06 RSV Adult Melgar 508

RSV Vaccination in Adults:
Work Group Interpretations
Michael Melgar, MD
Amadea Britton, MD, SMAdvisory Committee on Immunization PracticesOctober 24, 2024National Center for Immunization and Respiratory Diseases
2•Summarize Work Group interpretations of:
-
-
-Current RSV vaccine safety surveillance data and the balance of estimated benefits and risks
associated with protein subunit* RSV vaccination in adults ages 60 years and older
Coadministration of RSV vaccines with other adult vaccines
Clinical trial evidence on protein subunit RSV vaccination* in immunocompromised adults
•Policy considerations for the adult RSV vaccine programOverview
*GSK’s Arexvy  and Pfizer’s Abrysvo  are protein subunit RSV vaccines. Moderna’s mResvia  is an mRNA RSV vaccine, not a protein
subunit vaccine.
Work Group interpretation of updated RSV vaccine safety
data and the balance of benefits and risks of protein subunit RSV vaccination in adults 60 years and older
4•A small number of GBS cases were observed in clinical trials within 42 days after protein subunit
RSV vaccination (GSK Arexvy , Pfizer Abrysvo ). Due to the small number of cases, it was unclear
whether they represented a genuine association between RSV vaccination and GBS.
•Post -licensure data from 2023 –2024 from the Vaccine Adverse Event Reporting System (VAERS)1,
the Vaccine Safety Datalink (VSD)2, and from the partnership between the Food and Drug
Administration (FDA) and the Centers for Medicare and Medicaid Services (CMS)3,4 suggested, but
could not confirm, an elevated risk of GBS after protein subunit RSV vaccination.
•The current older adult RSV vaccine recommendation is intended to focus the vaccination program on older adults in whom the benefits of vaccination most clearly outweigh the potential risks (all adults aged ≥75 years, adults aged 60 –74 years at increased risk of severe RSV disease).
•To date, there have been no cases of GBS within 42 days after Moderna mResvia  vaccination in
clinical trials; post-licensure safety surveillance for this vaccine began in June 2024 after licensure and data are not yet available.RSV vaccine safety recap as of June 2024 :
Guillain -Barré syndrome (GBS)
1. https://www.cdc.gov/acip/downloads/slides -2024- 02-28-29/05- RSV- Adults -Shimabukuro -508.pdf
2. https://www.cdc.gov/acip/downloads/slides -2024- 06-26-28/05- RSV- Adult -Donahue -508.pdf
3. https://www.cdc.gov/acip/downloads/slides -2024- 02-28-29/06- RSV- Adults -Lloyd --508.pdf
4. https://www.cdc.gov/acip/downloads/slides -2024- 06-26-28/06- RSV- Adult -Lloyd -508.pdf
5As of June 2024:
•~1.3 million protein subunit RSV vaccine doses,
2
8 GBS cases identified through diagnostic codes
•Elevated incidence rate ratio of GBS following both GSK
 Arexvy  and Pfizer Abrysvo  vaccination, but
estimates were not statistically significant
•Data suggested difference in attributable risk by pr
oduct2
-GSK A rexvy : 3 excess cases per 1 million doses (95% CI: -3, 10)
-Pfizer A brysvo : 16 excess cases per 1 million doses (95% CI: 3, 29)

