12 RSV Adult Melgar 508

1
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.
ACIP Adult RSV Work Group Clinical Considerations
Respiratory Syncytial Virus (RSV) in Adults 60 and older
Michael Melgar, MD
Amadea Britton, MD
Co-Leads, Adult RSV Vaccine Work Group
Coronavirus and Other Respiratory Viruses Division (CORVD)
Advisory Committee on Immunization Practices (ACIP)
June 26, 2024
2▪Transition from the current shared clinical decision -making recommendation
▪Adults aged 60 –74 years at increased risk of severe RSV disease
▪Timing of RSV vaccination for the 2024 –2025 RSV season
▪Coadministration of RSV vaccines with other vaccinesOverview
3
Transition from the current shared clinical
decision -making (SCDM) recommendation
4▪All adults aged 75 years and older should receive a single
dose of RSV vaccination .
▪All adults aged 60–74 years with certain chronic medical
conditions or other factors that increase risk of severe RSV
disease should receive a single dose of RSV vaccination .
▪These recommendations would replace the SCDM
recommendation, meaning that adults aged 60 –74 years
without risk factors for severe RSV disease, are no longer
recommended to receive RSV vaccination. Work Group recommends a transition away from shared
clinical decision -making (SCDM). What does this mean?
5
Adults aged 60 –74 years at increased
risk of severe RSV disease
6Chronic medical conditions associated with increased
risk of severe RSV disease
Lung disease
Cardiovascular disease
Moderate or severe  immune compromise
Diabetes Mellitus with end -organ damage
Other chronic medical conditions that a
healthcare provider determines increases risk
of severe disease due to respiratory infection Neurologic or neuromuscular conditions
Chronic kidney disease, advanced
Hematologic disorders
Liver disorders
6Severe  obesity
(body mass index ≥40 kg/m2)

7Other chronic medical conditions that a
healthcare provider determines increases risk
of severe disease due to respiratory infection While recommendation is intended to be broad enough to implement, note that less
severe stages of Diabetes mellitus, Obesity, and Chronic Kidney Disease are excluded
given limited evidence of association with severe RSV disease.
Lung disease
Cardiovascular disease
Moderate or severe  immune compromise
Diabetes Mellitus with end -organ damageNeurologic or neuromuscular conditions
Chronic kidney disease, advanced
Hematologic disorders
Liver disorders
Severe  obesity
(body mass index ≥40 kg/m2)

8•Chronic cardiovascular disease (e.g., heart failure,
coronary artery disease, congenital heart disease;
excluding isolated hypertension )
•Chronic lung disease (e.g., chronic obstructive
pulmonary disease [COPD], emphysema, asthma,
interstitial lung disease, cystic fibrosis)
•Chronic kidney disease, advanced (e.g., stages 4 –5,
dependence on hemodialysis or other renal
replacement therapy)
•Diabetes mellitus with end -organ damage (e.g.,
diabetic nephropathy, neuropathy, retinopathy, or
cardiovascular disease)
•Severe obesity (body mass index ≥40 kg/m2)
•Decreased immune function from disease or drugs
(i.e., immunocompromising conditions *)•Neurologic or neuromuscular conditions (e.g.,
neuromuscular conditions causing impaired airway
clearance or respiratory muscle weakness; excluding
history of stroke without impaired airway clearance )
•Liver disorders (e.g., cirrhosis)
•Hematologic conditions (e.g., sickle cell disease,
thalassemia)
•Frailty
•Residence in a nursing home or other long -term
care facility
•Other chronic medical conditions or risk factors
that a health care provider determines would
increase the risk of severe disease due to
respiratory infectionChronic medical conditions and risk factors for a risk -based recommendation for RSV
vaccination in adults aged 60 –74 years
*List of immunocompromising conditions would match the existing list from the COVID -19 vaccination Interim Clinical Consideratio ns:
https://www.cdc.gov/vaccines/covid -19/clinical -considerations/interim -considerations -us.html#immunocompromised
9Other factors associated with increased risk of
severe RSV disease
Residence in a nursing home or other long -term care
facility (L TCF)*
Frailty
Other factors determined to increase risk of severe disease due to
respiratory infection
*Long -term care facilities do NOT include retirement communities or senior independent living communities in which residents are  able to perform activities of
daily living without assistance.
10
Other considerations
11▪RSV vaccination should be given
ONL Y to adults who have not yet
received a dose of RSV vaccine.
▪At this time, it is anticipated that
adults may need additional doses of
RSV vaccine in the future, but ideal
revaccination timing is not yet
known. Adults who have already
received a dose of RSV vaccine
DO NOT need to receive
another dose this year. RSV vaccination will have the
most benefit if given in late
summer or early fall .
▪This means from August to
October in most of the United
States.
▪Note this is not a formal
seasonal recommendation for
RSV vaccination. Older adults
may continue to receive RSV
vaccination year -round.
12In accordance with General Best Practice Guidelines for
Immunization, coadministration of RSV vaccines with other
adult vaccines is acceptable.*
*ACIP Timing and Spacing Guidelines for Immunization | CDC  This includes giving RSV vaccines simultaneously with
seasonal influenza vaccines, COVID -19 vaccines,
pneumococcal vaccines, Td/Tdap, and recombinant zoster
vaccine (Shingrix) .Co-administration of RSV vaccines and other vaccines
13
For more information, contact CDC
1-800 -CDC -INFO (232 -4636)
TTY:  1 -888 -232-6348    www.cdc.gov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official
position of the Centers for Disease Control and Prevention.
Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation
use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.

