan Hariri (DBD/NCIRD)
– Amy Rubis (DBD/NCIRD)
– Noele Nelson (DBD/NCIRD)
– Alison Albert (DBD/NCIRD)
– Angela Jiles (DBD/NCIRD)
– Marc Fischer (DIDRI/NCEZID)
– Jonathan Duffy (DHQP/NCEZID)
– Pedro Moro (DHQP/NCEZID)
– Tanya Myers (DHQP/NCEZID)
– Liz Velazquez (ISD/NCIRD)
– Jessica MacNeil (ACIP Secretariat)
– Hannah Rosenblum (ACIP Secretariat)
– Melinda Wharton (ACIP Secretariat)
▪ GRADE/ EtR Support
– Doug Campos -Outcalt (Arizona)
– Rebecca Morgan (Case Western Reserve)
Thank you!
Questions?

Summary: Background on invasive Hib disease and  vaccination among American Indian and  Alaska Native populations Jennifer Collins MD, MSc Co-Lead, ACIP Hib/Meningococcal Vaccines Work Group February 29, 2024National Center for Immunization & Respiratory Diseases Background 3▪Gram -negative bacilli  ▪Originally thought to be the cause of influenza ▪Abbreviated “ H. flu ” or Hi ▪Infections range from mild to severe invasive disease Haemophilus  influenzae  NTUnencapsulated  (Non -typeable) b a c d e…


03 Vaxelis Hammitt 508

The HibVax Study
Immunogenicity of H. influenzae type b PRP -OMP
vaccines in American Indian and Alaska Native infants
Laura Hammitt, MD
Associate Professor, JHSPH
Infectious Disease Program Lead, Center for Indigenous Health
Johns Hopkins Bloomberg School of Public Health
On behalf of the study team in Navajo Nation and Anchorage, Alaska
Disclosures/Disclaimers
▪This study was supported in part by a research grant from the Investigator -
Initiated Studies Program of Merck Sharp & Dohme LLC, a subsidiary of Merck
& Co., Inc. Rahway, NJ 07065 USA, acting on behalf of a joint venture with Sanofi
known as MSP Vaccine Company.
▪Research grants to my institution from AstraZeneca, Merck, Pfizer, CDC, NIH.
▪The findings and conclusions in this report are those of the authors and do not
necessarily represent the official position of the Indian Health Service or the
Centers for Disease Control and Prevention.
2
Preferential recommendation for PRP -OMP Hib
conjugate vaccines in AI/AN infants
▪Disease at a young age in the
pre-vaccine era
▪Robust protection following
the first dose
▪Immunogenicity
▪Efficacy
▪Re-emergence of Hib disease
in AN infants following use of
non -PRP -OMP vaccines   050010001500200025003000
0-1 2-3 4-5 6-7 8-9 10-11 12-23 24-48Cases per 100,000
Age (months)Alaska Native Navajo Nation General US
Ward JI et al., Lancet , 1981; 1281 -1284.H. influenzae  meningitis in children <5 years,
1971-1977
3
Preferential recommendation for PRP -OMP Hib
conjugate vaccines in AI/AN infants
Table 3. Efficacy Analysis of H. influenzae Type b OMPC Vaccine*
Time of Disease OnsetCases of H.
influenzae Efficacy
Estimatep-value95% CI
Vaccine Placebo
(n/total) (%)
At least 1 dose
Onset before 18 mo. 1/2588 22/2602 95 <0.001 72-99
Onset before 15 mo. 0/2588 21/2602 100 <0.001 81-100
Onset before 2nd dose 0/2588 8/2602 100 0.005 41-100
Two doses
Onset before 18 mo. 1/2056 14/2105 93 <0.001 53-98
Onset before 15 mo. 0/2056 13/2105 100 <0.001 67-100
*Intention -to-treat analysis - included all infants enrolled.
Santosham  et al., N Engl J Med 1991; 324:1767 -17724▪Disease at a young age in the
pre-vaccine era
▪Robust protection following
the first dose
▪Immunogenicity
▪Efficacy
▪Re-emergence of Hib disease
in AN infants following use of
non -PRP -OMP vaccines
Preferential recommendation for PRP -OMP Hib
conjugate vaccines in AI/AN infants
Invasive Hib Disease Children Aged <5 Years
Alaska, 1980 - 2018
Figure courtesy of Rosalyn Singleton; Singleton, et al. J Pediatr  2000; 137:313 -205▪Disease at a young age in the
pre-vaccine era
▪Robust protection following
the first dose
▪Immunogenicity
▪Efficacy
▪Re-emergence of Hib disease
in AN infants following use of
non -PRP -OMP vaccines
Invasive Hib disease in children <5 years
020406080100Incidence
(cases/per 100,000)Navajo Nation General US*Hib PRP -OMP
vaccine introductionAverage number Hib cases in U5 children
per year in Navajo Nation:
1988 - 1990: 19 cases/ yr
1993 - 2023: <2 cases/yr
90%
decline
CIH/Navajo Epidemiology Center Active Bacterial Surveillance data; Navajo Research Conference 20216
Invasive Hib disease in AI/AN children <5 years
Navajo Nation and White Mountain Apache Tribal Lands
2004 -2023 (N=25)
0102030405060Age (months)Vaccination history in Hib cases
<5 years
Un-
vaccinated
(n=4)Up to date
for age
(n=7)Fully
vaccinated
(n=14)Average age 21 months
Median age
(IQR)14 months
(9-37 months)
Age range 2-52 months
Clinical
syndromeMeningitis: 28%
Pneumonia: 40%
7IQR: interquartile range
Combination vaccines → fewer shots, fewer missed doses,
lower administrative burdenPedvaxHIB ®
(PRP -OMP Hib vaccine)Vaxelis®
(DTaP -IPV-Hib-HepB )
Contents Single Antigen Hexavalent
Use in AI/AN
infantsCurrently recommended Hib
vaccine for AI/AN infantsCurrently recommended for
general U.S. infants; not yet
preferentially recommended
for AI/AN infants
Hib Antigen and
Conjugate7.5 µg PRP
OMP3.0 µg PRP
OMP
Primary Series 2-dose (2, 4 months) 3-dose (2, 4, 6 months)
Post -dose 1
immunogenicityHigh ???
8PRP: Hib polyribosylribitol  phosphate ; OMP: outer membrane protein of Neisseria meningitidis
HibVax  Study: Primary objective
Do Hib antibody levels in AI/AN infants m eet
non-inferiority  criteria 30 days after dose 1 of
Vaxelis ® compared to PedvaxHIB ®?
9
HibVax  Study Overview
Phase IV, prospective, open label, RCT
2 months
Visit 1
Day 13 months
Visit 2
Day 31
 6 months
Visit 4
Day 1217 months
Visit 5
Day 151
4 months
Visit 3
Day 61
Physical exam
Questionnaire
Receive vaccinesBlood draw
Collection Window30-48 Days
Post Dose 156-90 Days
Post Dose 230-48 Days
Post Dose 3Prior to
Dose 1Safety monitoring
NCT04978818;  JHSPH IRB #11170; Navajo Nation Human Research Review Board #20.374; Alaska Area IRB #2020 -20-01110