•No data available regarding concomitant v
accinationsUpdate October 2024:
•~3.2 million protein subunit RSV vaccine doses, 9
5 GBS cases identified through diagnostic codes
(24 excluded through medical record review1)
•Elevated incidence rate ratio of GBS following both v
accines; results reached statistical significance for
GSK Arexvy , but not for Pfizer Abrysvo, which had
fewer doses administered
•Attributable GBS risk similar for both products2
-GSK A rexvy : 7 excess cases per 1 million doses (95% CI: 2, 11)
-Pfizer A brysvo : 9 excess cases per 1 million doses (95% CI: 0, 18)
•30–50% of doses were concomitantly administered
with another vaccine; no evidence that concomitant vaccination explains the increase in GBS rate after protein subunit RSV vaccination
1.Brighton Collaboration (BC) case definition for GBS was applied, requiring Level 1 –3  certainty: https://brightoncollaboration.org/guillain -barre -and- miller -fisher -syndromes -2/. Of the
95 initially identified cases, 51 were confirmed through medical record review, 24 were excluded (BC Level 4 –5), and 20 did not have medical record available for review.
2.Residual confounding is possible, and the analysis was not designed to compare risk between the two vaccines. Baseline risk o f GBS ma y impact estimated attributable risk.What have we learned about GBS risk from the FDA-CMS self -controlled
case series analysis since June 2024?
6The Work Group has previously  reviewed examples from other licensed and
recommended vaccines of benefit -risk considerations in practice.
• Seasonal influenza vaccine: routine annual influenza vaccination is recommended for all persons aged ≥6
months who do not have contraindications. Adults aged ≥65 years should preferentially receive high -dose,
recombinant, or adjuvanted influenza vaccines.1
–The data on the association between GBS and seasonal influenza vaccination are variable and
inconsistent across influenza seasons. If there is an increased risk of GBS following influenza vaccination it is small, on the order of 1–2 additional cases per million doses of influenza vaccine
administered. Studies also suggest that it is more likely that a person will get GBS after getting influenza disease than after influenza vaccination.
2
1. Grohskopf LA, et al. Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices — United States, 2023 –24 Influenza Season.
MMWR Recomm  Rep 2023;72(No. RR -2):1 –25. http://dx.doi.org/10.15585/mmwr.rr7202a1
2. Vellozzi  C, Iqbal S, and Broder K. Guillain- Barré Syndrome, Influenza, and Influenza Vaccination: The Epidemiologic Evidence, Clinical Infectious Diseases , Volume 58, Issue 8, 15 April 2014, Pages 1149 –
1155, https://doi.org/10.1093/cid/ciu005 .
7
–
Recombinant zoster vaccine : CDC recommends two doses of recombinant zoster vaccine (RZV, Shingrix) 2–6
months apart for adults aged ≥50 years and for adults aged ≥19 years who are or will be
immunocompromised, for prevention of herpes zoster (shingles) and related complications.3,4
–3–6 additional cases of GBS projected per million RZV vaccinated .5
–Risk-benefit analysis incorporated available data on risk of GBS following zoster disease and vaccination with RZV
3. Dooling KL, et al. Recommendations of the Advisory Committee on Immunization Practices for Use of Herpes Zoster Vaccines. MMW R Morb  Mortal Wkly  Rep 2018;67:103– 108. http://dx.doi.org/10.15585/mmwr.mm6703a5
4. Anderson TC, et al. Use of Recombinant Zoster Vaccine in Immunocompromised Adults Aged ≥19 Years: Recommendations of the Advi sory Committee on Immunization Practices —  United States, 2022. MMWR Morb  Mortal
Wkly  Rep 2022;71:80 –84. http://dx.doi.org/10.15585/mmwr.mm7103a2
5. Janusz CB, et al. Projected risks and health benefits of vaccination against herpes zoster and related complications in US ad ults. Hum Vaccin  Immunother. 2022 Nov 30;18(5):2060668.
https://doi.org/10.1080/21645515.2022.2060668The Work Group also reviewed examples from other licensed and recommended
vaccines of benefit -risk considerations in practice.
8Available data suggest that risk is comparable to, and potentially greater than, that of other
c
urrently licensed and recommended adult vaccines.
No evidence of a difference in risk between protein subunit vaccines1 (GSK, Pfizer).
The Work Group emphasized that risk of GBS associated with protein subunit RSV vaccines1
should be considered in the context of the public health benefits of RSV vaccination.
In June 2024, ACIP reviewed results of a mathematical modeling analysis comparing the n
umbers of RSV- associated hospitalizations, intensive care unit (ICU) admissions, and deaths
avertable per 1 million persons vaccinated vs. the numbers of potential vaccine- attributable
GBS cases.2
This analysis has been updated to account for the most up to date information on protein s
ubunit RSV vaccine effectiveness, duration of protection, and GBS risk1.The Work Group concluded that available data support existence
of increased risk of GBS after protein subunit RSV vaccination1
1.GSK’s A rexvy  and Pfizer’s Abrysvo  are protein subunit RSV vaccines. Moderna’s mResvia  is an mRNA RSV vaccine, NOT a protein subunit vaccine. To date, Moderna’s
mResvia  vaccine has NOT been associated with increased risk of Guillain- Barré syndrome. Post -licensure safety surveillance for mResvia  began recently in June 2024.
2.https://www.cdc.gov/acip/downloads/slides -2024 -06-26-28/09- RSV-Adult- Hutton- 508.pdf
9Same model presented in June 2024, with the following changes:
•Updated attributable risk estimates for GBS as presented earlier this morning
•Updated vaccine effectiveness (VE) assumptions
-Protein subunit RSV vaccination assumed to confer 36 months of protection
(
increased from 24 months)
-Inclusion of preliminary first- s eason VE estimates against RSV-associated
hospitalization from a retrospective cohort study in Medicare beneficiaries aged ≥65 years
1 in the meta -analyses of first- season VE against hospitalization1–4
•Base case evaluates protein subunit RSV vaccination generally, rather than
th
e GSK and Pfizer vaccines individuallyBenefits and risks of protein subunit RSV vaccination
(GSK Arexvy , Pfizer Abrysvo ): methods updates
1. Unpublished results from analysis conducted by the Food and Drug Administration (FDA), Center for Biologics Evaluation and Re se arch (CBER), Office of Biostatistics and Pharmacovigilance (OBPV) in partnership with the Centers
for Medicare and Medicaid Services (CMS). Personal communication with CDC.
2. Surie D, Self WH, Zhu Y, et al. Investigating Respiratory Viruses in the Acutely Ill (IVY) Network. RSV Vaccine Effectiveness  Ag ainst Hospitalization Among US Adults 60 Years and Older. JAMA. 2024 Oct 1;332(13):1105- 1107.
https://pubmed.ncbi.nlm.nih.gov/39230920/
3. Payne AB, Watts JA, Mitchell PK, et al. Respiratory syncytial virus (RSV) vaccine effectiveness against RSV- as sociated hospitalisations and emergency department encounters among adults aged 60 years and older in the USA,
October, 2023, to March, 2024: a test -negative design analysis. The Lancet. 2024;404(10462):1547-1559. https://doi.org/10.1016/S0140- 6736(24)01738-0
4. Unpublished results from the Veterans Health Administration presented in June 2024: https://www.cdc.gov/acip/downloads/slides -2024- 06-26-28/07-RSV- Adult -Surie -508.pdf
10Per 1 Million Persons Vaccinated with Protein Subunit RSV Vaccine :
1.Range of outcomes avertable was calculated using published 95% confidence intervals (outpatient only) and adjusted 95% confid en ce interval of RSV -associated incidence of the outcome observed in RSV -NET
2.FDA self - controlled case series analysis, among CMS Medicare beneficiaries ≥65 years with Parts A, B, and D coverage who did not  have a GBS claim in the 365 days before vaccination. Analysis based on
diagnoses of GBS in inpatient claims data in risk interval (1 –42 days after RSV vaccination) compared to control interval (43 –90 days after RSV vaccination). GBS cases identified using ICD -10 diagnosis of GBS in
primary position of inpatient claims coding with chart verification requiring Brighton Collaboration Level 1 –3 certainty. Estima tes adjusted for outcome-dependent observation time, seasonality, and (when
chart review could not be performed) the positive predictive value of diagnostic codes in identifying chart -confirmed GBS cases.  Analysis includes patients with RSV vaccinations only through January 28, 2024
to allow for 90-day post -vaccination observation and 90% or greater claims data completeness. Claims data through July 13, 2024.
3.Although CMS data were limited to Medicare beneficiaries aged ≥65 years, results are extrapolated here to include adults aged 60 -64 years.
4.Credible range spans the lowest lower bound and highest upper bound of attributable risk estimates for the GSK and Pfizer RSV  v accines.Estimated RSV -Associated Outcomes1 Preventable over 3 RSV Seasons  vs. attributable risk of GBS
estimated from self-controlled case series analysis through FDA -CMS partnership, 42-day risk interval2
0–184 attributable  cases of GBS790 830 5,600
0 1000 2000 3000 4000 5000 6000 7000 8000 9000320 850 3,700
0 1000 2000 3000 4000 5000 6000 7000 8000 9000Adults Aged 60–74 Years3 at Increased
Risk of Severe RSV Disease
(1,700–6,900)
(390–1,580)
(120 –610)Hospitalizations
ICU Admissions
DeathsAd ults Aged ≥75 Years,
General Population
(3,600–8,900)
(520–1,310)
(310–1,450)
Credit: Dr. David Hutton, U. Michigan
11•No statistical signal for GBS in rapid cycle analysis to date.
•As was seen in June 20242, there is a numerical imbalance in the number of GBS cases after
GSK Arexvy  vaccination in adults aged ≥60 years, but the number of cases is small. The
system is currently underpowered to determine whether there is an association with GBS.
•Similarly2, after medical record review, there is a numerical imbalance in the small number
of cases of immune thrombocytopenia (ITP) after GSK Arexvy  vaccination without another
simultaneous vaccine in adults aged ≥60 years, but due to the small number of cases, the
system is currently underpowered to determine whether there is an association with ITP .
•Fewer doses of Pfizer Abrysvo  were administered in VSD, and no conclusions can be drawn
from this system regarding the safety of this vaccine at this time.The Work Group also reviewed updated safety data from the
Vaccine Safety Datalink (VSD) on protein subunit RSV vaccines1.
1.GSK’s Arexvy  and Pfizer’s Abrysvo  are protein subunit RSV vaccines. Moderna’s mResvia  is an mRNA RSV vaccine, NOT a protein subunit vaccine. To date, Moderna’s
mResvia  vaccine has NOT been associated with increased risk of Guillain- Barré syndrome. Post -licensure safety surveillance for mResvia  began recently in June 2024.
2.https://www.cdc.gov/acip/downloads/slides -2024 -06-26-28/05 -RSV -Adult -Donahue-508.pdf
Work Group interpretations on
co-administration of RSV vaccines
with other adult vaccines
13•Co-administration of RSV vaccines and other recommended adult vaccines, in
particular seasonal influenza and COVID- 19 vaccines, is common
•The Work Group was reassured to see these first- ever data from Pfizer
demonstrating that co- administration of protein subunit RSV vaccine, mRNA COVID-
19 vaccine, and high- dose influenza vaccine was safe and generated a non- inferior
humoral immune response
•The Work Group acknowledged the findings of an inferior RSV neutralizing antibody
response with co- administration of Moderna RSV vaccine and high- dose influenza
vaccine, but feels clinical significance of this finding is currently unknown
•These data should also be put in context of a lack of a consistent pattern in combinations of RSV vaccine and other concomitant vaccinations that resulted in inferior immune responsesWork Group interpretations of new co -administration
data
14GSK RSV vaccine Pfizer RSV vaccine Moderna RSV vaccine
Standard dose
influenza vaccineCoadministration non
-inferior No data available Coadministration non- inferior
Adjuvanted
influenza vaccineCoadministration non- inferiority
criteria not met
•RSV titers: non -inferior
•Influenza titers: H3N2 HAI1titers
inferior w/ coadministrationCoadministration non-
inferiorNo data available
High -dose influenza
vaccineCoadministration non- inferior Coadministration non-
inferior2Coadministration non- inferiority
criteria not met•RSV titers: RSV -A and B
neutralizing antibody titers
inferior w/ coadministration
•Influenza titers: non -inferior
mRNA COVID -19
vaccineNo data availableCoadministration non-
inferiorCoadministration non- inferiorSummary of RSV coadministration data with influenza and/or COVID -19 mRNA vaccines in
which non -inferiority of humoral immune response was assessed in older adults
1. HAI: hemagglutination inhibition. Humoral immune response against influenza A/Darwin H3N2 was also assessed post -ho c via microne utralization, which
resulted in a geometric mean titer (GMT) ratio similar to the HAI GMT ratio, with a slightly narrower confidence interval: 1. 23 (95% CI: 1.06 –1.42). Non -inferiority
criteria were not specified for post -hoc analyses. Prespecified non -inferiority criteria for the HAI GMT ratio required that the  95% CI upper bound was <1.50.
2. When given as 3 -wa y coadministration (high -dose influenza vaccine + COVID -19 vaccine + Pfizer RSV vaccine)
15•The Work Group notes our limited understanding of clinical significance of
decreased antibody titers with RSV vaccine co -administration.
•Given the considerable benefits of co -administration and the evidence of
safety of co -administration, the Work Group continues to feel co -
administration is acceptable.1
•In addition, the Work Group looks forward to learning more about Moderna’s analysis on immunologic correlates of protection for RSV as peer -
reviewed methods become available.Work Group interpretations of new co -administration
data (continued)
1.This language is different from CDC’s General Best Practices Guidelines for Immunization, which states that with limited exce ption,
routine administration of all age -appropriate doses of vaccines simultaneously is recommended for persons for whom no specific
contraindications exist at the time of the visit.
Kroger A, Bahta  L, Long S, Sanchez P . General Best Practice Guidelines for Immunization. Best Practices Guidance of the Advisory Committee on
Immunization Practices (ACIP). https://www.cdc.gov/vaccines/hcp/acip -recs/general -recs/index.html . Updated July 22, 2024; accessed October 22, 2024
Work Group interpretations on use of RSV
vaccines in adults with immune compromise
17•During today’s meeting, GSK and Pfizer presented clinical trial data on use of
t
heir RSV vaccines in adults aged ≥18 years with immune compromise.
•These are the first clinical trial results in these populations at high risk of se
vere RSV disease.
•Notably, these trials studied the safety of and the immune response to RSV
v
accination, but did not estimate efficacy against clinical endpoints. First RSV vaccine trials in immunocompromised
persons
18What did we learn from these clinical trials?
GSK Arexvy
•Trial included adults aged ≥18 years with renal or lung
t
ransplant
•One month after a single dose of A rexvy , these
participants had lower RSV neutralizing antibody titers, compared with immunocompetent adults aged ≥50 years
•After a second dose of A
 rexvy  one month after the
first, RSV neutralizing antibody titers increased and were similar to those in immunocompetent adults aged ≥50 years at 2 months post -vaccination
•Measures of cellular immunity after Arexvy
v
accination were similar between
immunocompromised participants and immunocompetent participants
•No specific safety concerns were identified in either clinical trial, though one participant in each trial experienced r
enal transplant rejection after RSV vaccination (judged by investigator to be unrelated to vaccination)
19What did we learn from these clinical trials?
GSK Arexvy
•Trial included adults aged ≥18 years with renal or lung
t
ransplant
•One month after a single dose of A rexvy , these
participants had lower RSV neutralizing antibody titers, compared with immunocompetent adults aged ≥50 years
•After a second dose of A
 rexvy  one month after the
first, RSV neutralizing antibody titers increased and were similar to those in immunocompetent adults aged ≥50 years at 2 months post -vaccination
•Measures of cellular immunity after Arexvy
v
accination were similar between
immunocompromised participants and immunocompetent participantsPfizer Abrysvo
•Trial included adults aged ≥18 years with autoimmune d
isorders on immunomodulator therapy, solid organ
transplant, end- stage renal disease on dialysis, or non-
small cell lung cancer on therapy
•One month after a single dose of Ab rysvo , these
participants had similar RSV neutralizing antibody titers, compared with immunocompetent adults aged ≥60 years from Pfizer’s main phase 3 trial
•The neutralizing antibody response in participants w
ith autoimmune disorders on immunomodulator
therapy and solid organ transplant appeared lower than in adults with end- stage renal disease
•A second dose of Ab
 rysvo  one month after the first did
not appreciably increase neutralizing antibody titers
•No specific safety concerns were identified in either clinical trial, though one participant in each trial experienced r
enal transplant rejection after RSV vaccination (judged by investigator to be unrelated to vaccination)
20•The Work Group was encouraged to see clinical trial data in this population
but would have preferred to see data among adults with the most severe
forms of immune compromise, who are at highest risk of severe RSV disease
(e.g., hematopoietic stem cell transplant, recent lung transplant).
•The Work Group also felt that Pfizer’s inclusion of adults with end -stage
renal disease on dialysis used too broad a definition of immune compromise.
•The Work Group expressed uncertainty in whether neutralizing antibody
titers will correspond to similar clinical efficacy observed in
immunocompetent older adults.
•Absent clinical efficacy data, the Work Group expressed uncertainty in whether 2 doses of GSK’s Arexvy  would be required to result in adequate
protection against severe RSV disease in solid organ transplant recipients.Work Group interpretations
Policy considerations
22•Adults aged ≥75 years should receive a single dose of RSV vaccine
•Adults aged 60– 74 years who are at increased risk of severe RSV disease
should receive a single dose of RSV vaccine
•While uncertainty remains regarding the magnitude of GBS risk associated
with protein subunit RSV vaccination*, the Work Group believes that the
benefits of RSV vaccination outweigh risks among the populations for whom
RSV vaccination is currently recommended.The Work Group affirms that the current older adult
RSV vaccine recommendations are appropriate.
*GSK’s Arexvy  and Pfizer’s Abrysvo  are protein subunit RSV vaccines. Moderna’s mResvia  is an mRNA RSV vaccine, NOT a protein subunit vaccine. To date, Moderna’s
mResvia  vaccine has NOT been associated with increased risk of Guillain -Barré syndrome. Post -licensure safety surveillance for mResvia  began recently in June 2024.
23•The Work Group recognizes several important factors:
-While risk of severe RSV disease increases with age, adults aged <60 years with
certain chronic medical conditions have an elevated risk of severe RSV disease: some may have risk comparable to that in older adults
-Adults from certain racial and ethnic groups may be at increased risk of these conditions at younger ages, compared with White adults
-Conditions that elevate the risk of severe RSV disease may differ by age group; conditions that place adults aged 60– 74 years at increased risk of severe RSV may
not confer the same degree of absolute risk in adults aged 18– 59 years
-Developing RSV vaccine policy in adults <60 years will require careful consideration of the balance of public health benefits and risks in this populationThe Work Group continues to evaluate recommendations for the use
of RSV vaccines in adults aged <60 years, acknowledging there are
now two FDA-approved products for RSV prevention in this age group
24•As was discussed at the June 2024 ACIP meeting, the Work Group felt additional data
on
the potential risk of GBS associated with RSV vaccination were essential prior to
considering RSV vaccine recommendations in adults aged <60 years
•Today we have seen updated results increasing certainty that protein subunit RSV v
accination* is associated with GBS risk, though uncertainty remains regarding the
magnitude of risk
•The Work Group will use these data to continue evaluating risks and benefits, including i
n which groups among adults younger than 60 years the estimated benefits outweigh
the risks
*GSK’s Arexvy  and Pfizer’s Abrysvo  are protein subunit RSV vaccines. Moderna’s mResvia  is an mRNA RSV vaccine, NOT a protein subunit vaccine. To date, Moderna’s
mResvia  vaccine has NOT been associated with increased risk of Guillain- Barré syndrome. Post -licensure safety surveillance for mResvia  began recently in June 2024.The Work Group continues to evaluate recommendations for the use
of RSV vaccines in adults aged <60 years, acknowledging there are
now two FDA-approved products for RSV prevention in this age group
25•Regarding immunocompromised adults, the Work Group recognizes this is a
heterogeneous group who are not all at the same risk of severe RSV disease
•While the data presented today covered a subset of those with immune compromise,
the Work Group does not feel they substantially increase certainty that those with the
most severe forms of immune compromise will benefit from vaccination (e.g., hematopoietic stem cell transplant recipients)
•Therefore, the Work Group did not feel that the data presented today motivated an immediate policy expansion for this group in younger adults, particularly while the FDA-CMS analysis on GBS risk is still ongoingThe Work Group continues to evaluate recommendations for the use
of RSV vaccines in adults aged <60 years, acknowledging there are
now two FDA-approved products for RSV prevention in this age group
26•At least one complete season of safety surveillance data.
-Depending on certainty of findings, additional data may be needed.
•Immunobridging data in adults with immune compromise.
•Data on duration of protection and immune response after re -vaccination.
-The Work Group expressed concern that to date there are no data showing re- vaccination will restore
protection if efficacy wanes over time.
-While restoration of protection with re -vaccination is likely, efficacy in GSK’s pivotal phase III trial did not
improve after re -vaccination at a 12 -month interval.1
-GSK immunogenicity data at 12 - and 24 -month re -vaccination intervals have shown a weaker humoral
immune response, compared with the response after dose 1.2 Pfizer immunogenicity data at a 12 -month re -
vaccination interval has also shown a weaker humoral immune response, compared with the response after
dose 1.3At the June 2024 ACIP meeting the Adult RSV Work Group indicated they
would like to see the following data before moving to vote on an RSV
vaccine recommendation for adults aged <60 years:
1.Ison MG, Papi  A, Athan  E et al. Efficacy and Safety of Respiratory Syncytial Virus (RSV) Prefusion F Protein Vaccine (RSVPreF3 OA) in Older Adults Over 2 RSV  Seasons. Clinical Infectious Diseases. Vol 78(6):1732 -1744. Jan 2024.
2.Gerber, S. Arexvy  (Adjuvanted RSVPreF3) 2 -Year Update. Presented at the Advisory Committee on Immunization Practices meeting, Atlanta, GA; June 26, 2024. https://www.cdc.gov/acip/down loads/slides -2024 -06-26-28/03- RSV-Adult -Gerber -508.pdf.
3. Walsh EE et al. Respiratory Syncytial Virus Prefusion F Vaccination: Antibody Persistence and Revaccination, The Journal of Inf ectious Diseases, The Journal of Infectious Diseases, Vol. 230( 4) Pages e905–e916. Oct. 2024.
https://academic.oup.com/jid/advance -article/doi/10.1093/infdis/jiae185/7644684 .
27•Final results from the FDA - CMS analysis from the first season of RSV
vaccination in Medicare beneficiaries
-The Work Group continues to feel that depending on certainty of findings, additional
da
ta may be needed, and will continue to evaluate other sources of safety data
•Pending certainty in safety findings, data demonstrating vaccine efficacy or
e
ffectiveness against clinical endpoints in the most severely
immunocompromised adults
-While the Work Group appreciates new immunogenicity data, they do not feel these
da
ta are sufficient to support age expansion without final FDA -CMS results on GBS risk
•Immunogenicity data after revaccination with longer time intervals following
in
itial vaccination
-Additional data on longer re -v accination intervals is expected from ongoing
manufacturer clinical trials
 Today  the Work Group continues to feel additional data are necessary before
moving to vote on an RSV vaccine recommendation for adults aged <60 years:
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.