Summary: 1 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. ACIP Adult RSV Work Group Clinical Considerations Respiratory Syncytial Virus (RSV) in Adults 60 and older  Michael Melgar, MD Amadea Britton, MD Co-Leads, Adult RSV…


01 Vaxelis Loehr 508

Introduction to Session:
Combined Diphtheria and Tetanus Toxoids and Acellular
Pertussis, Inactivated Poliovirus, Haemophilus influenzae
Type b Conjugate, and Hepatitis B vaccine (Vaxelis)
Jamie Loehr, MD
Chair, ACIP Hib/Meningococcal Vaccines Work Group
June 26, 2024National Center for Immunization & Respiratory Diseases
1
ACIP Meningococcal/Hib Vaccines Work Group
▪ ACIP Members on the WG
•Jamie Loehr (Chair)
•Wilbur Chen
▪ Ex Officio WG Members
•Margaret Bash (FDA)
•Matthew Clark (IHS)
•Xin-Xing Gu (NIH)
▪ WG Liaisons and Consultants
•Amra Resic  (AAFP)
•Mary Healy (AAP)
•Barb Fluty (ACHA)
•Karyn Lyons (AIM)
•Paul Cieslak (CSTE)
•Kathy Hsu (IDSA)
•Pamela Doyon -Plourde (NACI)
•Jeff Goad (NFID)
•Jessica Cataldi (PIDS)
•Amy Middleman (SAHM)
•Kathy Poehling (Wake Forest)
•Lynn Bahta (Minnesota Department of Health)
•David Stephens (Emory)
▪ GRADE/ EtR Support
•Doug Campos -Outcalt (Arizona)
•Rebecca Morgan (Case Western Reserve)▪ 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)
•Gabrielle Cooper (DBD/NCIRD)
•Noele Nelson (DBD/NCIRD)
•Alison Albert (DBD/NCIRD)
•Shelby Miller (DBD/NCIRD)
•Marc Fischer (DIDRI/NCEZID)
•Xiaoyu Dong (ISD/NCIRD)
•Andrew Leidner (ISD/NCIRD)
•Ismael Ortega -Sanchez (CORVD/NCIRD)
•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)
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 DTaP-IPV-Hib-HepB (Vaxelis) be included with
PRP-OMP (PedvaxHIB) in the preferential
recommendation for American Indian and Alaska Native
(AI/AN) infants based on the Hib component?
4
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
February 2024 ACIP Meeting Presentations
▪Epidemiology of invasive Hib disease in AI/AN populations and
evidence supporting the existing preferential recommendation for
PedvaxHIB
▪Clinical trial data on post -dose 1 immunogenicity of Vaxelis vs.
PedvaxHIB
▪Preliminary Work Group considerations
5
The 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, discussion, and voteTopic Presenter
Evidence to Recommendations and
Proposed Recommendations: Use of
Vaxelis among American Indian and
Alaska Native Infants Dr. Jennifer Collins (CDC/NCIRD)
Updated Vaccines for Children (VFC)
ResolutionDr. Jeanne Santoli (CDC/NCIRD)
The use of trade names is for identification purposes only and does not imply endorsement by CDC.

Summary: Introduction to Session:  Combined Diphtheria and Tetanus Toxoids and Acellular  Pertussis, Inactivated Poliovirus, Haemophilus influenzae  Type b Conjugate, and Hepatitis B vaccine (Vaxelis)  Jamie Loehr, MD Chair, ACIP Hib/Meningococcal Vaccines Work Group June 26, 2024National Center for Immunization & Respiratory Diseases 1 ACIP Meningococcal/Hib Vaccines Work Group ▪ ACIP Members on the WG •Jamie Loehr (Chair) •Wilbur Chen ▪ Ex Officio WG Members •Margaret Bash (FDA) •Matthew Clark (IHS)…


02 Vaxelis Collins 508

Evidence to Recommendations and Proposed
Recommendations: Use of Vaxelis among
American Indian and Alaska Native Infants
Jennifer Collins, MD, MSc
Co-Lead, ACIP Hib/Meningococcal Vaccines Work Group
June 26, 2024National Center for Immunization & Respiratory Diseases

2▪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
–Estimated clinical efficacy 95% ─100%
–Invasive Hib disease is uncommon in children who are fully vaccinated Haemophilus influenzae type b (Hib)
polysaccharide conjugate vaccines remain
the primary prevention strategy for Hib disease
2
3Current 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. 3
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
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- 14
The use of trade names is for identification purposes only and does not imply endorsement by CDC.PedvaxHIB (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
4
5Vaxelis (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▪Post -dose 1 immunogenicity data not previously available
▪Lower dose of PRP -OMP than PedvaxHIB
5
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
6Policy question
Should DTaP-IPV-Hib-HepB (Vaxelis) be included with
PRP-OMP (PedvaxHIB) in the preferential
recommendation for American Indian and Alaska Native
(AI/AN) infants based on the Hib component?
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
Public health problem
Is invasive Hib disease among American Indian and Alaska Native infants a
problem of public health importance?
8•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
•Most common clinical syndromes of invasive Hib disease in the post -
vaccine eraPublic health problem
Bacteremic
pneumonia
MeningitisBacteremia
without a focus