HibVax  Study Overview
Phase IV, prospective, open label, RCT
2 months
Visit 1
Day 13 months
Visit 2
Day 31
 6 months
Visit 4
Day 1217 months
Visit 5
Day 151
4 months
Visit 3
Day 61
Physical exam
Questionnaire
Receive vaccinesBlood draw
Collection Window30-48 Days
Post Dose 156-90 Days
Post Dose 230-48 Days
Post Dose 3Prior to
Dose 1Safety monitoring
NCT04978818;  JHSPH IRB #11170; Navajo Nation Human Research Review Board #20.374; Alaska Area IRB #2020 -20-01111

HibVax  Study Overview
Phase IV, prospective, open label, RCT
2 months
Visit 1
Day 13 months
Visit 2
Day 31
 6 months
Visit 4
Day 1217 months
Visit 5
Day 151
4 months
Visit 3
Day 61
Physical exam
Questionnaire
Receive vaccinesBlood draw
Collection Window30-48 Days
Post Dose 156-90 Days
Post Dose 230-48 Days
Post Dose 3Prior to
Dose 1Safety monitoring
NCT04978818;  JHSPH IRB #11170; Navajo Nation Human Research Review Board #20.374; Alaska Area IRB #2020 -20-01112

Inclusion Criteria
•Healthy AI/AN infant born at gestational age of ≥35 weeks
•Between 6 to 12 weeks of age
•Written informed consent provided by parent(s)/Legally
Authorized Representative(s)
Exclusion Criteria (selected)
•Prior receipt of infant vaccines other than birth dose hepatitis B
vaccine
•History of receipt of blood, blood products, or antibody products
•Immunocompromised
•Allergy to any vaccine component, or to latex
•Acute illness and/or fever ≥38.0ºC (time -limited exclusion)
13
Methods
▪Anti -Hib IgG antibody levels measured by commercially available
ELISA assay at CDC/Arctic Investigations Program, Anchorage, AK
▪Geometric mean concentrations (GMCs) assessed using
constrained longitudinal analysis (cLDA)
▪Assumes groups have equal anti -Hib GMC at baseline based on the
randomized study design
▪Results are presented for all evaluable participants complying
with the procedures and intervals between primary doses, as
defined in the protocol
14
Study Enrollment
▪Enrollment began in Jan 2022 in
Anchorage, AK and four sites in the
Navajo Nation (Southwest US)
▪All s tudy visits competed by Oct 2023
Total enrollment 333
Anchorage, AK 26
Chinle , AZ 61
Fort Defiance, AZ 115
Gallup, NM 81
Shiprock, NM 50
15
Study Visit Completion
2 months
Day 1
N3 months
Day 31
N4 months
Day 61
N6 months
Day 121
N7 months
Day 151
N
Completed Visit 333 319 314 300 296
Evaluable Sample 321 307 - 272 270
Evaluable Sample in ATP Cohort 321 298 - 255 245
ATP: According to protocol
No specimens were collected at Day 61, in accordance with the protocol
16
Participant Characteristics
PedvaxHIB ® (N=166) Vaxelis ® (N=167)
Median age in days at Dose 1,
(interquartile range)56 (45 -63) 60 (46 -63)
Male, n (%) 74 (44.6) 84 (50.3)
Site, n (%)
Anchorage, AK 13 (7.8) 13 (7.8)
Chinle, AZ 30 (18.1) 31 (18.6)
Fort Defiance, AZ 57 (34.3) 58 (34.7)
Gallup, NM 40 (24.1) 41 (24.6)
Shiprock, NM 26 (15.7) 24 (14.4)
17
Serious Adverse Events (SAEs)
▪25 SAEs were detected during study follow up in 21 individuals.
▪No SAEs were associated with study participation.
▪The most common SAE was acute respiratory infection (n=21).PedvaxHIB ®
N=166Vaxelis ®
N=167Total
SAEs, n 15 10 25
Participants, n (%) 12 (7%) 9 (5%) 21 (6%)
18
Primary Outcome: Anti -Hib IgG Geometric Mean
Concentration (GMC) 30 Days Post -Dose 1
PedvaxHIB ® Vaxelis ®
Anti -Hib Antibody GMC
µg/mL (95% CI)Observed Data0.39
(0.31 - 0.50)0.41
(0.33 - 0.52)
Modeled by
cLDA0.40
(0.31 - 0.50)0.41
(0.33 - 0.51)
Ratio of GMCs ( Vaxelis  : PedvaxHib )
1.03 (0.75 - 1.41)
The pre -specified non -inferiority criterion was met based on the lower bound of
the 95% confidence interval (CI) around the antibody concentration ratio
[Vaxelis / PedvaxHIB] being > 0.67CI: confidence interval; cLDA : constrained longitudinal data analysis
19
Anti -Hib IgG Geometric Mean Concentration
Day 1 and Day 31
Output from constrained longitudinal data analysis20Putative Correlates of Protection
Long -term
Short -term