29• Observation Period : August 6, 2023 to March 2, 2024
o Restricted follow up to high -circulation periods after October 1, 2023 with RSV circulation ≥8 cases per 100k beneficiaries
• Outcome : RSV -associated hospitalization identified through International Classification of Diseases, 10th revision, Clinical Modification diagnostic codes
• Covariates :
o Time-fixed covariates in the 365 days prior to index:
Demographic  characteristics (e.g., age, sex, race), socioeconomic status (dual eligibility in Medicare/Medicaid, area deprivation index),  and health conditions (e.g., frailty
score, general medical conditions, immunocompromised status).
Immunocompromised status is determined as a binary covariate based on the presence of immunocompromising diagnoses or treatment
o Time-varying covariates: Census tract -level infection rates
• Statistical Analysis : Marginal Structural Model with Time-Varying Cohorts
o Inverse probability of treatment weighting
o Doubly robust Poisson model with intercepts for the time intervals (weeks) Food and Drug Administration (FDA) RSV vaccine effectiveness analysis among
Community -dwelling Medicare Fee -For-Service (FFS) beneficiaries aged 65 years and
older without dialysis, preliminary results
Number of Eligible
BeneficiariesMedian Age (IQR)Number of
RSV-associated
HospitalizationsPerson-Weeks
(100,000)Median Follow -up
Days Contributed to
CategoryAdjusted VE against
RSV-associated Hospitalization
(95% CI)
Unvaccinated 10,938,075 74 (70, 79) 12,569 2,220.7 126 Reference
Either Product 2,887,152 74 (70, 79) 486 401.8 101 81.8% (80.0%, 83.4%)
GSK RSV Vaccine 1,975,732 74 (70, 79) 352 273.1 100 80.0% (77.8%, 82.1%)
Pfizer RSV Vaccine 911,420 75 (70, 80) 134 128.6 104 84.9% (82.1%, 87.3%)Back up slide not shown at meeting

Summary: RSV Vaccination in Adults: Work Group Interpretations Michael Melgar, MD Amadea Britton, MD, SMAdvisory Committee on Immunization PracticesOctober 24, 2024National Center for Immunization and Respiratory Diseases 2•Summarize Work Group interpretations of: - - -Current RSV vaccine safety surveillance data and the balance of estimated benefits and risks  associated with protein subunit* RSV vaccination in adults ages 60 years and older Coadministration of RSV vaccines with other adult vaccines…


01 IZ Schedules Cineas 508

Recommendations from the Combined Immunization
Schedule Work Group for the 2025 Immunization
Schedules for Children/Adolescents and Adults
Sybil Cineas, MD, FAAP , FACP (ACIP Combined Immunization WG Chair)
Nanda Issa, MD ( CDC Co -Lead )
Patricia Wodi, MD (CDC acting Co -Lead)
ACIP Meeting
October 24, 2024National Center for Immunization and Respiratory Diseases

The Combined Immunization Schedules WG:
•Updates the immunization schedules annually
-Child and adolescent schedule
(for ages 18 years or younger)
-Adult schedule
(for ages 19 years or older)
•Harmonizes the child/adolescent and adult
schedulesCombined Immunization Schedules Work Group
https://www.cdc.gov/vaccines/hcp/imz -schedules/index.html
2
•The immunization schedules are
primarily designed to be a tool for
healthcare providers to ensure
individuals get all the vaccines
they need when they need them. Combined Immunization Schedules Work Group
https://www.cdc.gov/vaccines/hcp/imz -schedules/index.html
3
•The immunization schedules
reflect existing ACIP
recommendations approved by
the CDC director.
-New vaccination policies are not
established in the immunization
schedules.Combined Immunization Schedules Work Group
https://www.cdc.gov/vaccines/hcp/imz -schedules/index.html
4
•ACIP approval of the proposed schedules is necessary prior to publicationReason Topic is Being Presented to ACIP
Child/Adolescent Schedule
onlyBoth Schedules Adult Schedule only
5
Combined Immunization Schedules Work Group
ACIP Members
Sybil Cineas (ACIP WG Chair)
Charlotte Moser
Liaison Representatives
John Epling (AAFP)                         Mary -Margaret Fill (CSTE)
Sarah Coles (AAFP)   Yekatherine  Rasmussen (ACP)
Rhoda Sperling (ACOG)  William Schaffner (NFID)
Holly Fontenot (SAHM)   Robert Hopkins (NFID)
Amy Middleman (SAHM)                         Ken Schmader (AGS)
Sandra Fryhofer (AMA)                             Dana DeShon (NAPNAP)
Sarah McQueen (AAPA)                        Preeti Mehrotra (SHEA)
Marie -Michele Leger (AAPA) Pia Pannaraj (AAP)
Caitlin Newhouse (AIM)                            Kelly Goode ( APhA )Ex Officios
David Kim (OASH)
Susan Farrall (OASH)
Jane Kim (DVA)
Uzo Chukwuma (IHS)
Brittany Rizek (HRSA)
Consultants
Carolyn Bridges
Diane Peterson
Hank Bernstein
Karen Ketner
Kathleen Harriman
Kevin Ault
Litjen Tan
Peter Szilagyi
Susan LettCDC Co -Leads
A. Patricia Wodi
Nanda Issa
6
•ACIP Combined Immunization Work Group — CDC Contributors:Combined Immunization Schedules Work Group
–Akiko Wilson
–Agam Rao
–Andrew Kroger
–Amadea Britton
–David Sugerman
–Dan Filardo
–Daniella Moulia
–Donna Williams
–Emily Cartwright
–Erin Conners
–Femi Adeleke
–Hilda Razzaghi
–Holly Hill
–Jacqueline Tate
–Janell King
–Jefferson Jones –Jennifer Collins
–JoEllen Wolicki
–Joseph Alcober
–Joshua Wong
–Katherine Fleming -Dutra
–Lakshmi Panagiotakopoulos
–Lauren Roper
–Lauri Markowitz
–Lisa Grohskopf
–Liz Velazquez
–Mary Chamberland
–Megan Wallace
–Megan Hofmeister
–Michael Melgar
–Michelle Hughes
–Min Kim–Miwako Kobayashi
–Mona Marin
–Mona Doshani
–Paul Gastanaduy
–Sarah Kidd
–Sarah Schillie
–Susan Goldstein
–Suzanne Johnson -DeLeon
–Tara Anderson
7
•The use of vaccine trade names is for identification purposes only and
does not imply endorsement by the Centers for Disease Control and
Prevention.
•The 2025 immunization schedules presented in the following slides are
drafts and are therefore subject to change based on ACIP’s discussion and
vote.Disclaimer
8
•Harmonization between the child/adolescent and adult schedules
•Edits to all tables
•Content changes of the notes
•Content changes to the appendix listing contraindications and precautions
•Discussion and VoteOutline
9

Summary: Recommendations from the Combined Immunization  Schedule Work Group for the 2025 Immunization  Schedules for Children/Adolescents and Adults  Sybil Cineas, MD, FAAP , FACP (ACIP Combined Immunization WG Chair) Nanda Issa, MD ( CDC Co -Lead ) Patricia Wodi, MD (CDC acting Co -Lead) ACIP Meeting October 24, 2024National Center for Immunization and Respiratory Diseases  The Combined Immunization Schedules WG: •Updates the immunization schedules annually -Child and adolescent schedule  (for ages…