9▪Incidence of invasive Hib disease
declined >99% with introduction of
Hib vaccines
▪American Indian/Alaska Native
children aged <5 years have a 31 -
fold higher incidence of invasive Hib
disease than non -Native childrenIncidence per 100,000 of invasive Hib disease
among children aged <5 years, 2011 –2020
0123
AI/AN Non-AI/AN2.5
0.08051015202530
1980 1990 2000 2010Incidence per 100,000 of invasive Hib disease
among children aged <5 years, 1980 –2012Public health problem
10▪Is invasive Hib disease a public health problem among American Indian
and Alaska Native populations?Public health problem:
Work Group determination
No Probably no Probably yes Yes Varies Don’t know
Most common  2nd most common
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?
12PICO components
Population American Indian and Alaska Native infants
Intervention Vaxelis (DTaP -IPV-Hib-HepB )
Comparison PedvaxHIB  (PRP -OMP)
Outcomes- Invasive Hib disease
- Post -dose 1 immunity
- Post -primary series immunity
- Serious adverse events
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
13GRADE evidence retrieval
Records identified and
screened
(n=2,332)
Records excluded based on title (n=2,290):
Not a Hib vaccine clinical trial (n=2,070)
Different Hib vaccine (n=191)
Did not enroll AI/AN infants (n=29)Abstracts assessed for
eligibility
(n=42) Records excluded based on abstract/full text (n=41):
Not a Hib vaccine clinical trial (n=6)
Different Hib vaccine (n=10)
Did not enroll AI/AN infants (n=16)
Other PICO components not aligned (n=9) Articles included in GRADE
(n=1)
*Search was limited to studies in English from 2014 –present based on earliest clinical trials of Vaxelis having been published in 2015. Two reviewers screened titles, abstracts and full-text records,
as indicated, to determine whether records should be included.
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
14GRADE Table 2: Outcomes and Rankings
Outcome ImportanceIncluded in
evidence profile
Invasive Hib disease Important No
Post -dose 1 immunity Critical Yes
Post -primary series immunity Important Yes
Serious adverse events Critical Yes
15▪Immunity and serious adverse events assessed using data from one phase
IV, prospective, open -label randomized controlled clinical trial
–Enrolled healthy infants
•Born at gestational age ≥35 weeks
•Aged 42 –90 days at the time of first vaccination
•Identified as AI/AN by parent/legally authorized representative
–Randomized to Vaxelis vs. PedvaxHIB
•Vaxelis administered at ages 2, 4, and 6 months
•PedvaxHIB  administered at ages 2 and 4 months
–Compared antibody levels before vaccination vs. day 30, 120, and 150 post -
dose 1
–Safety monitoring for serious adverse events on day 0, 30, 60, 120, and 150  Available evidence
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
16Post-dose 1 immunity
▪Anti-Hib IgG geometric mean
concentration (GMC) ratio (Vaxelis:
PedvaxHIB ) 30 days post -dose 1
met pre -specified non -inferiority
criterion
▪The proportion of infants with anti -
Hib concentration above the
putative correlate of short -term
protection 30 days post -dose 1 was
similar between groups
–Vaxelis 75.7%
–PedvaxHIB  71.2%Slide credits: Laura Hammitt’s  February 2024 ACIP Presentation
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
17GRADE evidence profile: post-dose 1 immunity
Assessed via proportion with anti- Hib IgG concentration ≥0.15 µg/mL 30 days post -dose 1
Certainty assessment Summary of findings Importance
#
studiesStudy
designRisk of
biasInconsistency Indirectness Imprecision Other
considerations# patients Effect Certainty
Vaxelis
n/N
%
(95% CI)PedvaxHIB
n/N
%
(95% CI)Relative
risk
(95%
CI)Absolute risk
(95% CI)
1 RCTNot
seriousaNot
seriousNot seriousb,c,dSeriouse None 115/152
(75.7%)104/146
(71.2%)1.06
(0.93 –
1.22)4,274 more
per 100,000
(from 4,986
fewer to
15,671 more)Moderate Critical
a Similar loss to follow -up for anti -Hib IgG concentration 30 days post -dose 1: Vaxelis: 15/167 (9%), PedvaxHIB : 20/166 (12%), p=0.36. Open -label study design would not affect
immune response. Median time of post -dose 1 blood draw was similar between groups: Vaxelis 34 days (IQR 32 –37 days) versus PedvaxHIB  34 days (IQR 31 –39 days).
b Immunity is inferred from proportion with anti -Hib concentration above the putative correlate of short -term protection.
C As modeled by constrained longitudinal data analysis, anti -Hib GMC 30 days post -dose 1 for Vaxelis group (0.41; 95% CI: 0.33 –0.51) was non -inferior to that of the PedvaxHIB
group (0.40; 95% CI: 0.31 –0.50). Ratio of GMCs ( Vaxelis:PedvaxHIB ): 1.03 (95% CI: 0.75 –1.41); the pre -specified non -inferiority criterion was met based on the lower bound of
the 95% CI being >0.67.
d Study was conducted among Navajo Nation and Alaska Native infants and may not be generalizable to other American Indian popul ations; WG members determined this did
not warrant a downgrade.
e Downgraded because the absolute effect confidence interval is wide.
 The use of trade names is for identification purposes only and does not imply endorsement by CDC.
18▪The proportion of infants with
anti-Hib concentration above the
putative correlate of long -term
protection 150 days post -dose 1
was higher in the Vaxelis group
(83.6%) than in the PedvaxHIB
group (71.7%, p<0.05)
▪Antibody titers were not
collected beyond day 150 post -
dose 1Post-primary series immunity
Slide credit: Laura Hammitt’s  February 2024 ACIP Presentation
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
19GRADE evidence profile: post-primary series immunity
Assessed via proportion with anti- Hib IgG concentration ≥1.0 µg/mL 150 days post -dose 1
Certainty assessment Summary of findings Importance
#
studiesStudy
designRisk of
biasInconsistency Indirectness Imprecision Other
considerations# patients Effect Certainty
Vaxelis
n/N
%
(95% CI)PedvaxHIB
n/N
%
(95% CI)Relative
risk
(95%
CI)Absolute
risk
(95% CI)
1 RCTNot
seriousaNot
seriousNot seriousb,cSeriousd None 107/128
(83.6%)84/117
(71.8%) 1.16
(1.02 –
1.34) 11,487 more
per 100,000
(from 1,436
more to
24,410
more)Moderate Important
a Similar loss to follow -up for anti -Hib IgG concentration 150 days post -dose 1: Vaxelis 39/167 (23%), PedvaxHIB  49/166 (30%), p=0.20. Open -label study design would not
affect immune response. Median time of day 150 blood draw was similar between groups: Vaxelis 174 days (IQR 163 –187 days) versus PedvaxHIB  180 days (IQR 162 –189
days).
b Immunity is inferred from proportion with anti -Hib concentration above the putative correlate of long -term protection.
c Study was conducted among Navajo Nation and Alaska Native infants and may not be generalizable to other American Indian popul ations; WG members determined this did
not warrant a downgrade.
d Downgraded because the absolute effect confidence interval is wide.