Dose 2Dose 3 (Vaxelis Only)Dose 1Anti -Hib IgG Geometric Mean Concentration
Days 1, 31, 121, and 151
Putative Correlates of Protection
Long -term
Short -term
Output from constrained longitudinal data analysis21
020406080100
Day 1 Day 31 Day 121 Day 151ProportionPedvaxHIB
VaxelisProportion with Anti -Hib Concentration ≥0.15 µg/mL
22
020406080100
Day 1 Day 31 Day 121 Day 151ProportionPedvaxHIB
Vaxelis
* χ2 p-value <0.05*Proportion with Anti -Hib Concentration ≥1.0 µg/mL
23
020406080100
Day 31:Day 1 Day 121:Day 1 Day 151:Day 1ProportionPedvaxHIB
VaxelisProportion with 4-fold rise  in Anti -Hib Concentration
from Day 1
24
Limitations
▪Participant follow -up ended at 7 months
▪Over 90% of participants had anti -Hib antibody above the
putative correlate of short -term protection
▪The proportion of participants with anti -Hib antibody
concentrations above the putative correlate of long -term
protection and the anti -Hib GMC were greater in the Vaxelis ®
group
25
Protection Post -Booster
▪Median age of Hib disease in AI/AN children in the
Southwest US: 14 months
▪Majority of cases occur in fully vaccinated children
▪Current booster strategy for AI/AN children: PedvaxHib  at 12 -
15 months
▪Robust immunogenicity seen in heterologous schedules of
PRP -OMP followed by conjugate vaccines with different
carrier proteins (e.g. PRP -TT, HbOC )
Reid et al. , 1993; Decker et al.,  1993; Decker and Edwards, 1998; Greenberg et al., 1995; Wilck et al., 202126
Wilck  MB et al. Vaccine. 2021;39(9):1428 -1434. doi:10.1016/j.vaccine.2021.01.046Significantly
higher
post -booster
anti-Hib GMC
with a
heterologous
booster
dose
Vaxelis +
PRP -TT4 doses
PRP -TT
27
Conclusions
▪Post -dose 1 anti -Hib GMCs following Vaxelis ® met the
pre-specified criteria for non -inferiority.
▪Including Vaxelis ® among the vaccines with a
preferential recommendation would expand the
available options for AI/AN children.
28
Acknowledgements
▪Study participants and their families
▪Institutional Review Boards
▪Navajo Nation Human Research Review Board (NNR -20.374)
▪Fort Defiance Indian Hospital IRB
▪Johns Hopkins Bloomberg School of Public Health IRB (IRB00011170)
▪Alaska Area IRB (2020 -02-011-4)
▪Southcentral Foundation Executive Committee
▪Alaska Native Tribal Health Consortium Human Research Review Committee
▪Indian Health Service, Tséhootsooí  Medical Center, Alaska Native
Medical Center, CDC/Arctic Investigations Program
▪Study Team – Bianca Jackson, Bob Weatherholtz , Scott Zeger , Ros
Singleton, Karen Miernyk , Jonathan Steinberg, James Keck, Study
Nurses, Study Physicians, Regulatory Coordinators, Research
Assistants
29

Summary: The HibVax Study Immunogenicity of H. influenzae type b PRP -OMP  vaccines in American Indian and Alaska Native infants Laura Hammitt, MD Associate Professor, JHSPH Infectious Disease Program Lead, Center for Indigenous Health Johns Hopkins Bloomberg School of Public Health On behalf of the study team in Navajo Nation and Anchorage, Alaska  Disclosures/Disclaimers ▪This study was supported in part by a research grant from the Investigator - Initiated Studies Program of Merck Sharp & Dohme LLC,…


04 Vaxelis Collins 508

Work Group Considerations
Jennifer Collins MD, MSc
Co-Lead, ACIP Hib/Meningococcal Vaccines Work Group
February 29, 2024National Center for Immunization & Respiratory Diseases
Policy question
▪Should Vaxelis (DTaP -IPV-Hib-HepB ) be included with
PedvaxHIB  in the preferential recommendation for
American Indian and Alaska Native infants?
2
3▪574 federally recognized tribes in the United States
–Listening to tribal communities is very important
–CDC’s Office of Tribal Affairs and Strategic Alliances
(OTASA) is helping facilitate
▪ACIP preferential recommendations must be evidence -
basedWork Group Considerations
3
4▪80 attendees, including
–9 from tribes or tribal serving organizations
–46 from Indian Health Service (IHS)
▪Key questions and concerns raised by participants
–Will Vaxelis offer the same protection as PedvaxHIB ?
–Need to monitor for possible breakthrough cases
–Safety and side effectsCDC/NCIRD held a listening session with tribal
communities in January 2024
4 The use of trade names is for identification purposes only and does not imply endorsement by CDC.
Key considerations regarding post -dose 1
immunogenicity of Vaxelis among American
Indian and Alaska Native populations
6Study enrollment included Navajo Nation and
Alaska Native infants
6

7Anti-Hib GMC 30 days post -dose 1 was
non-inferior after Vaxelis vs. PedvaxHIB
7 The use of trade names is for identification purposes only and does not imply endorsement by CDC.