02 IZ Schedules Issa 508

Recommendations from the Combined Immunization
Schedule Work Group for the 2025 Immunization
Schedules for Children/Adolescents and Adults
Sybil Cineas, MD, FAAP , FACP (ACIP Combined Immunization WG Chair)
Nanda Issa, MD (CDC Co -Lead )
Patricia Wodi, MD (CDC acting Co -Lead)
ACIP Meeting
October 24, 2024National Center for Immunization and Respiratory Diseases

Dr. Nanda Issa2025 Update to Child and Adolescent Immunization Schedule
Age 18 years or younger
How to Use the Immunization Schedule
Sections
•Cover Page
•Table 1: Age -based
•Table 2: Catch -up
•Table 3: Medical indication
•Vaccination notes
•Appendix: contraindications
and precautions
•Addendum: updates after
schedule is published
Child and Adolescent Immunization Schedule by Age (Addendum updated June 27, 2024) | Vaccines & Immunizations | CDC
 3
Proposed Update to the 2025 Child/Adolescent Immunization
Schedule
Changes to Tables
•Cover Page
•Table 1
•Table 2
•Table 3Changes to Vaccination Notes
•COVID -19
•DTaP
•Hib
•Influenza
•MMR
•MenB
•Pneumococcal
•RSV monoclonal antibody
•RSV vaccineChanges to Appendix
•MMR/MMRV
•Varicella
1. Use of COVID -19 Vaccines for Persons Aged ≥6 Months: Recommendations of the Advisory Committee on Immunization Practices — Unite d States, 2024 –2025 | MMWR (cdc.gov)
2. Use of Haemophilus influenzae Type b –Containing Vaccines Among American Indian and Alaska Native Infants: Updated Recommendation s of the Advisory Committee on Immunization Practices ― United
States, 2024 | MMWR (cdc.gov)
3. Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practic es — United States, 2024 –25 Influenza Season | MMWR (cdc.gov) 4
Cover page
6
Table 1
Immunization schedule by age group
8
9
10
11
12
Table 2
Catch -up immunization schedule
14
Table 3
Immunization schedule by medical indication
16
17
Notes
Routine vaccination
Persons  NOT  moderately or severely
immunocompromised
• Outlines vaccination series by age
group and COVID -19 vaccination
history.
Special situations
Persons who ARE
moderately or
severely
immunocompromised
•Outlines vaccination
series by age group
and COVID -19
vaccination history.
19
20
21
22
23
Vaxelis  and PedvaxHIB  preferred for
primary series in American Indian
and Alaska native infants.
Guidance for use of Hib in
children receiving early
component complement
inhibitor.
24
25
26
27
28
29
30
31
Appendix
Contraindications and precautions
33
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.Thank you!
Questions?

Summary: Recommendations from the Combined Immunization  Schedule Work Group for the 2025 Immunization  Schedules for Children/Adolescents and Adults  Sybil Cineas, MD, FAAP , FACP (ACIP Combined Immunization WG Chair) Nanda Issa, MD (CDC Co -Lead ) Patricia Wodi, MD (CDC acting Co -Lead) ACIP Meeting October 24, 2024National Center for Immunization and Respiratory Diseases  Dr. Nanda Issa2025 Update to Child and Adolescent Immunization Schedule Age 18 years or younger How to Use the Immunization…


03 IZ Schedules Wodi 508

Recommendations from the Combined Immunization
Schedule Work Group for the 2025 Immunization
Schedules for Children/Adolescents and Adults
Sybil Cineas, MD, FAAP , FACP (ACIP Combined Immunization WG Chair)
Nanda Issa, MD (CDC Co -Lead)
Patricia Wodi, MD (CDC acting Co -Lead)
ACIP Meeting
October 24, 2024National Center for Immunization and Respiratory Diseases

Dr. Patricia Wodi 2025 Update to Adult Immunization Schedule
Age 19 years or older
How to Use the Immunization Schedule
Sections
•Cover Page
•Table 1: Age -based
•Table 2: Medical indication
•Vaccination notes
•Appendix: contraindications
and precautions
•Addendum: updates after
schedule is published
3
Proposed Updates to the 2025 Adult Immunization Schedule
Changes to Tables
•Cover Page
•Table 1
•Table 2Changes to Vaccination Notes
•COVID -19
•Hepatitis B
•Influenza
•Meningococcal
•Mpox
•Pneumococcal
•RSV vaccine
•TdapChanges to Appendix
•Pneumococcal
•Hepatitis B
1. Use of COVID -19 Vaccines for Persons Aged ≥6 Months: Recommendations of the Advisory Committee on Immunization Practices — Unite d States, 2024 –2025 | MMWR (cdc.gov)
2. Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practic es — United States, 2024 –25 Influenza Season | MMWR (cdc.gov)
3. Use of 21 -Valent Pneumococcal Conjugate Vaccine Among U.S. Adults: Recommendations of the Advisory Committee on Immunization Pra ctices — United States, 2024 | MMWR (cdc.gov)
4. Use of Respiratory Syncytial Virus Vaccines in Adults Aged ≥60 Years: Updated Recommendations of the Advisory Committee on Im mun ization Practices — United States, 2024 | MMWR (cdc.gov)4
Cover page
6
7
8
Table 1
Immunization schedule by age group
10
11
12
13
14
15
16
17
18
Table 2
Immunization schedule by medical indication
20
21
22
23
Notes
Routine vaccination
Persons  NOT  moderately or severely
immunocompromised
• Outlines vaccination series by COVID -19
vaccination history.Special situations
Persons who ARE moderately or
severely immunocompromised
•Outlines vaccination series by
COVID -19 vaccination history.
25
26
27
28

29

30

31
Delete
*Note: Heplisav -B and PreHevbrio  are not
recommended in pregnancy due to lack of
safety data in pregnant persons.
32
33
34
35
36
37
38
39
40
41
42
43
44
45
Appendix
Contraindications and precautions
47
Delete
Pregnancy : Heplisav -B and PreHevbrio
are not recommended due to lack of
safety data in pregnant persons. Use
other hepatitis B vaccines if HepB  is
indicated.

48
For more information, contact CDC/ATSDR
1-800-CDC-INFO (232 -4636)
TTY:  1 -888-232-6348    www.cdc.gov           www.atsdr.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 and the Agency for Toxic Substances and Disease Registry.
Thank you!
Questions?
Backup slides
Use of Hepatitis B vaccine during pregnancy(1)
•On September 11, 2024, the FDA announced its approval for a labeling change
for Heplisav -B stating that there is now safety data for its use among pregnant
persons.
•CDC has an update regarding this labeling change in clearance for publication
in MMWR.
–Update recommends, Providers can now vaccinate pregnant persons needing HepB
vaccination with Engerix -B, Recombivax HB, Twinrix, or Heplisav -B.
51
Use of Hepatitis B vaccine during pregnancy(2)
•Prior to September 2024, neither Heplisav -B nor PreHevbrio  had sufficient safety data
among pregnant persons to meet FDA requirements for update to their standardized
package inserts.
–8.1 Pregnancy
Risk Summary
All pregnancies have a risk of birth defect, loss, or other adverse outcomes. In the U.S.
general population, the estimated background risk of major birth defects and miscarriage
in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Data
Human Data: Determination that rates of miscarriage and birth defects are not above
background.
Animal Data:  Data from developmental toxicity studies if they exist.
52
Use of Hepatitis B vaccine during pregnancy(3)
•Recommendations for vaccination of pregnant persons is addressed in the 2018
MMWR: Prevention of Hepatitis B Virus Infection in the United States:
Recommendations of the Advisory Committee on Immunization Practices.
–Guideline lists and describes all vaccines recommended for use in the United States
but makes NO preferential recommendation for use of any particular vaccine.
53

Summary: Recommendations from the Combined Immunization  Schedule Work Group for the 2025 Immunization  Schedules for Children/Adolescents and Adults  Sybil Cineas, MD, FAAP , FACP (ACIP Combined Immunization WG Chair) Nanda Issa, MD (CDC Co -Lead) Patricia Wodi, MD (CDC acting Co -Lead) ACIP Meeting October 24, 2024National Center for Immunization and Respiratory Diseases  Dr. Patricia Wodi 2025 Update to Adult Immunization Schedule Age 19 years or older How to Use the Immunization Schedule Sections…


01 hpv Brooks 508

Introduction to the HPV Vaccines Work Group
Oliver Brooks, MD
Chair, HPV Vaccines Work Group
Advisory Committee on Immunization Practices
October 24, 2024
National Center for Immunization & Respiratory Diseases
•HPV Vaccines Work Group re -formation announced at June 2024
ACIP meeting
•An HPV Vaccines Work Group met previously for many years, but
had been inactive since 2019
•3 meetings since July 2024Background
2
•Routine vaccination
-Age 11 or 12 years
-Can be started at age 9 years
•Catch -up vaccination
-Through age 26 years
•Shared clinical decision -making
-Age 27 –45 yearsCurrent HPV vaccination recommendations,
United States
Recommendations of the Centers for Disease Control and Prevention and the Advisory Committee on Immunization Practices
https://www.cdc.gov/vaccines/hcp/acip -recs/vacc -specific/hpv.html  Number of doses
2 doses  (0, 6 -12 months)
if starting series before 15th birthday
3 doses  (0,1-2, 6 months)
if starting series on or after 15th birthday or if
immunocompromising condition
3
•Number of doses in the recommended HPV vaccination series
-Accumulating evidence on efficacy of HPV vaccination with fewer doses
-In 2022, the World Health Organization recommended a two -dose schedule for
persons aged 9 years or older and, a s an off -label option, a single -dose schedule
can be used for those aged 9 –20 years
-Work Group is reviewing data to inform policy for:
•two doses for persons aged 15 years and older
•one dose for persons aged 9 years and olderWork Group Terms of Reference
4
•Wording of the age for routine HPV vaccination
-Some stakeholders interested in starting vaccination at age 9 years
-Current ACIP recommendations are consistent with vaccination at age 9 years
-Work Group is considering m odification of wording to “ HPV vaccination is routinely
recommended at age 9 to 12 years”  to allow more flexibility Work Group Terms of Reference
5
•Reviewed background data on the two issues being considered
•Number of doses in the recommended HPV vaccination series:
-Started GRADE process
-Planning full Evidence to Recommendations ( EtR) framework and ACIP vote at
future meeting
•Wording of the age for routine HPV vaccination:
-Reviewed related literature
-Not using GRADE
-Planning modified EtR and ACIP vote at future meetingACIP HPV Vaccines Work Group progress
6
ACIP HPV Vaccines Work Group
ACIP voting members
Oliver Brooks (chair)
Noel Brewer
Sybil Cineas
CDC Co -Leads
Carla DeSisto
Lauri MarkowitzLiaison members
Robin O'Meara (AAFP)
Angela Myers (AAP)
Linda Eckert (ACOG)
Alfonso Iorio  (ACP)
Jamilia  Sherls  (AIM)
Sandy Fryhofer (AMA)
Sean O'Leary (IDSA)
Nicole Forbes (NACI)
Kevin Ault (NFID)
Alexandra Yonts  (PIDS)
Nneka Holder (SAHM)
7Ex-Officio members
Sixun Yang (FDA)
Aimée  R. Kreimer (NIH)
Eleanore  Chuang (NIH)
Consultant members
Laura Makaroff (ACS)
Peter Szilagyi
Rachel Winer
Elizabeth Moore (consumer rep)
GRADE consultants
Doug Campos -Outcalt
Rebecca Morgan
Julia Gargano (DVD)
Ruth Stefanos (DVD)
Virginia Senkomago (DCPC)
Patrick Clay (DSTDP)
Harrell Chesson (DSTDP)
Shannon Stokley (ISD)
Adefemi  Adeleke (ISD)
Cassandra Pingali (ISD)ACIP HPV Vaccines Work Group - CDC Staff
Elizabeth R. Unger (DHCPP)
Gitika Panicker (DHCPP)
Christine Olson (ISO)
Julianne Gee (ISO)
Hannah Rosenblum (ACIP Secretariat)
8
Today’s agenda
Introduction to policy consideration:
reduced number of dosesDr. Lauri Markowitz
CDC/NCIRD
Introduction to policy consideration:
wording of the age for routine vaccinationDr. Ruth Stefanos
CDC/NCIRD
Review of literature on HPV vaccination at
ages 9 -10 to increase coverageDr. Sarah Brewer
CDC/NCIRD
Next steps Dr. Carla DeSisto
CDC/NCIRD
9