The use of trade names is for identification purposes only and does not imply endorsement by CDC.
20General safety of Vaxelis (DTaP-IPV-Hib-HepB)
▪In pre -licensure clinical trials, the safety profile was consistent with that of
licensed comparator vaccines except higher rate of fever than with DTaP -IPV/Hib
(Pentacel ) (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 Vaccine Adverse Event Reporting System ( 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.
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
21▪The frequency of SAEs was similar
between groups
–Vaxelis (5%)
–PedvaxHIB  (7%)
▪The most common SAE was acute
respiratory infection
▪No SAEs were deemed related to
study participation GRADE: Serious adverse events among
AI/AN infants in the Hibvax Study
Slide credit: Laura Hammitt’s  February 2024 ACIP Presentation
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
22GRADE evidence profile: serious adverse events
Assessed via proportion with SAEsa
Certainty assessment Summary of findings Importance
#
studiesStudy
designRisk of
biasInconsistency Indirectness Imprecision Other
considerations# patients Effect Certainty
Vaxelis
n/N
%
(95% CI)PedvaxHIB
n/N
%
(95% CI)Relative
risk
(95%
CI)Absolute
risk
(95% CI)
1 RCTNot
seriousbNot
seriousNot seriouscSeriousd None9/167
(5.4%) e12/166
(7.2%)e0.75
(0.32 –
1.72)1,807
fewer per
100,000
(from
4,916
fewer to
5,205
more)Moderate Critical
a From the time of the first dose of study vaccine to the end of the last study visit (approximately 5 months).
b Similar loss to follow -up through the last study visit: Vaxelis 21/166 (13%) PedvaxHIB  16/167 (10%)  p=0.37. Open -label study design may bias reporting of SAEs but WG members
determined this did not warrant a downgrade.
c Study was conducted among Navajo Nation and Alaska Native infants and may not be generalizable to other American Indian popul ations; WG members determined this did not
warrant a downgrade.
d Downgraded because the absolute effect confidence interval is wide.
e In the Vaxelis group 10 SAEs occurred among 9 participants. In the PedvaxHIB group, 15 SAEs occurred among 12 participants. The most common SAE was acute respiratory infection
21/25 (84%). No SAEs were deemed related to study participation.
 The use of trade names is for identification purposes only and does not imply endorsement by CDC.
23GRADE Summary Table
Type Outcome ImportanceDesign
(# studies)FindingsEvidence
type*
BenefitsInvasive Hib disease n/a No data available ND
Post -dose 1
immunityCritical RCT (1)The proportion participants with anti -Hib
concentration ≥0.15 µg/mL* 30 days post -dose 1
was similar between groupsModerate
Post -primary series
immunityImportant RCT (1)The proportion participants with anti -Hib
concentration ≥1.0 µg/mL** 150 days post -dose 1
was higher in the Vaxelis group. Antibody titers
were not available beyond day 150 post -dose 1.Moderate
HarmsSerious adverse
eventsCritical RCT (1)The proportion of SAEs was similar between
groups; no SAEs were deemed related to study
participationModerate
*Putative correlate of short -term protection
**Putative correlate of long -term protection
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
24▪How substantial are the desirable anticipated effects overall and for each
main outcome for which there is a desirable effect?
▪How substantial are the undesirable effects overall and for each main
outcome for which there is an undesirable effect?Benefits and harms:
Work Group determination
Minimal Small Moderate Large Varies Don’t know
Most common    2nd most common           3rd most common                  MajorityMinimal Small Moderate Large Varies Don’t know
25▪Do the desirable effects outweigh the undesirable effects?
▪What is the overall certainty of evidence for the critical outcomes?Benefits and harms:
Work Group determination
Most common  2nd most common        Majority Favors
intervention
(Vaxelis only)Favors
comparison
(PedvaxHIB  only)Favors
both
(Vaxelis & PedvaxHIB )Favors
neitherUnclear
High Moderate Low Very low
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
Values
- Does the target population feel that the desirable effects are large relative to
the undesirable effects?
- Is there important uncertainty about or variability in how much people value
the main outcome?
27▪Limited data were available
▪Vaxelis would provide an additional option for AI/AN infants
▪In collaboration with CDC’ Office of Tribal Affairs and Strategic Alliances
(OTASA), NCIRD held a listening session with tribal communities in January
2024
–80 attendees, including
•9 from tribes or tribal serving organizations
•46 from Indian Health Service (IHS)
–Key questions and concerns raised by participants for WG consideration
•Will Vaxelis offer the same protection as PedvaxHIB ?
•Need to monitor for possible breakthrough cases
•Safety and side effects  Values
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
28▪Does the target population feel the desirable effects are large relative to
the undesirable effects?
▪Is there important uncertainty about, or variability in, how patients value
the outcomes?Values:
Work Group determination
No Probably no Probably yes Yes Varies Don’t know
No Probably no Probably yes Yes Varies Don’t know
Most common   2nd most common          3rd most common   4th most common                     Majority
Acceptability
Is the intervention acceptable to key stakeholders?
30▪Limited data were available
▪Vaxelis would reduce the number of injections to complete the childhood
immunization series for those who receive it and may therefore improve
acceptability for parents/guardians and medical providers
▪CDC’s General Best Practice Guidance for Immunization and American
Academy of Pediatrics Red Book  both state a general preference for
combination vaccines over separate injections of equivalent component
vaccines1,2
–Considerations should include provider assessment, patient preference,
and the potential for adverse events.1
▪Proposed policy option to add Vaxelis retains flexibility for providers to
continue using PedvaxHIBAcceptability
1General Best Practice Guidelines for Immunization. Best Practice Guidance of the ACIP. https://www.cdc.gov/vaccines/hcp/acip -recs/general -recs/index.html
2American Academy of Pediatrics. Red Book 2018 Report of the Committee on Infectious Diseases. 31st Edition.
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
31General best practice guidance for
immunization: combination vaccines
Potential advantages Potential disadvantages
•Improved vaccine coverage rates
•Timely catch -up immunizations
•Reduced shipping and stocking costs
•Reduced costs for extra health care visits necessitated by
deferral of vaccination
•Facilitation of additional new vaccines into vaccination
programs•Adverse events that might occur more frequently with
combination vaccines than with individual components
•Confusion and uncertainty about selection of vaccine
combinations and schedules for subsequent doses
•Extra doses of certain antigens in the combination product
1General Best Practice Guidelines for Immunization. Best Practice Guidance of the ACIP. https://www.cdc.gov/vaccines/hcp/acip -recs/general -recs/index.html
32▪Is the intervention acceptable to key stakeholders?
–Are there key stakeholders that would not accept the distribution of
benefits, harms, and costs?
–Are there key stakeholders that would not accept the costs or
undesirable effects in the short term for the desirable effects in the
future?Acceptability:
Work Group determination
No Probably no Probably yes Yes Varies Don’t know
Most common   2nd most common          3rd most common                  Majority
Resource use
- Is the intervention a reasonable and efficient allocation of resources?
34Vaxelis 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.Option 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.
35Pediatric/Vaccines for Children (VFC) Vaccine Price List
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.
IPV is inactivated polio vaccine.Vaccine Trade name CDC cost/dose Private sector
cost/dose
DTaP -IPV-Hib-HepB Vaxelis $100.59 $150.85
PRP-OMP PedvaxHIB $16.14 $29.71
DTaP -HepB -IPV Pediarix $66.07 $97.97
DTaPDaptacel $21.69 $29.31
Infanrix $21.66 $28.80
IPV IPOL $16.46 $42.64
HepBEngerix  B $17.38 $28.42
Recombivax  HB $14.59 $27.12
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
36Estimated cost of vaccine options that protect against
the 6 pathogens in Vaxelis
*Vaccine cost ranges reflect different costs for DTaP ( Daptacel  vs. Infanrix) and HepB  (Engerix  B vs. Recombivax  HB).
**Assumptions: private sector administration cost $34.53 for first vaccine based on estimates from a 2014 study, adjusted for  inflation.1 A factor of 0.6 was used to calculate the p rivate  sector
administration cost of $20.72 for subsequent doses at the same visit based a 2019 study.2 Public sector administration costs were assumed to be half of private sector costs.3
1Tsai Y et al. Prev Med Rep. 2019 Jun 7:15:100917. doi: 10.1016/j.pmedr.2019.100917
2Tsai Y et al. .Am J Prev Med. 2019 Aug;57(2):180 -190. doi: 10.1016/j.amepre.2019.03.011
3Tsai Y. Med Care. 2018 Jan; 56(1): 54 –61.OptionVaccines
(# doses to complete
childhood series)Total CDC cost
(vaccines only*)Total CDC cost
(vaccines + admin**)Total private sector cost
(vaccines only*)Total private sector cost
(vaccines + admin**)
1Vaxelis (3)
$339.57 –339.60 $419.01 –419.04 $511.06 –511.57 $669.90 –670.41 PedvaxHIB  (1)
DTaP (1)
2Pediarix  (3)
$268.29 –268.32 $368.45 –368.48 $411.84 –412.35 $612.12 –612.63 PedvaxHIB  (3)
DTaP (1)
3PedvaxHIB  (3)
$213.62 –219.32 $365.58 –371.28 $386.49 –391.13 $690.37 –695.01DTaP (4)
IPV (3)
HepB  (2)
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
37OptionVaccines
(# doses to complete
childhood series)Total CDC cost
(vaccines only*)Total CDC cost
(vaccines + admin**)Total private sector cost
(vaccines only*)Total private sector cost
(vaccines + admin**)
1Vaxelis (3)
$339.57 –339.60 $419.01 –419.04 $511.06 –511.57 $669.90 –670.41 PedvaxHIB  (1)
DTaP (1)
2Pediarix  (3)
$268.29 –268.32 $368.45 –368.48 $411.84 –412.35 $612.12 –612.63 PedvaxHIB  (3)
DTaP (1)
3PedvaxHIB  (3)
$213.62 –219.32 $365.58 –371.28 $386.49 –391.13 $690.37 –695.01DTaP (4)
IPV (3)
HepB  (2)Vaccine only costs are higher for option 1
(i.e., using Vaxelis)
*Vaccine cost ranges reflect different costs for DTaP ( Daptacel  vs. Infanrix) and HepB  (Engerix  B vs. Recombivax  HB).
**Assumptions: private sector administration cost $34.53 for first vaccine based on estimates from a 2014 study, adjusted for  inflation.1 A factor of 0.6 was used to calculate the p rivate  sector
administration cost of $20.72 for subsequent doses at the same visit based a 2019 study.2 Public sector administration costs were assumed to be half of private sector costs.3
1Tsai Y et al. Prev Med Rep. 2019 Jun 7:15:100917. doi: 10.1016/j.pmedr.2019.100917
2Tsai Y et al. .Am J Prev Med. 2019 Aug;57(2):180 -190. doi: 10.1016/j.amepre.2019.03.011
3Tsai Y. Med Care. 2018 Jan; 56(1): 54 –61.
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
38OptionVaccines
(# doses to complete
childhood series)Total CDC cost
(vaccines only*)Total CDC cost
(vaccines + admin**)Total private sector cost
(vaccines only*)Total private sector cost
(vaccines + admin**)
1Vaxelis (3)
$339.57 –339.60 $419.01 –419.04 $511.06 –511.57 $669.90 –670.41 PedvaxHIB  (1)
DTaP (1)
2Pediarix  (3)
$268.29 –268.32 $368.45 –368.48 $411.84 –412.35 $612.12 –612.63 PedvaxHIB  (3)
DTaP (1)
3PedvaxHIB  (3)
$213.62 –219.32 $365.58 –371.28 $386.49 –391.13 $690.37 –695.01DTaP (4)
IPV (3)
HepB  (2)Total costs are similar accounting for administration
costs
*Vaccine cost ranges reflect different costs for DTaP ( Daptacel  vs. Infanrix) and HepB  (Engerix  B vs. Recombivax  HB).
**Assumptions: private sector administration cost $34.53 for first vaccine based on estimates from a 2014 study, adjusted for  inflation.1 A factor of 0.6 was used to calculate the p rivate  sector
administration cost of $20.72 for subsequent doses at the same visit based a 2019 study.2 Public sector administration costs were assumed to be half of private sector costs.3
1Tsai Y et al. Prev Med Rep. 2019 Jun 7:15:100917. doi: 10.1016/j.pmedr.2019.100917
2Tsai Y et al. .Am J Prev Med. 2019 Aug;57(2):180 -190. doi: 10.1016/j.amepre.2019.03.011
3Tsai Y. Med Care. 2018 Jan; 56(1): 54 –61.
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
39▪Cost is similar for Vaxelis and other vaccine options that cover the same
pathogens, accounting for administration costs
▪Resource use has been acceptable for the general U.S. population;
equitable to use the same standard for AI/AN childrenResource use (summary)
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
40▪Is using Vaxelis among American Indian and Alaska Native infants a
reasonable and efficient allocation of resources?Resource use:
Work Group determination
No Probably no Probably yes Yes Varies Don’t know
The use of trade names is for identification purposes only and does not imply endorsement by CDC.Most common   2nd most common          3rd most common                 Majority
Equity
- What would be the impact on health equity?
42▪Limited data were available
▪The option to use a combination vaccine may improve equity by
–Improving reliability of the vaccine supply
–Improving Hib vaccination uptake among AI/AN populations, who
are disproportionately at risk for invasive Hib diseaseEquity
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
43▪What would be the impact of using Vaxelis among American Indian and
Alaska Native infants on health equity? Equity:
Work Group determination
Minimal* Small Moderate Large** Varies Don’t know
*Would not reduce disparities
**Would greatly reduce disparities
Most common   2nd most common          3rd most common   4th most common                     Majority
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
Feasibility
- Is the intervention feasible to implement?
45▪Widely used in the general U.S. population with >7.4 million doses distributed in the United
States (as of Q1 2024)1
▪Adding Vaxelis to the preferential recommendation for AI/AN infants would
–Increase flexibility for patients and providers
–Reduce the number of injections to complete the childhood immunization series for those who
receive it
▪Neither Vaxelis nor PedvaxHIB  require reconstitution
▪Shelf life of Vaxelis (4 years) is longer than that of PedvaxHIB  (3 years)
▪Vaxelis cannot be used for the booster dose; clinics will need to stock additional products
–Stocking PRP -OMP ( PedvaxHIB ) for the Hib booster dose would maintain parent/guardian and
provider flexibility to choose this for doses 1 –3
–Stocking PRP -T is also an option
•Vaxelis primary series with a heterologous booster (PRP -T) was shown to produce a robust
immune response in a small study2
•Risk of inadvertent administration of PRP -T for doses 1 –3 with a less robust immune
response following doses 1 and 2Feasibility
1Per the manufacturer
2Wilck et al. Vaccine . 2021;39(9):1428- 1434.
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
46▪Is using Vaxelis among American Indian and Alaska Native infants feasible
to implement?Feasibility:
Work Group determination
No Probably no Probably yes Yes Varies Don’t know
The use of trade names is for identification purposes only and does not imply endorsement by CDC.Most common  2nd most common        Majority
Summary