8
GMC differences on day 151 post -dose 1 likely
reflect the 3rd primary series dose of Vaxelis
8 The use of trade names is for identification purposes only and does not imply endorsement by CDC.
9
GMC titers not available beyond day 151 to
assess longer -term protection in this population
9 The use of trade names is for identification purposes only and does not imply endorsement by CDC.
10▪Having a second preferred Hib vaccine option that is a combination vaccine
may improve equity and reliability of vaccine supply
▪Immunologic data are reassuring, however
–Some concern about generalizing to broader AI/AN populations, though
precedent for this with preferential recommendation for PedvaxHIB
–Lack of direct vaccine effectiveness data
–Study did not collect titers beyond infancy re: whether Vaxelis might
better prevent residual cases occurring pre -booster
–Some uncertainty as to why AI/AN populations are particularly affected
by changes in vaccination type; potentially more than just antibody
response?Additional Work Group Considerations
10 The use of trade names is for identification purposes only and does not imply endorsement by CDC.
11▪Including Vaxelis as a second preferred option for AI/AN populations may
improve equity and reliability of vaccine supply
▪Post -dose 1 GMCs of Vaxelis appear non -inferior to that of PedvaxHIB
among Navajo Nation and Alaska Native populations
▪Data gaps
–Studies in broader AI/AN populations
–Short -term efficacy
–Longer -term immunogenicity and efficacy
▪Next steps
–GRADE/ EtR framework to be presented in June
–Plan for vote in JuneFinal reflections and next steps
11 The use of trade names is for identification purposes only and does not imply endorsement by CDC.
Acknowledgments
▪ ACIP Members on the WG
– Jamie Loehr (Interim Chair)
– Wilbur Chen
▪ Ex Officio WG Members
– Margaret Bash (FDA)
– Matthew Clark (IHS)
– Mark Connelly (FDA)
– Francisco Leyva (NIH)
▪ WG Liaisons and Consultants
– Amra Resic  (AAFP)
– Samir Shah (AAP)
– Barb Fluty (ACHA)
– Karyn Lyons (AIM)
– Paul Cieslak (CSTE)
– Kathy Hsu (IDSA)
– Joseline Zafack (NACI)
– Jeff Goad (NFID)
– Jessica Cataldi (PIDS)
– Amy Middleman (SAHM)
– Kathy Poehling (Wake Forest)
– Lynn Bahta (Minnesota Department of Health)
– David Stephens (Emory)▪ CDC Contributors
– Lucy McNamara (DBD/NCIRD)
– Sarah Schillie (DBD/NCIRD)
– LeAnne Fox (DBD/NCIRD)
– Susan Hariri (DBD/NCIRD)
– Amy Rubis (DBD/NCIRD)
– Noele Nelson (DBD/NCIRD)
– Alison Albert (DBD/NCIRD)
– Angela Jiles (DBD/NCIRD)
– Marc Fischer (DIDRI/NCEZID)
– Jonathan Duffy (DHQP/NCEZID)
– Pedro Moro (DHQP/NCEZID)
– Tanya Myers (DHQP/NCEZID)
– Liz Velazquez (ISD/NCIRD)
– Jessica MacNeil (ACIP Secretariat)
– Hannah Rosenblum (ACIP Secretariat)
– Melinda Wharton (ACIP Secretariat)
▪ GRADE/ EtR Support
– Doug Campos -Outcalt (Arizona)
– Rebecca Morgan (Case Western Reserve)
Thank you!
Questions?

Summary: Work Group Considerations Jennifer Collins MD, MSc Co-Lead, ACIP Hib/Meningococcal Vaccines Work Group February 29, 2024National Center for Immunization & Respiratory Diseases Policy question ▪Should Vaxelis (DTaP -IPV-Hib-HepB ) be included with  PedvaxHIB  in the preferential recommendation for  American Indian and Alaska Native infants? 2 3▪574 federally recognized tribes in the United States –Listening to tribal communities is very important –CDC’s Office of Tribal Affairs and Strategic…


01 Meningococcal Poehling 508

ACIP Meningococcal Vaccines Work Group
Introduction
Katherine Poehling, MD, MPH
Chair, ACIP Meningococcal Vaccines Work Group
October 25, 2023National Center for Immunization & Respiratory Diseases
Meningococcal Vaccines Work Group
▪ ACIP Members on the WG
•Katherine Poehling (Chair)
•Lynn Bahta
•Jamie Loehr
▪ Ex Officio WG Members
•Margaret Bash (FDA)
•Mark Connelly (FDA)
•Francisco Leyva (NIH)
▪ WG Liaisons and Consultants
•Amra Resic (AAFP)
•Samir Shah (AAP)
•Sharon McMullen (ACHA)
•Cacky Tate / Karyn Lyons (AIM)
•Paul Cieslak (CSTE)
•Kathy Hsu (IDSA)
•Joseline Zafack (NACI)
•Jeff Goad (NFID)
•Jessica Cataldi (PIDS)
•Amy Middleman (SAHM)
•David Stephens (Emory)▪ CDC Contributors
•Jennifer Collins (DBD/NCIRD)
•Sam Crowe (DBD/NCIRD)
•Lucy McNamara (DBD/NCIRD)
•Ismael Ortega -Sanchez (DVD/NCIRD)
•Andrew Leidner (ISD/NCIRD)
•LeAnne Fox (DBD/NCIRD)
•Susan Hariri (DBD/NCIRD)
•Amy Rubis (DBD/NCIRD)
•Noele Nelson (DBD/NCIRD)
•Alison Albert (DBD/NCIRD)
•Angela Jiles (DBD/NCIRD)
•Jonathan Duffy (DHQP/NCEZID)
•Tanya Myers (DHQP/NCEZID)
•Liz Velazquez (ISD/NCIRD)
•Jessica MacNeil (ACIP Secretariat)
•Melinda Wharton (ACIP Secretariat)
▪ GRADE/EtR Support
•Doug Campos -Outcalt (Arizona)
•Rebecca Morgan (Case Western Reserve)
2
Policy topics under consideration by Work
Group regarding Pfizer’s pentavalent vaccine
▪Should pentavalent vaccine be included as an option for
MenACWY /MenB vaccination in people currently recommended to
receive both vaccines ?
▪Should pentavalent vaccine be included as an option for people currently
recommended to receive MenACWY only ?
▪Should pentavalent vaccine be included as an option for people currently
recommended to receive MenB only ?
3
Summary of ACIP meetings
▪February 2023
–Epidemiology of meningococcal disease in the United States
–Pfizer’s MenABCWY vaccine clinical trials data
–Work group interpretation of Pfizer’s MenABCWY trials data
▪June 2023
–CDC’s cost effectiveness model
–Summary of GRADE and EtRframework
4
Meningococcal Work Group Meeting Review
June─October 2023
▪Feedback from June ACIP meeting
–Review of meningococcal schedule postponed to allow for consideration
of GSK’s forthcoming pentavalent vaccine and availability of data about
post -COVID meningococcal epidemiology
▪Comparisons of cost -effectiveness models
▪Updates on CDC cost -effectiveness model with new price estimate
–Price for pentavalent was ~$40 –90  more than MenB and now is similar
▪Discussed 3 potential recommendation options based on concerns raised by
ACIP members in June and new cost -effectiveness estimates
5
Work Group determinations for policy questions
▪Should the pentavalent vaccine be included as an option for MenACWY /MenB
vaccination in people currently recommended to receive both vaccines ?
•YES (strong consensus)
▪Should the pentavalent vaccine be included as an option for people currently
recommended to receive MenACWY only ?
•NO (strong consensus)
▪Should the pentavalent vaccine be included as an option for people currently
recommended to receive MenB only ?
•Perhaps (limited consensus)
6
Today’s agenda
▪Meningococcal Vaccines Session
▪Later today
–Meningococcal vote regarding Pfizer’s MenABCWY vaccine
–Meningococcal VFC vote regarding Pfizer’s MenABCWY vaccine
7Topic Presenter
Plan for revisiting the adolescent schedule for
meningococcal vaccines Dr. Lucy McNamara (CDC/NCIRD)
Comparison of Pfizer and CDC cost effectiveness
analyses for Pfizer’s MenABCWY vaccineDr. Ismael Ortega -Sanchez (CDC/NCIRD)
Summary of EtRand proposed recommendations for
Pfizer’s MenABCWY vaccineDr. Jennifer Collins (CDC/NCIRD)
Vaccines for Children Resolution Dr. Jeanne Santoli (CDC/NCIRD)