Summary: Introduction to the HPV Vaccines Work Group Oliver Brooks, MD Chair, HPV Vaccines Work Group Advisory Committee on Immunization Practices October 24, 2024 National Center for Immunization & Respiratory Diseases •HPV Vaccines Work Group re -formation announced at June 2024  ACIP meeting •An HPV Vaccines Work Group met previously for many years, but  had been inactive since 2019 •3 meetings since July 2024Background 2 •Routine vaccination -Age 11 or 12 years  -Can be started at age 9 years …


02 hpv Markowitz 508

Introduction to policy considerations:
Reduced number of HPV vaccine doses
Lauri Markowitz, MD
Co-Lead, HPV Vaccines Work Group
Division of Viral Diseases
Advisory Committee on Immunization Practices
October 24, 2024National Center for Immunization & Respiratory Diseases

▪Brief introduction to human papillomavirus (HPV)
▪HPV vaccines and vaccination recommendations in the United States
▪Overview of data on vaccination with a reduced number of doses
▪World Health Organization recommendations and international landscape Outline
2
Introduction
3
18 years since first HPV vaccine licensure
▪High vaccine efficacy in clinical trials
▪High population impact in real world settings
▪Strong herd effects of vaccination programs
▪Implementation challenges in many countries
▪Lag in vaccine introduction in low - and middle -income counties
4

▪Double -stranded DNA virus (8 kb circular genome)
▪> 200 closely related types
•L1 is major capsid protein
•Sequence of L1 gene determines type
▪12 types classified as high -risk (oncogenic)
•HPV 16 and HPV 18 responsible for most HPV -attributable cancer
▪Low -risk HPV types
•HPV 6 and HPV 11 cause most anogenital warts and recurrent respiratory
papillomatosis
▪Most common sexually transmitted infection
•~ 13 million persons in the United States become infected with a disease -
causing HPV type each year
•Over 90% become undetectable in 2 years Human papillomaviruses
5HPVCervical
Oropha
ryngea l
Anal
PenileVulvarVaginal
HPV-attributable cancer
Wright and Schiffman. N Engl J Med 2003
HPV infection causes cervical cancer (and other cancers)
after years to decades
6
HPV -associated and estimated HPV -attributable cancer
cases per year, United States, 2017 –2021
Cancer siteNumber  of HPV -
associated
cancersPercentage
probably caused
by any HPV typeEstimated number probably caused
by any HPV type*
Female Male Both sexes
Cervix 11,959 91% 10,800 - 10,800
Vagina 898 75% 700 - 700
Vulva 4,418 69% 2,900 - 2,900
Penis 1,381 63% - 900 900
Anus** 7,854 91% 5,000 2,200 7,200
Oropharynx 21,474 70% 2,300 12,900 15,200
TOTAL 47,984 79% 21,800 16,000 37,800
*Estimates were rounded to the nearest 100. Estimated counts might not sum to total because of rounding.
**Includes anal and rectal squamous cell carcinomas
Sources: Cancers Linked With HPV Each Year | Cancer | CDC   and http://www.cdc.gov/cancer/dataviz  7
HPV vaccines and recommendations
8
▪Virus -like particle (VLP) vaccines
▪L1 major capsid proteins self -assemble into VLPs
▪High efficacy with durable protection Available prophylactic HPV vaccines
HPV VLP
9
HPV vaccines licensed in the United States
Vaccine and
brand nameBivalent (2vHPV)
CervarixQuadrivalent (4vHPV)
Gardasil9-valent (9vHPV)
Gardasil 9
Types 16, 18 16, 18, 6, 11 16, 18, 6, 11
31, 33, 45, 52, 58
Prevents cancer cancer
anogenital wartscancer
anogenital warts
Adjuvant AS04
500 µg aluminum hydroxide
50 µg 3-O-desacyl -4’
monophosphoryl lipid AAAHS
225 µg amorphous aluminum
hydroxyphosphate  sulfateAAHS
500 µg amorphous aluminum
hydroxyphosphate  sulfate
Year licensed 2009 2006 2014
Manufacturer GlaxoSmithKline Merck & Co. Merck & Co.
HPV 16 and 18 are oncogenic types that cause most HPV -attributable cancers; HPV 31,33,45,52,58 are oncogenic types that cause ab out 12% of
HPV -attributable cancers; HPV 6,11 cause most anogenital warts and recurrent respiratory papillomatosis 10
HPV vaccines licensed in the United States
Vaccine and
brand nameBivalent (2vHPV)
CervarixQuadrivalent (4vHPV)
Gardasil9-valent (9vHPV)
Gardasil 9
Types 16, 18 16, 18, 6, 11 16, 18, 6, 11
31, 33, 45, 52, 58
Prevents cancer cancer
anogenital wartscancer
anogenital warts
Adjuvant AS04
500 µg aluminum hydroxide
50 µg 3-O-desacyl -4’
monophosphoryl lipid AAAHS
225 µg amorphous aluminum
hydroxyphosphate  sulfateAAHS
500 µg amorphous aluminum
hydroxyphosphate  sulfate
Year licensed 2009 2006 2014
Manufacturer GlaxoSmithKline Merck & Co. Merck & Co.
11After the end of 2016, only 9vHPV available in the United States
Efficacy and immunogenicity trials for initial licensure
of HPV vaccines, 3 -dose schedules (0, 1 -2, 6 months)
Randomized controlled efficacy trials
in ~15 –26-year -old women
Endpoints:
- cervical precancers and external
genital lesions
Per protocol analyses:
- efficacy >96%
- seroconversion ~ 100 %
Immunobridging trials in
9–15-year -olds
Licensure based on non -
inferior antibody response
compared with women in
efficacy trials
Future II Study Group, NEJM 2007; Garland, et al. NEJM 2007; Paavonen, et al. Lancet 2007
  Quadrivalent vaccine trials had other endpoints including, vulvar, vaginal precancers and genital warts12
2006    2011 2016 2019Females
Routine :11or12years ,
can be started at age 9
Catch -up:through 26years
3-dose scheduleMales
Routine :11or12years ,
can be started at age 9
Catch -up:through 21years
3-dose schedule2-dose schedule
iffirst dose  age
<15 yearsShared  clinical  decision -
making : some  adults
27 through  45 years
Catch -up:harmonized
through age 26 yearsEvolution ofHPV vaccination recommendations  –
United States
13
Current HPV vaccination recommendations, United States
Recommendations of the Centers for Disease Control and Prevention and the Advisory Committee on Immunization Practices
https://www.cdc.gov/vaccines/hcp/acip -recs/vacc -specific/hpv.htmlRoutine vaccination
▪Age 11 or 12 years
▪Can be started at age 9 years
  Catch -up vaccination
▪Through age 26 years
  Shared clinical decision -making
▪Age 27 –45 yearsNumber of doses
2 doses  (0, 6 -12 months)
if starting series before 15th birthday
3 doses  (0,1-2, 6 months)
if starting series on or after 15th birthday or
if immunocompromising condition
14
▪Post hoc analyses of a 3 -dose randomized trial (2vHPV vs control vaccine)
-Not all participants completed 3 -dose schedule
-Efficacy against HPV16/18 infection similar after 3, 2, 1 doses
▪Immunobridging trials
-2 doses  in 9–14-year -olds vs 3 doses in young adult women
-Seroconversion and GMTs were non -inferior in 2 -dose groupHow did we get to 2 doses?
15
J Natl Cancer  Inst 2011
GMT ( mMU /mL))Data from 9vHPV
immunobridging  trial
Similar findings for 2vHPV and 4vHPV: Romanowski, Hum Vaccin  Immunother
2016; Puthanakit , JID 2016; Lazcano -Ponce, Vaccine 2014; Dobson, JAMA 2013;
Hernández -Ávila, Hum Vaccin  Immunother  2016; Iversen et al. JAMA 2017HPV type
Iversen  et al. JAMA 20172 doses (0,6 or 0,12 months) in
adolescents (9 -14 years)
    compared with
3 doses (0,2,6 months)
in women (16 -26 years)
16
10100100010000
6 11 16 18 31 33 45 52 58Girls (0,6) Women (0,2,6)
Licensure and recommendations for a 2 -dose HPV
vaccination schedule
Manufacturers  submitted supplemental applications for 2 doses in 9 –14-yr-olds
FDA and other regulatory authorities approved
WHO, ACIP , other advisory groups recommended a 2 -dose series at 9 –14 years
17
2016 2014
Evidence on single -dose  vaccination
18
▪Stimulated by same studies that led to 2 -dose schedules
▪Immunobridging trials not possible for single -dose
-Single dose results in lower antibody titers than 2 or 3 doses
-Basis of protection after HPV vaccination thought to be neutralizing antibody
-No established minimum antibody threshold for protectionSingle -dose  HPV vaccination – initial interest
19

Trial
Girls 12–16 years old
(n=20,300)
Bivalent
(n=10,150)9-valent
(n=10,150)
Active Follow -up
Cervical cells, blood, urine at M12, M18, M24, M30, M36,
M42, M48, M54, M60M0: Randomized to vaccine
M6: Randomized to dosing
schedule
1 Dose 2 Doses 1 Dose 2 DosesEpidemiologic Surveys
(unvaccinated)
HPV infection status
M0 and M6
HPV vaccine
ESCUDDO, Costa Rica (data available 2025)
▪Randomized trial to evaluate non -inferiority of one vs two doses of 2vHPV (Cervarix) and 9vHPV
(Gardasil 9) for prevention of new cervical HPV16/18 infections that persist at least 6 months
▪Evaluate one dose compared to zero doses
ClinicalTrials.gov: NCT03180034
▪Studies that initially provided data had further encouraging data
▪Recognition of a global HPV vaccine supply/demand imbalance
▪Additional studies were planned and conducted
▪Review of data led to revised World Health Organization recommendations
including, “as an off -label option, a single -dose  schedule can be used in girls
and boys aged 9 –20 years.”Single -dose  HPV vaccination – increasing interest
21