EtR Domain Question Work group
determination
Public health problem Is invasive Hib disease among American Indian and Alaska Native children a problem of
public health importance?Yes
Benefits and harms How substantial are the desirable anticipated effects? Moderate
How substantial are the undesirable anticipated effects? Minimal
Do the desirable anticipated effects outweigh the undesirable effects? Favors both
(Vaxelis & PedvaxHIB )
What is the overall certainty of the evidence for the critical outcomes? Moderate
Values Does the target population feel the desirable effects are large relative to the undesirable
effects?Probably yes or yes
Is there important variability in how patients value the outcome? Probably no, probably
yes or don’t know
Acceptability Is the intervention acceptable to key stakeholders? Probably yes
Resource use Is the intervention a reasonable and efficient allocation of resources? Yes
Equity What would be the impact of the intervention on health equity? Moderate
Feasibility Is the intervention feasible to implement? Yes
48The use of trade names is for identification purposes only and does not imply endorsement by CDC.Favorable             Uncertain
49Balance of Consequences
Undesirable
consequences
clearly outweigh
desirable
consequences in
most settings Undesirable
consequences
probably
outweigh
desirable
consequences in
most settingsThe balance
between
desirable and
undesirable
consequences is
closely balanced
or uncertain Desirable
consequences
probably
outweigh
undesirable
consequences in
most settingsDesirable
consequences
clearly outweigh
undesirable
consequences in
most settingsThere is
insufficient
evidence to
determine the
balance of
consequences
Most common   2nd most common  Majority of WG members think desirable consequences probably
outweigh undesirable consequences in most settings
Is there sufficient information to move forward with a recommendation?
Yes No
49
50Most common  2nd most common Work Group Interpretation:
Should DTaP-IPV-Hib-HepB (Vaxelis) be included with PRP-OMP
(PedvaxHIB) in the preferential recommendation for American
Indian and Alaska Native infants based on the Hib component?
We do not recommend the intervention
We recommend the intervention
Majority of WG members favored recommending the intervention