Summary: ACIP Meningococcal Vaccines Work Group  Introduction Katherine Poehling, MD, MPH Chair, ACIP Meningococcal Vaccines Work Group October 25, 2023National Center for Immunization & Respiratory Diseases Meningococcal Vaccines Work Group ▪ ACIP Members on the WG •Katherine Poehling (Chair) •Lynn Bahta •Jamie Loehr ▪ Ex Officio WG Members •Margaret Bash (FDA) •Mark Connelly (FDA) •Francisco Leyva (NIH) ▪ WG Liaisons and Consultants •Amra Resic (AAFP) •Samir Shah (AAP)  •Sharon McMullen (ACHA) •Cacky…


02 Meningococcal McNamara 508

Plan for revisiting the adolescent schedule
for meningococcal vaccines
Lucy McNamara, PhD, MS
Interim Co -Lead, ACIP Meningococcal Vaccines Work Group
October 25, 2023National Center for Immunization & Respiratory Diseases
Considerations for routine schedule discussed
during June 2023 ACIP meeting
▪Strong interest in revisiting the meningococcal vaccine schedule, including
–Whether 11 –12-year old dose is still needed given recent epidemiology
–Revisiting SCDM for B vaccines
•Pentavalent vaccines may complicate the SCDM discussion for providers
•Nuances such as short duration of B protection may be lost in favor of
giving a single injection
▪Opportunity to reduce number of vaccines (i.e., with pentavalent vaccines) is
appealing if maintaining a high level of protection
2
The Meningococcal Vaccines WG plans to
revisit the schedule over the next year to
ensure
▪Adequate time to perform GRADE and EtRassessments
▪Assessment of extended interval data for pentavalent vaccines
▪Integration of any changes into the overall child and adolescent
immunization schedule
▪Assessment of post -COVID epidemiology
3
Proposed key questions
▪Should the MenACWY series recommendations be changed to
–Begin at an older age than currently recommended (11 –12 years)
–Eliminate the 11 –12 year -old dose or change this recommendation to
SCDM?
▪Should the MenB series recommendations be changed to
–Alter the recommended ages or dosing interval to provide better
protection for individuals aged 18 –19  years?
–Revisit the SCDM recommendation for some or all adolescents (e.g.,
those planning to attend college)?
▪Are there ways we can better integrate MenACWY and MenB vaccine
schedules to streamline administration/increase feasibility?
4
Date Topics
Feb 2024 -Terms of reference for schedule change
June 2024-Epidemiology pertinent to possible schedule changes
•Cases/deaths averted by MenACWY dose at 11 –12y
•Meningococcal disease burden stratified by race/ethnicity in adolescents
•Risk factors for serogroup B meningococcal disease among college vs. non -
college students
•Breakthrough meningococcal disease cases in vaccinated individuals
•Extended interval data for pentavalent vaccines
Oct 2024 -GRADE/ EtRfor changes to MenACWY and MenB adolescent schedules
-CE analysis for changes to MenACWY and MenB adolescent schedules
Feb 2025 -VotesTentative timeline for ACIP meetings, 2024 –2025
5
Acknowledgments
▪ ACIP Members on the WG
– Kathy Poehling (Chair)
– Lynn Bahta
– Jamie Loehr
▪ Ex Officio WG Members
– Margaret Bash (FDA)
– Mark Connelly (FDA)
– Francisco Leyva (NIH)
▪ WG Liaisons and Consultants
– Amra Resic (AAFP)
– Samir Shah (AAP)
– Sharon McMullen (ACHA)
– Cacky Tate / Karyn Lyons (AIM)
– Paul Cieslak (CSTE)
– Kathy Hsu (IDSA)
– Joseline Zafack (NACI)
– Jeff Goad (NFID)
– Jessica Cataldi (PIDS)
– Amy Middleman (SAHM)
– David Stephens (Emory)▪ CDC Contributors
– Jennifer Collins (DBD/NCIRD)
– Sam Crowe (DBD/NCIRD)
– Ismael Ortega -Sanchez (DVD/NCIRD)
– Andrew Leidner (ISD/NCIRD)
– LeAnne Fox (DBD/NCIRD)
– Susan Hariri (DBD/NCIRD)
– Amy Rubis (DBD/NCIRD)
– Noele Nelson (DBD/NCIRD)
– Alison Albert (DBD/NCIRD)
– Angela Jiles (DBD/NCIRD)
– Jonathan Duffy (DHQP/NCEZID)
– Tanya Myers (DHQP/NCEZID)
– Liz Velazquez (ISD/NCIRD)
– Jessica MacNeil (ACIP Secretariat)
– Melinda Wharton (ACIP Secretariat)
▪ GRADE/EtR Support
– Doug Campos -Outcalt (Arizona)
– Rebecca Morgan (Case Western Reserve)
6
Thank you!
Questions?