Trial/country Evidence VaccineAge ( yrs) at
vaccinationDescription
CVT
Costa RicaEfficacy/
Immunogenicity2vHPV 18–25 Post -hoc analyses
Original trial: randomized to 3 doses or
control, but analyzed as 1 -, 2-, 3-dose groups
IARC -India
IndiaEfficacy/
Immunogenicity4vHPV 10–18 Post -hoc analyses
Original trial: randomized to 2 or 3 doses
but analyzed as 1 -, 2-, 3-dose groups
KEN SHE
KenyaEfficacy 2vHPV
9vHPV15–20 Randomized trial
1 dose 2vHPV, 9vHPV or MCV
DoRIS
TanzaniaImmunogenicity 2vHPV
9vHPV9–14 Randomized trial
1-, 2-, 3-dose groups
22 2vHPV, Cervarix;  9vHPV, Gardasil 9; CVT, Costa Rica Vaccine Trial; IARC, International Agency for Research on CancerTrials with data on single -dose  HPV vaccination
considered by the World Health Organization in 2022
23Costa Rica Vaccine Trial (CVT)
Protection  against prevalent HPV after 2vHPV, through 11 years
Doses Number Prevalent  16/18 HPV
%   (95% CI)Vaccine  efficacy
%   (95% CI)
3 doses 1365 2.0  (1.3–2.8) 80.0%   (70.7 –87.0)
2 doses 62 1.6  (0.1–7.7) 83.8% (19.5 –99.2)
1 dose 112 1.8  (0.3–5.8) 82.1%   (40.2 –97.0)
Unvaccinated 1783 10.0 (8.7 –11.4) Reference▪Post -hoc analysis of RCT: females vaccinated at age 18 –25 years
▪Randomized  to receive 3 doses of 2vHPV or control vaccine
Kreimer AR, et al. J Natl Cancer Inst 2020 23
Costa Rica Vaccine Trial (CVT)
HPV 16 antibody after 1, 2 or 3 doses of 2vHPV, through 11 years
Antibody by VLP -based ELISA at the NCI HPV Immunology Laboratory
Kreimer AR, et al. J Natl Cancer Inst 2020•Stable HPV 16 and 18
antibody levels through 11
years post vaccination with
all dosing schedules
•1 dose levels at least 10 -fold
above level at enrollment
among unvaccinated
Unvaccinated
24
IARC, International Agency for Research on Cancer
Sankaranarayanan  R, et al. Lancet Oncol  2016IARC -India Trial: provides data on immunogenicity
and efficacy of 1, 2 and 3 doses of 4vHPV  (Gardasil)
2 dose
group
25Randomized trial
design lost and
analyzed as
observational
cohortCluster randomized trial
2 vs 3 doses of 4vHPV in 10 –18 year -old
unmarried girls, initiated Sept 2009
Loss of randomization due to order in April 2010 by
Ministry of Health to stop HPV vaccination in research studies2 dose
Group
(0,6 months)3 dose
Group
(0,2,6 months)
251 dose2 doses
0, 2 months3 doses 2 doses
0, >6 months
IARC -India Trial
Protection after 1, 2 or 3 doses of 4vHPV, through 10 years
Doses NumberPersistent HPV16/18 Vaccine efficacy
%   (95% CI)Events %
3 doses 1460 1 0.07 93.3%  (77.5 –99.9 )
2 doses 1452 1 0.07 93.1%  (77.3 –99.8 )
1 dose 2135 1 0.05 95.4%  (85.0 –99.9 )
Control 1260 32 2.54 Reference
26Unvaccinated women age -matched to married vaccinated participants recruited as controls
Persistent infection defined as the same HPV type detected in consecutive samples at least 10 months apart
VE adjusted for background HPV infection frequency, time between date of marriage and first cervical specimen collection, and  number of cervical specimens per participant
26IARC, International Agency for Research on Cancer
Basu P, et al. Lancet Oncol 2021; published correction in Lancet Oncol. 2022 Jan;23(1):e16. IPVC2023 Abstract O177 / #862 . ▪Post hoc analysis of randomized trial: females vaccinated at age 10 –18 years
▪Randomized to receive 2 or 3 doses 4 vHPV
Sexually active females
aged 15 -20 years
2275 randomized
2vHPV
1 dose9vHPV
1 doseMeningococcal
1 dose▪Double -blind, RCT
▪Sexually active females aged 15 -20 years
▪Trial groups
▪2vHPV (Cervarix)
▪9vHPV (Gardasil 9)
▪Meningococcal (d elayed HPV vaccination)
▪Primary objectives
▪Efficacy in preventing incident persistent infection*
–HPV-16/18
–HPV-16/18/31/33/45/52/58 KEN SHE Trial - Kenya
Barnabas R, et al.  NEJM Evidence 2022    *Defined as vaccine -type specific HPV detected at two consecutive time points no less than 4 months apart
 27
KEN SHE: RCT of single -dose  HPV vaccination
Incident persistent 16/18 infections and vaccine efficacy
18 months 36 months
Vaccine NIncident
persistent
HPV 16/18Incidence/
100 PYVE %
(95% CI)Incident
persistent
HPV 16/18Incidence/
100 PYVE %
(95% CI
9vHPV 496 1 0.1797.5%
(81.7 –99.7)1 0.0898.8%
(91.3 –99.8)
2vHPV 489 1 0.1797.5%
(81.6 –99.72 0.1697.5%
(90.0 –99.4)
Meningococcal 473 36 6.83 Reference 72 6.70 Reference▪1458  evaluated f or efficacy  in mITT  cohort
28 Barnabas R, et al. Nature Medicine 2023Enrollment criteria: 1 -5 lifetime partners; HIV negative;  enrollment between December 2018 and June 2021
MCV, meningococcal vaccine;  mITT , modified intention to treat: HPV 16/18 HPV DNA negative (external genital and
cervical swabs) at enrollment and month 3 (self -collected vaginal swab) and HPV antibody negative at enrollment
PY, person years

Barnabas R, et al. NEJM Evidence 2022
Through three years after vaccination , 1-dose HPV vaccine efficacy remained high
Barnabas R, et al. Nature Medicine 20239v VE= 99%  for HPV 16/18 (95% CI: 91 – 100%)
2v VE= 98%  for HPV 16/18 (95% CI: 90 – 99%)
VE=96%  for HPV 16/18/31/33/45/52/58
(95% CI: 89 – 98%)
29KEN SHE: RCT of single -dose  HPV vaccination
DoRIS  - Tanzania
▪Dose Reduction Immunobridging & Safety Study
▪Randomized, open label trial in girls aged 9 -14 years
▪1, 2, 3 doses of 2vHPV (Cervarix)  or 9vHPV (Gardasil 9)
▪Objectives – demonstrate noninferiority
–HPV 16 and 18 antibody response after 1 vs 2 or 3 doses of same vaccine
–HPV 16 and 18 GMCs: 1 dose in DoRIS  vs 1 dose in studies that evaluated efficacy
GMC, geometric mean concentration30Girls aged 9 -14 years
N=930
2vHPV
1 dose2vHPV
2 doses2vHPV
3 doses9vHPV
1 dose9vHPV
2 doses9vHPV
3 doses
DoRIS  conclusions
31
 Watson -Jones D, et al. Lancet Global Health 2022
DoRIS  conclusions
▪Seropositivity >97. 8%after vaccination for all vaccine groups
32 Watson -Jones D, et al. Lancet Global Health 2022
DoRIS  conclusions
▪Seropositivity  >97.8%  after vaccination for all vaccine groups
▪Antibody levels  lower after 1 dose compared with 2 or 3 doses
•Kinetics, with plateau, similar for all doses
33
 Watson -Jones D, et al. Lancet Global Health 2022     9vHPV vaccine groups
DoRIS  conclusions
▪Seropositivity >97. 8%after vaccination for all vaccine groups
▪Antibody levels  lower after 1 dose compared with 2 or 3 doses
•Kinetics, with plateau, similar for all doses
▪ Avidity for each HPV type was similar for 3, 2 and 1 doses for both vaccines
34 Watson -Jones D, et al. Lancet Global Health 2022

DoRIS  conclusions
▪Seropositivity >97.8% after vaccination for all vaccine groups
▪Antibody levels  lower after 1 dose compared with 2 or 3 doses
•Kinetics, with plateau, similar for all doses
▪Avidity for each HPV type was similar for 3, 2 and 1 doses for both vaccines .
▪Immunobridging : 1-dose responses were non -inferior in DoRIS  (9-14 year -olds)
compared with those among women in studies where 1 -dose efficacy observed

35
Lancet Global Health 2024
HPV 16 and 18 antibodies measured by ELISA at Frederick National Laboratory for Cancer Research HPV Immunology Laboratory, USA
Study/
countryEvidence VaccineAge ( yrs) at
vaccinationDescription
HOPE
South AfricaImpact/
Effectiveness2vHPV 15–16 1 dose as catch -up in grade 10. Baseline and cross
sectional prevalence surveys; includes WLWH
Thailand Impact
Thailand   Effectiveness 2vHPV Grade 8
age <15 yrs1 or 2 doses, by province; Baseline and post -
vaccination cross sectional prevalence surveys
HANDS
The GambiaImmunogenicity 9vHPV 4–8, 9–14
15–26Randomized trial of 1 or 2 doses vs
3 doses in 15 –26-year -olds
Primavera
Costa RicaImmunogenicity 2vHPV
9vHPV9–14
18–251 dose
3 doses
PRISMA
Costa  RicaEfficacy 2vHPV
4vHPV
9vHPV18–30 Randomized trial of 1 dose of three different HPV
vaccines vs unvaccinated
ESCUDDO
Costa  RicaEfficacy/
Immunogenicity2vHPV
9vHPV12–16 Randomized trial of 1 vs 2 dosesAdditional studies evaluating single -dose  HPV
vaccination, data forthcoming
36 2vHPV, Cervarix;  9vHPV, Gardasil 9;  WLWH, women living with HIV; RCT, randomized controlled trial. All studies conducted among girls/women
Study/
countryEvidence VaccineAge ( yrs) at
vaccination  Data expected
CVT
Costa  RicaEfficacy/
Immunogenicity2vHPV 12–16 14-, 16- and 20 -year data
IARC -India
India Efficacy/
Immunogenicity4vHPV 10-18 12-year data and further
DoRIS
TanzaniaImmunogenicity 2vHPV
9vHPV9-14 36- and 60 -month dataAdditional data from studies reviewed today
372vHPV, Cervarix;  9vHPV, Gardasil 9
WLWH, women living with HIV; RCT, randomized controlled trial. All studies conducted among girls/women
▪Studies of single -dose  also provide data on a 2 -dose schedule
•Studies with a 2 -dose group (0, 6 months)
–CVT (2vHPV): 18 –25-year -olds
–IARC -India (4vHPV): 10 –18-year -olds
▪Immunogenicity trial of 2 vs 3 doses of 9vHPV*
•U.S. study in 15 –26-year -olds
•Ongoing - interim data published Two HPV vaccine doses for persons aged >15 years
38 *Berenson A, et al. NEJM Evidence 2024
2022 World Health Organization
recommendations and global landscape
WHO recommendations forHPV vaccination
December 2022:
Evidence supports a 2-dose schedule from
age 9years and for allolder agegroups for
which HPV vaccines arelicensed.
Asanoff-label option, asingle -dose
schedule can beused ingirls and boys
aged 9–20years.
40
Date: October  2024 41
Doses -intervalNo. of
countries
1 dose 58
2 doses (12 months) 5
2 doses (6 months 76
Not yet introduced 50
Unknown schedule 5Recommended HPV vaccine schedules in 9‒14 -year -olds,
by country
▪Some of the first countries to change to a routine single -dose  schedule
–England, Ireland, Australia
▪Change from a 3 -dose to a 2 -dose schedule for persons ages >14 years
–Netherlands and Sweden
▪Single -dose  recommendations by regional advisory groups
–PAHO in 2023 and AFRO in 2024Policy changes since updated WHO HPV vaccination
recommendations in 2022
42PAHO Technical Advisory Group recommends countries of the Americas to use single -dose  HPV vaccine schedule | OPS/OMS | Organisation  panaméricaine  de la santé
Africa immunization advisory group urges single -dose  HPV vaccine adoption to advance vaccination efforts | WHO | Regional Office for Africa
▪Longer term efficacy and immunogenicity
▪Protection at sites other than the cervix
▪Efficacy and immunogenicity in males*
▪Efficacy and immunogenicity in immunocompromised persons
▪Efficacy and immunogenicity in older age groupsOutstanding questions for single -dose  vaccination ?
Additional data expected over the next year will
address some of these questions
* Data available from a small immunogenicity trial in 11 –12-year -old girls and boys: Zeng et al. Pediatrics 2023 43
▪Plan to conduct two prospective clinical trials, one in females (16 -26 years)
and one in males (ages 16 -26 years).
▪These randomized, double -blind, multi -year clinical trials will examine the
short and long -term efficacy and immunogenicity of a single -dose  of Gardasil 9
versus the currently approved three -dose regimen.
▪Merck is in discussions with FDA about the protocols and the timeline.
Merck Announces Plans to Conduct Clinical Trials of a Novel Investigational Multi -Valent Human Papillomavirus (HPV)
Vaccine and Single -Dose Regimen for GARDASIL®9 Announcement from Merck, March 2024
44
▪HPV vaccines were first studied and licensed in a 3 -dose schedule in persons
aged 9 –26 years and later in a 2 -dose schedule in persons aged 9 –14 years.
▪Data are available on single -dose  HPV vaccination, including from a RCT with 3
years of follow -up, showing high efficacy against incident persistent infection.
▪Long term follow -up suggests protection for >10 years with a single dose.
▪WHO 2022 updated recommendations: 2 doses for persons aged 9 years and
older, with option for single -dose  HPV vaccination through age 20 years,
except those immunocompromised.
▪Countries are considering new or updated HPV vaccination policy and an
increasing number have recommended single -dose  HPV vaccination.
▪Further data on 1 and 2 doses will be available over the next year. Summary
45