50The use of trade names is for identification purposes only and does not imply endorsement by CDC.
51ACIP recommends DTaP-IPV-Hib-HepB (Vaxelis®) should be included with
PRP-OMP (PedvaxHIB®) in the preferential recommendation for American
Indian and Alaska Native infants based on the Haemophilus influenzae
type b (Hib) Hib component.Draft proposal language
51The use of trade names is for identification purposes only and does not imply endorsement by CDC.
Acknowledgments
▪ ACIP Members on the WG
– Jamie Loehr (Chair)
– Wilbur Chen
▪ Ex Officio WG Members
– Margaret Bash (FDA)
– Matthew Clark (IHS)
– Xin-Xing Gu (NIH)
▪ WG Liaisons and Consultants
– Amra Resic  (AAFP)
– Mary Healy (AAP)
– Barb Fluty (ACHA)
– Karyn Lyons (AIM)
– Paul Cieslak (CSTE)
– Kathy Hsu (IDSA)
– Pamela Doyon -Plourde (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)
– Veronica Pinell -McNamara (DBD/NCIRD)
– Amy Rubis (DBD/NCIRD)
– Gabrielle Cooper (DBD/NCIRD)
– Noele Nelson (DBD/NCIRD)
– Alison Albert (DBD/NCIRD)
– Angela Jiles (DBD/NCIRD)
– Shelby Miller (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) 52
Thank you!
For more information, contact CDC
1-800-CDC-INFO (232-4636)
TTY:  1- 888- 232-6348    cdc.gov
Follow us on X (Twitter) @CDCgov & @CDCEnvironment
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position o f
the U. S. Centers for Disease Control and Prevention.
53

Summary: Evidence to Recommendations and Proposed  Recommendations: Use of Vaxelis among  American Indian and Alaska Native Infants Jennifer Collins, MD, MSc Co-Lead, ACIP Hib/Meningococcal Vaccines Work Group June 26, 2024National Center for Immunization & Respiratory Diseases  2▪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…


03 POLIO Kidd 508

Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
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.Clinical Considerations for Children who Received
Fractional Dose Inactivated Polio Vaccine ( fIPV ) in
Other Countries
Sarah Kidd, MD, MPH
ACIP Meeting
February 28, 2024

▪Wild poliovirus type 2 eradicated in 2015
▪Global switch and withdrawal of Sabin type 2 virus from OPV in April 2016:
–Replaced all trivalent OPV ( tOPV ; types 1, 2, and 3) with bivalent OPV ( bOPV ; types 1 and 3)
–≥1 dose IPV recommended as part of routine immunization in all countries using bOPV
▪Based on clinical trial data and limited IPV availability, WHO supports use of 2
fractional doses of IPV (1/5 full dose IPV) given intradermally in place of single full
IPV dose (intramuscular)Background
WHO. World Epidemiological Record 2016;91:561 –82.
WHO. World Epidemiological Record 2021;96:613 –32.
https://www.who.int/teams/immunization -vaccines -and-biologicals/diseases/poliomyelitis -(polio)
ONE fractional IPV ( fIPV ) dose is LESS immunogenic than
one full IPV dose
Meta -analysis of percent that seroconverted for poliovirus type 2 ( Mashunye  2021)
Mashunye et al. Lancet Infect Dis 2021;21:1161 –74.