Summary: Plan for revisiting the adolescent schedule  for meningococcal vaccines Lucy McNamara, PhD, MS Interim Co -Lead, ACIP Meningococcal Vaccines Work Group October 25, 2023National Center for Immunization & Respiratory Diseases Considerations for routine schedule discussed  during June 2023 ACIP meeting ▪Strong interest in revisiting the meningococcal vaccine schedule, including –Whether 11 –12-year old dose is still needed given recent epidemiology  –Revisiting SCDM for B vaccines •Pentavalent…


final posted 2025 12 04 7pm 508

MEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)
AGENDA

Thursday, December 4, 2025

8:00 AM    Welcome , Roll Call , and Opening Statement  Dr. Robert Malone
(ACIP Vice Chair)
Dr. Mina Zadeh
(ACIP Executive Secretary, CDC)

8:30 AM     Hepatitis B  – Recap  Dr. Robert Malone
(ACIP Vice Chair)

 Policy Context and Schedule Comparison   Dr. Vicky Pebsworth
(ACIP Childhood and Adolescent
Immunization Schedule Workgroup
Chair)

 Burd en of Disease  Dr. Cynthia Nevison  (Presenter )

 HBV Vaccine Safety  Mr. Mark Blaxill  (CDC )

 Discussion (ACIP members and ex officios)

 Discussion ( Liaisons)

10:40 AM   Hepatitis B Vaccine  Manufacturers     Dr. Candice Robinson (GSK)
Dr. Michelle Goveia (Merck)
Dr. Ayman Chit (Sanofi)

Q&A (ACIP members, ex -officios, liaisons)

11:05 AM   Lunch

11:35 AM    Hepatitis B Vaccines  (continued)

 Summary of the Information and Presentation
of the Vo t e Language  Dr. Vicky Pebsworth
(ACIP  Childhood and Adolescent
Immunization  Schedule  Workgroup
Chair)

 VFC Presentation    Dr. Jeanne Santoli  (CDC )

 CMS Comments     Mr. Andrew Johnson
(CMS , ACIP ex officio )

 Discussion (ACIP members and ex officios)

 Discussion (Liaisons)

1:50 PM
 Perspectives from People with Lived Experience

2:00 PM
 Public Comments

2:30 PM
  Votes    Dr. Robert Malone (ACIP Vice Chair)
 Hepatitis B Vaccine

 Hepatitis B Vaccine - VFC

3:15 PM Coverage Implications

 VFC Comments
 Dr. Georgina Peacock (CDC/NCIRD)
 CMS Comments
 Mr. Andrew Johnson
(CMS , ACIP ex officio )

3:25 PM
 Break

3:30 PM
 Update on Work Groups
 Dr. Robert Malone (ACIP Vice Chair)

3:35 PM Agency Updates  CDC, CMS, FDA, HRSA, IHS, NIH

3:45 PM   Adjourn

Friday December 5, 2025

8:00 AM  Welcome  and Roll Call     Dr. Robert Malone
(ACIP Vice Chair )
Dr. Mina Zadeh
(ACIP Executive Secretary, CDC)

8:20 AM
 Hepatitis B Vaccine Discussion and Votes    Dr. Vicky Pebsworth
(ACIP Childhood and Adolescent
Immunization Schedule
Workgroup Chair)
 Discussion (ACIP members and ex officios)
 Discussion (Liaisons)
 VFC presentation  Dr. Jeanne Santoli (CDC)
 V ote: Hepatitis B Vaccine  Dr. Robert Malone
(ACIP Vice Chair)
 V ote: Hepatitis B Vaccine - VFC

10:20 AM  Break

10:30 AM    Childhood/Adolescent Immunization Schedule
Evolution of the Childhood/Adolescent Vaccination
Schedule in the U.S. and Vaccine Schedule Comparison:
U.S. and other Developed Countries   Mr. Aaron Siri (Presenter)
 Discussion (ACIP members and ex officios)
 Discussion (Liaisons)

12:40 PM  Lunch

1:10 PM
 U.S. vs. Danish Vaccine Schedule    Dr. Tracy Beth Hoeg
(FDA, ACIP ex officio)

 Discussion (ACIP members and ex officios)
 Discussion (Liaisons)

2:30 PM Adjourn

Summary: MEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)     AGENDA         Thursday, December 4, 2025        8:00 AM    Welcome , Roll Call , and Opening Statement  Dr. Robert Malone   (ACIP Vice Chair)       Dr. Mina Zadeh   (ACIP Executive Secretary, CDC)                8:30 AM     Hepatitis B  – Recap  Dr. Robert Malone   (ACIP Vice Chair)           Policy Context and Schedule Comparison   Dr. Vicky Pebsworth    (ACIP Childhood and Adolescent  Immunization Schedule Workgroup …


final posted 2025 12 04 508

MEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)
AGENDA

Thursday, December 4, 2025

8:00 AM    Welcome , Roll Call , and Opening Statement  Dr. Robert Malone
(ACIP Vice Chair)
Dr. Mina Zadeh
(ACIP Executive Secretary, CDC)

8:30 AM     Hepatitis B  – Recap  Dr. Robert Malone
(ACIP Vice Chair)