▪Review further evidence
•1- and 2 -dose schedules
•Modeling data
•Other relevant data
▪Evaluate evidence using GRADE and evaluate policy questions using the
Evidence to Recommendations framework
•Should a 1 -dose schedule be recommended in some age groups?
•Should a 2 -dose schedule, instead of a 3 -dose schedule, be recommended in
some age groups older than 9 –14 years?Next steps for ACIP HPV Vaccines Work Group
46
What questions does ACIP have regarding the policy
questions being addressed? Questions for ACIP
47
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.Thank You

Summary: Introduction to policy considerations:  Reduced number of HPV vaccine doses Lauri Markowitz, MD Co-Lead, HPV Vaccines Work Group Division of Viral Diseases Advisory Committee on Immunization Practices October 24, 2024National Center for Immunization & Respiratory Diseases  ▪Brief introduction to human papillomavirus (HPV) ▪HPV vaccines and vaccination recommendations in the United States ▪Overview of data on vaccination with a reduced number of doses  ▪World Health Organization recommendations…


03 hpv Stefanos 508

Introduction to policy consideration:
Wording of the age for routine vaccination
Ruth Stefanos, MD, MPH
LCDR, US Public Health Service
Division of Viral Diseases
Advisory Committee on Immunization Practices
October 24, 2024National Center for Immunization and Respiratory Diseases
1
Outline
•Current recommendation and historical context
•Clinical Decision Support for Immunization project
•Vaccination coverage
•Interest in vaccination at age 9 years
2
Current Recommendation
https://www.cdc.gov/acip -recs/hcp/vaccine -specific/hpv.html•HPV vaccination is routinely recommended at age 11 or 12 years
•Vaccination can be given starting at age 9 years
•Since 2006 (first ACIP recommendation), the wording of age at HPV
vaccination initiation has not substantially changed
3
1996 “This report presents a new strategy to improve the delivery of vaccination services to
adolescents and to integrate recommendations for vaccination with other preventive
services provided to adolescents. This new strategy emphasizes vaccination of adolescents
11-12 years of age by establishing a routine visit to their health -care providers.”
Immunization of adolescents. MMWR Recomm Rep. 1996;45(RR -13):1 -16.
2005 “The preferred age for Tdap vaccination is 11 –12 years”
Broder KR, Cortese MM, Iskander JK, et al. MMWR Recomm Rep. 2006;55(RR -3):1-34.
"Introducing a recommendation for MCV4 vaccination among young adolescents might
strengthen the role of the preadolescent visit and have a positive effect on vaccine coverage
among adolescents.”
Bilukha OO, Rosenstein N. MMWR Recomm Rep. 2005;54(RR -7):1-21.
2006 “ACIP recommends routine vaccination of females aged 11 –12 years with 3 doses of
quadrivalent HPV vaccine. The vaccination series can be started as young as age 9 years.”
Markowitz LE, Dunne EF, Saraiya M, et al. MMWR Recomm Rep. 2007;56(RR -2):1-24.Adolescent Platform
Adolescent
Platform
Tdap
MCV4
HPV
4
https://www.cdc.gov/hpv/hcp/vaccination -considerations/boost -rates.htmlAdolescent Platform
5
Current HPV Vaccination Recommendations
https://www.cdc.gov/acip -recs/hcp/vaccine -specific/hpv.htmlRoutine VaccinationAge 11–12 years,
can be started at age 9 years
Catch -Up VaccinationAge 13–26 years,
if not adequately vaccinated
Shared Clinical Decision -MakingSome adults age 27–45 years,
if not adequately vaccinated
Special situation:
History of sexual abuse or assault: Start at age 9 years
6
Notes and full schedule available at: https://www.cdc.gov/vaccines/hcp/imz -schedules/child -adolescent -age.htmlVaccine Birth 1
mo2
mos4
mos6
mos9
mos12
mos15
mos18
mos19–
23
mos2–3
yrs4–6
yrs7–10 yrs 11–
12
yrs13–
15
yrs16
yrs17–
18
yrs
HPVSee
notes
Range of
recommended
ages for all
childrenRange of
recommended
ages for catch -
up vaccinationRange of
recommended
ages for
certain high -
risk groupsRecommended
vaccination can
begin in this age
groupRepresentation of HPV Vaccination Recommendations
on Child and Adolescent I mmunization Schedule
7
Recommended Immunizations for Children 7‒18 Years Old
Parent -Friendly Schedule
https://www.cdc.gov/vaccines/imz -schedules/adolescent -easyread.html8

Clinical Decision Support for Immunization (CDSi)
•Logic for applying ACIP rules to CDS
engines
•For HPV vaccine:
•Minimum age: 9 years
•Earliest recommended age: 11 years
•Prompt for HPV vaccination occurs at
earliest recommended age (11 years)
9https://www.cdc.gov/iis/cdsi/
Estimated Vaccination Coverage, Adolescents Aged 13 –17 Years,
National Immunization Survey -Teen, United States, 2006 –2023
Pingali et al. MMWR  2024    UTD: up -to-date0102030405060708090100
2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023Percent Vaccinated
Survey Year≥1 HPV (females, 79%)
≥1 HPV (males, 75%)
HPV UTD (females, 64%)
HPV UTD (males, 59%)≥1 Tdap
≥1 MenACWYHPV vaccination
recommendation
for malesHPV vaccination
recommendation
for females
10
American Academy of Pediatrics Recommendations
•Beginning in the 2018 –2021 Redbook, HPV vaccination recommendation language
was modified.

“The AAP recommends starting the series between 9 and 12 years, at an age that the
pediatric health care professional deems optimal for acceptance and completion of
the vaccination series.”
American Academy of Pediatrics. Red Book: 2024 -2027 Report of the Committee on Infectious Diseases (33rd Edition)11
Interest in V accination at Age 9
https://www.tandfonline.com/journals/khvi20/collections/HPV -vaccination -starting -age-912
Policy Question
Should the ACIP recommendations state:
HPV vaccination is routinely recommended at age 9 –12 years
  instead of
HPV vaccination is routinely recommended at age 11 or 12 years;
vaccination can be given starting at age 9 years
13
ACIP HPV Vaccines Work Group Next Steps
•Review literature
-Systematic review (completed by CDC)
-Will be presented today
•Review other data
-NIS-Teen
-Randomized Controlled Trial (f inal data not available until 2026)
•Conduct modified Evidence to Recommendations (EtR)
14
15•4 countries: begin at age 9 years
•6 countries: begin at age 10 years
•20 countries: begin at age ≥11 years
•UK: age 12 –13 years
9 10 11 12 13 14 15 16 17 18
Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
SwedenCountry Age (years)
graph adapted from https://vaccine -schedule.ecdc.europa.eu/Scheduler/ByDisease?SelectedDiseaseId=38&SelectedCountryIdByDisease= -1
https://www.gov.uk/government/publications/hpv -universal -vaccination -guidance -for-health -professionals/hpv -vaccination -guidance -for-healthcare -practitioners
Policy Question
Should the ACIP recommendations state:
HPV vaccination is routinely recommended at age 9 –12 years
  instead of
HPV vaccination is routinely recommended at age 11 or 12 years;
vaccination can be given starting at age 9 years
16
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.
Acknowledgments
Sarah Brewer, PhD, MPH
Carla DeSisto, PhD, MPH
Julia Gargano, PhD
Lauri Markowitz, MD
17

Summary: Introduction to policy consideration:  Wording of the age for routine vaccination Ruth Stefanos, MD, MPH LCDR, US Public Health Service Division of Viral Diseases Advisory Committee on Immunization Practices October 24, 2024National Center for Immunization and Respiratory Diseases 1 Outline •Current recommendation and historical context •Clinical Decision Support for Immunization project •Vaccination coverage •Interest in vaccination at age 9 years 2 Current Recommendation…


04 hpv Brewer 508

Human papillomavirus vaccination at age 9 or 10 years
to increase coverage – a systematic review and
narrative review of the literature
Sarah Brewer, PhD, MPH
Division of Viral Diseases
Advisory Committee on Immunization Practices
October 24, 2024 National Center for Immunization & Respiratory Diseases

Background
2
•Since HPV vaccine was first licensed and recommended in 2006 for females, the wording of the
routine age recommendation has remained the same
•While HPV vaccination coverage has increased since HPV vaccination was first recommended,
uptake continues to be lower than other vaccines recommended in adolescence
•There have been many efforts to increase HPV vaccination in the United States
•In the past few years there has been increasing enthusiasm for HPV vaccine initiation at age 9
years to increase coverage Background
3
•Critically evaluate publications investigating HPV vaccination at age 9 –10 years
-Systematic review and narrative summary of literature
-Describe methodologies used
-Provide data summaries and interpretationsObjective
4
Selection criteria
•Dates and location: 2014 –2024, United States
•Population:
-Individuals ≥9 years of age who are eligible to receive HPV vaccination
-Parents/caregivers of persons ≥9 years of age
-Clinicians, providers, or other clinical staff who administer the HPV vaccine
•Evaluation:
-HPV vaccination at ages 9 –10 years
•Outcomes:
-HPV vaccine initiation
-HPV vaccine series completion
-Acceptability among providers and caregivers of routine HPV vaccination at ages 9 –10 years
-Feasibility of routine HPV vaccination at ages 9 –10 years where HPV vaccination is offered
5
PRISMA flow chart for study inclusion in systematic review
6