TWO fractional IPV ( fIPV ) doses are MORE immunogenic
than one full IPV dose
Slide adapted from Concepcion Estivariz.
Data from Snider et al. Lancet 2019; 393:2624. 0102030405060708090
Type 1 Type 2 Type 3Percent with seroconversion at 18 weeks
2 fIPV 6 & 14 wk 1 IPV 6 wk 1 IPV 14 wk
* P< 0.01 versus 2 fIPV doses  **
**
* *
▪6 countries (~20% of global birth cohort) use 2 fIPV doses + ≥3 bOPV  doses in routine
childhood immunization schedule
–Bangladesh, Cuba, Ecuador, India, Nepal, Sri Lanka
Example polio vaccination schedule (India):Current Use of fIPV  in Routine Immunization Globally
Birth 6 weeks 10 weeks 14 weeks 16–24
monthsTotal doses
bOPV X X X X X 5 bOPV
fIPV X X 2 fIPV
▪Recommended polio vaccination
–4 total IPV doses, administered at 2, 4, 6 –18 months, and 4 –6 years OR
–3 total IPV doses if 3rd dose administered after 4th birthday and ≥6 months after 2nd dose
▪For vaccines administered outside of US
–Only tOPV  or IPV doses considered valid for US vaccination schedule
Example polio vaccination schedule (India):Current US Guidance
Birth 6 weeks 10 weeks 14 weeks 16–24
monthsTotal
doses
bOPV X X X X X 5 bOPV
fIPV X X 2 fIPVCurrent US guidance:
•None of these
doses considered
valid in US
•Needs 3 –4 full IPV
doses in US
Should 2 fractional IPV doses administered outside of the United States
be counted as either 1 or 2 doses towards the US vaccination schedule?Question for Work Group:
▪Previous meta -analysis published in 2021 ( Mashunye  et al)
▪Literature review using same search terms; searched Medline, Embase, Cochrane
Library, Scopus, and ClinicalTrials.gov
–Randomized clinical trials
–Compared 2 fIPV doses to either 1 or 2 IPV doses
–Published between January 1, 2019 and June 30, 2023
▪Outcomes
–Seroconversion for poliovirus type 2
•Change from seronegative (titer <1:8) to seropositive (titer ≥1:8) OR
•≥4-fold increase in antibody titer over expected decline in maternal antibodies
–Changes in geometric mean titersMethods: Updated Meta -Analysis
Mashunye et al. Lancet Infect Dis 2021;21:1161 –74.
Seroconversion: 2 fIPV  Doses vs. 1 IPV Dose

Seroconversion: 2 fIPV  Doses vs. 2 IPV Doses

Seroconversion: 2 fIPV  doses are less favorable vs. 2 IPV
doses when given at younger age
6 and 14 weeks
2 and 4 months
10 and 14 weeks
4 and 8 months
14 weeks and 36 weeks
3 and 11 –15 months14 weeks and 9 months4 and 8 months6 and 10 weeksAge
Median Antibody Titers Lower After 2 fIPV  vs. 2 IPV Doses
Resik  2010 (3 doses at 6, 10, and 14 weeks)
 Mohammed 2010 (3 doses at 2, 4, and 6 months)
Resik  2020 (2 doses at 4 and 8 months)
fIPVIPVfIPVIPV
Age fIPV IPV
Resik  2013 4 and 8 months 898 (713 -≥1448) ≥1448 (≥1448 -≥1448)
Aziz 2022 9-13 and 11 -15 months 455 (362 -724) ≥1448 (1152 -≥1448)Resik  2013 and Aziz 2022: Median titer (95% CI) after 2 doses
Resik  et al, J Infect Dis 2010; Resik  et al, J Infect Dis 2020; Mohammed et al, N Engl J Med 2010; Resik  et al, N Engl J Med 201; Aziz et al, J Infect Dis 2022.
Geometric Mean Titers: 2 fIPV  vs. 2 IPV Doses
Bandyopadhyay et al. Lancet Infect Dis 2021;21:559 –68.
(10-14-36 weeks)
(14-36 weeks)
(10-14-36 weeks)
(14-36 weeks)4 weeks after 2 doses
IPV vs. 2 doses fIPV
(given at 10 and 14
weeks)4 weeks after 2 doses
IPV vs. 2 doses fIPV
(given at 14 and 36
weeks)
Persistence of Poliovirus Type 2 Antibodies Following 2 fIPV
or 2 IPV Doses
Saleem et al. JID 2021; 223(7)1214
Slide adapted from Concepcion Estivariz.
•As immunization
series with fIPV
reach lower final
titers, seronegativity
expected to be
reached earlier 2 IPV doses
2 fIPV  doses
▪WHO supports the use of 2 fIPV doses in place of 1 IPV dose as an IPV conservation
strategy
▪2 fIPV doses associated with higher  rates of seroconversion vs. 1 IPV dose
▪2 fIPV doses associated with slightly lower  rates of seroconversion vs. 2 IPV doses
–Especially when administered at 6 and 14 weeks; rates of seroconversion approach equivalency at older ages
of administration
▪Peak antibody titers are  lower after 2 fIPV doses vs. 2 IPV dosesSummary
▪For persons who received fractional (1/5 full dose) IPV administered intradermally
outside of the United States, 2 fractional doses of IPV ( fIPV) should be considered
valid and counted as 1 full intramuscular dose of IPV towards the US vaccination
schedule.
▪If a person received only 1 dose of fIPV, this dose should not be considered valid or
counted towards the US vaccination schedule.Proposed CDC Clinical Considerations
Questions and Discussion
▪ACIP voting members
–Oliver Brooks (Chair)
–Lynn Bahta
–Sybil Cineas
▪Liaisons
–Lynn Fisher, American Academy of Family Physicians
–Chandy C. John, American Academy of Pediatrics
–Sandra Fryhofer , American Medical Association
–Kathy Kudish, Association of Immunization Managers
–Marcus Plescia , Association of State and Territorial Health Officials
–Paul R. Cieslak , Council of State and Territorial Epidemiologists
–Christine Hahn, Council of State and Territorial Epidemiologists
–Tina Q. Tan, Infectious Diseases Society of America
–Adenike  Shoyinka , Infectious Diseases Society of America
–Mary Wilson, International Society of Travel Medicine
–Jaqueline Lawler, National Association of County and City Health Officials
–Kathy Edwards, Pediatric Infectious Diseases Society
–Joseline Zafack , Public Health Agency of Canada*Polio Work Group Members
*In the event of a Work Group poll, CDC, FDA, and Public Health Agency of Canada members are not included.▪Consultants
–Edwin Asturias
–Doug E Campos -Outcalt *
–Emily Lutterloh
–Jennifer Rosen
–Eli Rosenberg
▪FDA*
–Robin Levis
▪CDC*
–Cara Burns
–Thomas Clark
–Miranda Delahoy
–Brian Edlin
–Concepcion Estivariz
–Halle Getachew
–Sarah Kidd
–Janelle King
–Adriana Lopez
–M. Steve Oberste