 Policy Context and Schedule Comparison   Dr. Vicky Pebsworth
(ACIP Childhood and Adolescent
Immunization Schedule Workgroup
Chair)

 Burd en of Disease  Dr. Cynthia Nevison  (Presenter )

 HBV Vaccine Safety  Mr. Mark Blaxill  (CDC )

 Discussion (ACIP members and ex officios)

 Discussion ( Liaisons)

10:40 AM   Hepatitis B Vaccine  Manufacturers     Dr. Candice Robinson (GSK)
Dr. Michelle Goveia (Merck)
Dr. Ayman Chit (Sanofi)
Q&A (ACIP members, ex -officios, liaisons)

11:05 AM   Lunch

11:35 AM    Hepatitis B Vaccines  (continued)
Summary of the Information and Presentation
of the Vo t e Language  Dr. Vicky Pebsworth
(ACIP  Childhood and Adolescent
Immunization  Schedule  Workgroup
Chair)
VFC Presentation   Dr. Jeanne Santoli  (CDC )
CMS Comments    Mr. Andrew Johnson
(CMS , ACIP ex officio )
Discussion (ACIP members and ex officios)
Discussion (Liaisons)
1:50 PM Perspectives from People with Lived Experience
2:00 PM Public Comments
2:30 PM  Votes    Dr. Robert Malone (ACIP Vice Chair)
Hepatitis B Vaccine
Hepatitis B Vaccine - VFC
3:15 PM Coverage Implications
VFC Comments
CMS Comments
3:25 PM  Break
3:30 PM  Update on Work Groups
Dr. Georgina Peacock  (CDC)
Mr. Andrew  Johnson
(CMS , ACIP ex officio )
Dr
. Robert M alone (ACIP Vi ce Chair)
3:35 PM Agency Updates  CDC, CMS, FDA, HRSA, IHS, NIH
3:45 PM  Adjourn
Friday December 5, 2025

8:30 AM     Welcome  and Roll Call     Dr. Robert Malone
(ACIP Vice Chair )
Dr. Mina Zadeh
(ACIP Executive Secretary, CDC)

9:30 AM
  Childhood/Adolescent Immunization Schedule
Evolution of the Childhood/Adolescent Vaccination
Schedule in the U.S. and Vaccine Schedule Comparison:
U.S. and other Developed Countries
     Mr. Aaron Siri  (Presenter )
 Discussio n (ACIP members and ex officios)

 Discussion (Liaisons)

12:05 PM    Lunch

12:35 PM
 U.S. vs. Danish  Vaccine Schedule    Dr. Tracy Beth H oeg
(FDA, ACIP e x officio )

 Discussion (ACIP members and ex officios)

 Discussion (Liaisons)

1:35 PM

 Association Between Aluminum Exposure from
Vaccines Before Age 24 Months and Persistent
Asthma at Age 24 to 59 Months
 Dr. Martin Kulldorff  (HHS )
 Discussion (ACIP members and ex officios)

 Discussion (Liaisons)

2:35 PM     Vaccines and Aluminum  Adjuvants    Dr. Evelyn Griffin  (ACIP Member )

 Discussion (ACIP members and ex officios)

 Discussion (Liaisons)

3:45 PM    Adjourn


draft posted 2025 12 01 508

MEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)
AGENDA - DRAFT

Ce
nters for Disease Control and Prevention
Atlanta, Georgia 30329

Thursd ay, December 4, 2025
8:00 AM  Welcome and Roll Call

 Agency Updates

Hepatitis B Vaccine
 Presentation
 Discussion

 Break

 Hepatitis B Vaccine  (continued)
 Presentation
 Discussion

 Lunch

 Hepatitis B Vaccine  (continued)
 VFC presentation
 CMS presentation
 Discussion

 Public Comments

 Break

 Votes

5:00 PM  Adjourn

MEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)
AGENDA - DRAFT

Cente
rs for Disease Control and Prevention
Atlanta, Georgia 30329

Friday , December 5, 2025
9:00 AM Welcome and Roll Call
 Updates on ACIP Workgroups

 CDC Vaccine Risk Monitoring Evaluation
 Discussion

 Vaccine Schedule History

 Childhood /Adolescent Immunization Schedule
 Discussion

Lunch

 Vaccine  Schedule  Considerations
 Discussion

 Break

 Adjuvants and Contaminant s
 Discussion

5:30 PM  Adjourn

Summary: MEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)   AGENDA - DRAFT     Ce nters for Disease Control and Prevention  Atlanta, Georgia 30329    Thursd ay, December 4, 2025   8:00 AM  Welcome and Roll Call         Agency Updates         Hepatitis B Vaccine     Presentation     Discussion         Break         Hepatitis B Vaccine  (continued)      Presentation     Discussion         Lunch         Hepatitis B Vaccine  (continued)      VFC presentation     CMS presentation    …


draft posted 2025 11 14 508

MEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)
AGENDA - DRAFT

Ce
nters for Disease Control and Prevention
Atlanta, Georgia 30329

Thursday, December 4, 2025
9:00 AM Welcome and Roll Call
 Updates on ACIP Workgroups

 CDC Vaccine Risk Monitoring Evaluation
 Discussion

 Vaccine Schedule History

 Childhood /Adolescent Immunization Schedule
 Discussion

Lunch

 Vaccine  Schedule  Considerations
 Discussion

 Break

 Adjuvants and Contaminant s
 Discussion

5:30 PM  Adjourn

MEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)
AGENDA – DRAFT

C
enters for Disease Control and Prevention
Atlanta, Georgia 30329

Friday, December 5, 2025
8:00 AM  Welcome and Roll Call

 Agency Updates

Hepatitis B Vaccine
 Presentation
 Discussion

 Break

 Hepatitis B Vaccine  (continued)
 Presentation
 Discussion

 Lunch

 Hepatitis B Vaccine  (continued)
 VFC presentation
 CMS presentation
 Discussion

 Public Comments

 Break

 Votes

5:00 PM  Adjourn

Summary: MEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)   AGENDA - DRAFT     Ce nters for Disease Control and Prevention  Atlanta, Georgia 30329    Thursday, December 4, 2025      9:00 AM Welcome and Roll Call     Updates on ACIP Workgroups         CDC Vaccine Risk Monitoring Evaluation     Discussion         Vaccine Schedule History         Childhood /Adolescent Immunization Schedule      Discussion         Lunch         Vaccine  Schedule  Considerations     Discussion        …


final posted 2025 09 19 508

MEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)
Agenda

Centers
 for Disease Control and Prevention
Atlanta, GA

Thursday, September 18, 2025
10:00 AM  Welcome and Roll Call  Dr. Martin Kulldorff (ACIP Chair)
Dr. Mina Zadeh (ACIP Executive Secretary, CDC)
10:30 AM  Update on Work Groups  Dr. Martin Kulldorff (ACIP Chair)