Study descriptionsStudy Completion Initiation Provider
perspectives/behaviorCaregiver
perspectives
Kajtezovic  2023 X
Saxena 2023 X
St. Sauver 2016 X
Goodman 2023 X
Minihan  2023 X
Hirth  2024 X
Bednarczyk  2023 X
Liu 2016 X
Inguva  2020 X
Kashani  2019 X
Donahue 2015 X
Perkins 2020 X X
Zorn 2022 X X
Goleman 2018 X
Cox 2022 X X
O’Leary 2023 X X
Casey 2022 X X
Huang 2023 X X
Christensen 2023 X
Strasel 2023 X
Isher -Witt 2023 X
Brodie 2018 X
Bowden 2017 X
Kong 2022 X
Biancarelli 2020 X
Vielot 2023 X
Lake 2023 X
Kahn 2023 X
Kohler 2023 X
Aragones 2022 XRetrospective cohort/
observational coverage
studies
Quality
improvement/intervention
coverage projects
Provider/caregiver
behavior and perspectives
7
Retrospective cohort/observational studies (N=11)
Study Completion Initiation Provider
perspectives
/behaviorCaregiver
perspectives
Goodman X
Minihan X
Bednarczyk X
Hirth X
Kajtexovic X
Saxena X
Liu X
St. Sauver X
Inguva X
Kashani X
Donahue XNIS-Teen
Marketscan
Other
8
9 explored impact of initiation at age 9 –10 vs. age ≥11 years on completion or up -to-date
status of the vaccination series
-Many looked at series completion by age 13, but others evaluated up -to-date status at older ages
or used an outcome defined by time to complete the series after receiving first dose
-All but one found higher on time completion of the HPV vaccination series when initiated at ages
9–10 years
-1 also assessed impact of age at initiation on association between race/ethnicity and series
completion; increased odds of series completion across all racial/ethnic groups when initiating at
age 9 –10 years compared to age 12 years
1 assessed association of initiation timing in relation to other routine adolescent vaccines
on series completion
-HPV vaccine series completion higher if HPV vaccination initiated before Tdap or meningococcal
1 investigated predictors of initiation for children aged 9 –13
-The same characteristics were associated with initiation, regardless of age at initiationSummary: retrospective cohort/observational studies
(N=11)
9
Interpretation: retrospective cohort/observational
studies (N=11)
10 *Some studies evaluated completion, but not by age 13 yearsHigher vaccination series completion* when initiating at age 9 –10 vs. 11 –12,
but study limitations preclude a cause -and-effect interpretation
A small percentage of vaccinated adolescents had initiated at age 9 –10 in
most studies (2 –8%)
No information on reasons for initiation at age 9 –10; may have been
differences in those initiating at age 9 –10 vs. 11 –12
There may be differences between providers vaccinating at age 9 –10 and
those vaccinating at age 11 –12
Quality improvement/intervention (N=12)
Study Completion Initiation Provider
perspectives
/behaviorCaregiver
perspectives
Perkins X X
Zorn X X
Goleman X
Cox X X
O’Leary X X
Casey X X
Huang X X
Christensen X
Strasel X
Isher -Witt X
Brodie X
Bowden X
11
All 12 studies evaluated initiation:
-Interventions were multipronged, with one component focused on initiation at ages 9 –10 years
-All studies observed an increase in initiation for all ages at initiation (9 –10 years and ≥11 years),
or at a clinic population level
•Magnitude of increases varied across age groups
•Increases were not sustained in all studies
•Initiation rates at 9 –10 years still lower than initiation at ≥11 years
6 Studies evaluated initiation and completion:
-Increases in completion rates observed in the majority of studiesSummary: quality improvement/intervention studies
(N=12)
12
Quality improvement/intervention (N=12)
N=6 Focus on initiation  only
Author EMR
changeProvider/
staff
trainingPatient
educationQI team/
data
feedbackClinic
incentivesStanding
ordersPatient
reminders
Goleman x x x x
Isher -Witt x x x x
Strasel x x
Christensen x*
Brodie x x
Bowden x x x x
*Analysis attempted to measure association with change in electronic medical record (EMR) only, but there may have been other  undocumented
concurrent events that influenced HPV initiations that were not incorporated into the model
13
Quality improvement/intervention (N=12)
N=6 Focus on both initiation  and completion
Author EMR
changeProvider
/staff
trainingPatient
educationQI team/
data
feedbackClinic
incentivesStanding
ordersPatient
reminders
Perkins x x x x x
Casey x x x x x
Zorn x x x
Cox x x x x x x x
Huang x x x x
O’Leary x x
14
In the majority of QI/Intervention studies, there were increases
in initiation and completion; however:
•Due to multi -pronged interventions, it is unclear if the component focused on
initiation at ages 9 –10 was responsible for any of the increase in coverage
•Within the QI/Intervention studies, vaccination at age 9 was feasible, but not
necessarily better than at ages 11 –12Interpretation: quality improvement/intervention
studies (N=12)
15
Provider/caregiver perspectives and behavior studies
Study Completion Initiation Provider
perspectives/
behaviorCaregiver
perspectives
Vielot X
Biancarelli X
Kong X
Lake X
Kahn X
Kohler X
Aragones XInterviews:
Providers
Surveys:
Providers
Interview/
Survey:
Caregivers
16
2 Clinician Interviews :
-1 intervention study: providers reported a positive experience with recommending vaccination at age 9–10
-1 qualitative study: providers had mixed opinions
3 Clinician Surveys :
-1 survey: among not currently recommending at age 9, family medicine physicians were more willing to
recommend the vaccine at ages 9 –10
-1 survey: strong recommendation differed by age group and specialty
-1 survey: recommendation framing mattered when initiating at ages 9 –10
-Perceived benefits of vaccination varied by initiation age
2 Caregiver Studies:
-Few caregivers reported receiving information or recommendations to vaccinate children before age 11
-Most reported willingness to vaccinate at ages 9 –10Summary: provider/caregiver behavior and perspective
studies (N=7)
17
Interpretation: provider/caregiver behavior and
perspective studies (N=7)
18In limited settings, and mostly small studies, vaccination at ages 9 –10
years was acceptable by caregivers and providers
•We conducted a systematic review evaluating HPV vaccination at ages 9 –10 years
•Data from 30 studies published 2014 –2024 were summarized in a narrative review
•3 general types of studies
-Within retrospective cohort studies, HPV vaccine initiation at ages 9 –10 years was associated with higher
completion by age 13; this was a small proportion of initiators in all studies
•There could  have been meaningful differences between children initiating at ages 9 –10 vs 11 –12
or providers vaccinating at ages 9 –10 vs those vaccinating at the routine age
-Within  QI/ intervention studies findings show vaccination  at age 9  was feasible , but not necessarily better
•Due to the multifaceted approaches; contribution of the recommendation for initiation at age 9 –
10 years on increases in coverage is unclear
-Vaccination at ages 9 –10 years may be acceptable to caregivers and providersOverall summary
19
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.
Acknowledgements
Ruth Stefanos
Lauri Markowitz
Shannon Stokley
Neil C. Murthy
Amimah Asif
21Kajtezovic , S., et al. (2023). "Optimizing timing of adolescent vaccines: Impact of initiating HPV vaccination before Tdap or meningoco ccal vaccination
on timely completion of the HPV vaccine series." Hum Vaccin  Immunother . 19(1): 2175541.

Saxena, K., et al. (2023). "HPV vaccine initiation at 9 or 10 years of age and better series completion by age 13 among priva tely and publicly insured
children in the US." Hum Vaccin  Immunother . 19(1): 2161253.

St. Sauver, J. L., et al. (2016). "Younger age at initiation of the human papillomavirus (HPV) vaccination series is associat ed with higher rates of on -time
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Minihan , A. K., et al. (2023). "The association of initiating HPV vaccination at ages 9 –10 years and up -to-date status among adolescent s ages 13 –17
years, 2016 -2020." Hum Vaccin  Immunother . 19(1): 2175555.

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22Perkins, R. B., et al. (2020). "Improving HPV vaccination rates: a stepped -wedge randomized trial." Pediatrics  146(1).

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23Kong, W. Y., et al. (2022). "Recommending human papillomavirus vaccination at age 9: a national survey of primary care profes sionals." Acad  Pediatr .
22(4): 573 -580.

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Vielot, N. A., et al. (2023). "Acceptability and readiness to promote human papillomavirus vaccination at ages 9 –10 years: a fea sibility study among North
Carolina clinics." Pilot Feasibility Stud.  9(1): 153.

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19(1): 2172276.

Kohler, R. E., et al. (2023). "Mothers’ perceptions and attitudes about HPV vaccination initiation among 9 - and 10 -year -olds." Hum Vaccin  Immunother .
19(3): 2270842.

Aragones, A., Gany , F., Kaplan, A., & Bruno, D. (2022). An opportunity to increase human papillomavirus vaccination rates: Change the guideline s. Hum
Vaccin  Immunother ., 18(6), 2136444. https://doi.org/10.1080/21645515.2022.2136444 References – Provider/caregiver behavior and perspectives studies

Summary: Human papillomavirus vaccination at age 9 or 10 years  to increase coverage – a systematic review and  narrative review of the literature  Sarah Brewer, PhD, MPH Division of Viral Diseases Advisory Committee on Immunization Practices October 24, 2024 National Center for Immunization & Respiratory Diseases  Background 2 •Since HPV vaccine was first licensed and recommended in 2006 for females, the wording of the  routine age recommendation has remained the same •While HPV vaccination coverage…


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HPV Vaccines Work Group – Next Steps
Carla L. DeSisto, PhD, MPH
Co-Lead, HPV Vaccines Work Group
Advisory Committee on Immunization Practices
October 24, 2024
National Center for Immunization & Respiratory Diseases
•Number of doses in the recommended HPV vaccination series:
-Started GRADE process, planning full Evidence to Recommendations ( EtR) framework
-February 2025 ACIP meeting: plan to share additional data from trials/studies,
modeling, and partial EtR
•Wording of the age for routine HPV vaccination:
-Reviewed related literature
-Not using GRADE, planning modified EtR
-February 2025 ACIP meeting: plan to share partial EtR
•Plan for ACIP vote: both issues at the same meeting (not February 2025)ACIP HPV Vaccines Work Group next steps
2
What questions does ACIP have regarding the policy questions to be
addressed?Questions for ACIP

Summary: HPV Vaccines Work Group – Next Steps Carla L. DeSisto, PhD, MPH Co-Lead, HPV Vaccines Work Group Advisory Committee on Immunization Practices October 24, 2024 National Center for Immunization & Respiratory Diseases •Number of doses in the recommended HPV vaccination series: -Started GRADE process, planning full Evidence to Recommendations ( EtR) framework -February 2025 ACIP meeting: plan to share additional data from trials/studies,  modeling, and partial EtR •Wording of the age for routine…


01 cmv Jamieson 508

Summary: ACIP material — 7 pages. CDC vaccine advisory committee document. Open the PDF to read.