10:40  AM Measles, Mumps, Rubella, and Varicella
(MMRV) Vaccines
 Introduction  Dr. Martin Kulldorff (ACIP Chair)
 Background on MMRV  Dr. Arjun Srinivasan (CDC/NCIRD)
 Presentation on febrile seizure following
MMRV vaccine  Dr. John Su (CDC/NCEZID)
 MMRV  Vaccine Manufacturer Statements  TBD
 Proposed recommendations  and discussion  Dr. Martin Kulldorff (ACIP Chair)
 VFC presentation  Dr. Jeanne Santoli (CDC/NCIRD)

12:35  PM Lunch
1:05 PM Hepatitis B Vaccine
 Introduction  Dr. Martin Kulldorff (ACIP Chair)
 Presentation on Hepatitis B Birth Dose
Vaccination  Dr. Adam Langer (CDC/NCHHSTP)
 Hep B vaccine safety updates  Dr. John Su (CDC/NCEZID)
 Hep B  Vaccine Manufacturer Statements  TBD
 Proposed recommendations and discussion  Dr. Martin Kulldorff (ACIP Chair)
 VFC presentation  Dr. Jeanne Santoli (CDC/NCIRD)

3:55 PM Break

4:10 PM Agency Updates  CDC, CMS, FDA, HRSA, IHS, NIH

4:30 PM  Public Comment

5:00 PM  Votes

MMRV vaccines  Dr. Martin Kulldorff (ACIP Chair)
 MMRV vaccines - VFC  Dr. Jeanne Santoli (CDC/NCIRD)

5:30 PM  Adjourn

MEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)
Agenda

Friday, September 19, 2025
8:30 AM  Welcome and Roll Call  Dr. Martin Kulldorff (ACIP Chair)
Dr. Mina Zadeh (ACIP Executive Secretary, CDC)

8:40 AM  Votes
 Hepatitis B vaccines  Dr. Martin Kulldorff (ACIP Chair)
 Hepatitis B vaccines – VFC  Dr. Jeanne Santoli (CDC/NCIRD)

9:00 AM Agency Updates  CDC, CMS, FDA, HRSA, IHS, NIH

9:10 AM COVID -19 Vaccines
 Introduction  Dr. Retsef Levi (ACIP WG Chair)
 COVID -19 epidemiology update  Dr. Arjun Srinivasan (CDC/NCIRD)
 Updates to 2024 -2025 COVID -19
Implementation Considerations  Dr. Arjun Srinivasan (CDC/NCIRD)
 COVID -19 vaccine effectiveness update  Dr. Arjun Srinivasan (CDC/NCIRD)
 COVID -19 vaccine safety update  Dr. John Su (CDC/NCEZID)

10:10 AM Break

10:15 AM COVID -19 Vaccines (continued)
 Workgroup Safety Uncertainties of mRNA
COVID Vaccines  Dr. Wafik El -Deiry & Dr. Charlotte Kuperwasser
(COVID -19 Workgroup Member)
 Genomics of Vaccine -Induced Myocarditis  Dr. Bruce Carleton (COVID -19 Workgroup Member)
 Economic analysis of COVID -19 vaccination  Dr. Arjun Srinivasan (CDC/NCIRD) on behalf of the
University of Michigan
 COVID -19 Vaccine Manufacturer Statements  TBD

11:25 AM Lunch

11:45 AM  COVID -19 Vaccines (continued)
 COVID -19 Discussion Framing  Dr. Retsef Levi (ACIP WG Chair)
 Presentation on a dditional workgroup
considerations in COVID- 19 vaccination Policy
and practice  Dr. Stanley Perlman, Dr. Henry Bernstein, Dr. Mitchell
Miglis (COVID- 19 Workgroup Members)
 Proposed recommendations and discussion  Dr. Retsef Levi (ACIP WG Chair)

1:45 PM Break

1:50 PM Public Comment

2:20 PM Votes

COVID -19 Vaccines  Dr. Retsef Levi (ACIP WG Chair)

3:00 PM  Adjourn

Acronyms
CDC Centers for Disease Control and Prevention
CMS Centers for Medicare & Medicaid Services
COVID-19 Coronavirus disease 2019
FDA Food and Drug Administration
HRSA Health Resources and Services Administration
IHS Indian Health Service MMRV Measles, Mumps, Rubella, Varicella Vaccine NCIRD National Center for Immunization & Respiratory Diseases
NCEZID National Center for Emerging and Zoonotic Diseases  NCHHSTP National Center for HIV , Viral Hepatitis, STD, and Tuberculosis Prevention NIH National Institutes of Health
VFC Vaccines for Children

Summary: MEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)   Agenda    Centers  for Disease Control and Prevention  Atlanta, GA     Thursday, September 18, 2025      10:00 AM  Welcome and Roll Call  Dr. Martin Kulldorff (ACIP Chair)   Dr. Mina Zadeh (ACIP Executive Secretary, CDC)      10:30 AM  Update on Work Groups  Dr. Martin Kulldorff (ACIP Chair)       10:40  AM Measles, Mumps, Rubella, and Varicella  (MMRV) Vaccines     Introduction  Dr. Martin Kulldorff (ACIP Chair)   …