Summary: Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases 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…


01 RSV Adults Kotton 508

Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation
use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.
Adult Respiratory Syncytial Virus (RSV) Session
Camille Kotton, MD
Chair, Adult RSV Work Group
Advisory Committee on Immunization Practices (ACIP)
February 29, 2024
As a reminder, ACIP recommended that adults aged ≥60 years may
receive RSV vaccination, using  shared clinical decision -making.
There are currently two licensed and recommended products for adults aged ≥60 years:
–GSK RSV vaccine (Arexvy ): a 1 -dose adjuvanted (AS01E) recombinant
prefusion F protein (preF ) vaccine.
–Pfizer RSV vaccine (Abysvo ): a 1 -dose recombinant preF  vaccine. In June 2023, ACIP made the first -ever recommendation for
the use of RSV vaccine in older adults.
https://www.cdc.gov/mmwr/volumes/72/wr/mm7229a4.htm  2
The ACIP Adult RSV Work Group shared their early interpretations of
these data and the potential role of RSV vaccination in adults younger
than 60 years, including subpopulations that would benefit most from
vaccination and equity implications.
At that time ACIP members expressed the importance of reviewing safety surveillance data to inform future preferred policy
recommendations . In October 2023, GSK presented data to ACIP demonstrating that the humoral immune response to a single dose of GSK RSV vaccine in adults
50–59 years is non -inferior to that in adults ages 60 years and older.
3
The Work Group is committed to incorporating what we are learning from
post -licensure data in a transparent way that ensures safety for the public
and clarity for providers.
The preliminary data shared today are the first in what will be a series of rigorous analyses across multiple different platforms.
CDC and the Work Group will be engaged in ongoing re- assessment and
future policy will be responsive to what is learned over the coming
months. At today’s meeting CDC and FDA will be sharing preliminary
data from multiple safety surveillance platforms.
4
Risk of severe RSV disease in adults ages 50 -59 years, especially those
with chronic medical conditions
RSV vaccine uptake among different demographic groups
Potential policy options that would transition away from shared clinical
decision -making The Work Group has simultaneously been reviewing additional
data to prepare for upcoming potential policy decisions.
5
We will open today’s session with a presentation from Moderna, who will be sharing
safety and efficacy data with ACIP for the first time from their primary Phase 2 -3 trial
evaluating mRNA -1345.The Work Group has also begun reviewing data from Moderna on their
investigational RSV vaccine (mRNA- 1345) in adults aged ≥60 years.
6
Agenda: February 29, 2024
Manufacturer presentation: Overview of Moderna’s Investigational
RSV Vaccine (mRNA -1345) in Adults ≥60 Years of Age
Risk -stratified rates of RSV -associated hospitalization among
adults
Implementation update: older adult RSV vaccination
Post -marketing safety surveillance of older adult RSV vaccination
Preliminary Analysis of Guillain -Barré Syndrome (GBS) following
RSV Vaccination among adults 65 years and older
Older adult RSV vaccination: benefits and risks discussion
Work Group interpretations and discussionDr. Rituparna Das (Moderna)
Dr. Rebecca Woodruff (CDC)
Dr. Carla Black (CDC)
Dr. Tom Shimabukuro (CDC)Dr. Patricia Lloyd (FDA)
Dr. Michael Melgar (CDC)
Dr. Amadea Britton (CDC)
7
Adult RSV Work Group Membership
8ACIP Voting Members
Camille Kotton (Chair)
Keipp Talbot
Sarah Long
Ex Officio Members
Rachel Zhang (FDA)
Nicholas Geagan (FDA)
Nadine Peart Akindele (FDA)
Sonnie Kim (NIH/NIAID)
Jeffrey Kelman (CMS)Michelle Juaneza (HRSA/VICP )
Uzo Chukwuma (IHS)
Valerie Marshall (OIDP)Consultants
Robert Atmar (Baylor Coll. of Medicine)
Helen Chu (U Washington)
Peter Donofrio (Vanderbilt University)
Marie Griffin (Vanderbilt University)
Cynthia Lucero -Obusan  (VHA)Tracy Ruckwardt (NIH/NIAID)
Jonathan Temte  (U Wisconsin)
Rebecca Morgan (Case Western)
Doug C ampos -Outcalt  (U Arizona)
Liaisons
Kenneth Schmader (AGS)
Vidya Sundareshan (ACP)Gretchen LaSalle (AAFP)April Killikelly (NACI /PHAC)
Winnie Su (NACI/ PHAC)Katherine Williams (APTR)Ruth Lynfield (NFID)Bindy Crouch (AIM)Steven Pergam (IDSA)Elizabeth Skoy ( APhA)
CDC Contributors
Amadea Britton (co -lead)
Michael Melgar (co -lead)
Lauren Roper
Fiona Havers
Chris TaylorMonica Patton
Rebecca Woodruff
Meredith McMorrow
Dave Wentworth
Diya Surie
Jennifer DeCuir
Mila Prill
Monica GodfreyRuth Link -Gelles
Amanda Payne
Danielle Moulia
Megan Wallace
Natalie ThornburgMelissa Coughlin
Jefferson Jones
Katherine Fleming -Dutra
Ismael Ortega Sanchez
Noelle Molinari
Pragna Patel
Aron Hall
Hannah RosenblumDerrell Powers
Raigan Wheeler
Jarrett Gartin
Trang Nguyen Wisard
Elizabeth Greene
Manisha Patel
Lisa Grohskopf
Anne HauseDavid Shay
Christine Olson
Tom Shimabukuro
Karen Broder
John HsuPedro Moro
Patricia WodiAndrew Leidner
Jamison Pike
Sarah Meyer
Elisha Hall
Nicole DowlingTara Anderson
9
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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. Adult Respiratory Syncytial Virus (RSV) Session Camille Kotton, MD Chair, Adult RSV Work Group Advisory Committee on Immunization Practices (ACIP) February 29, 2024 As a…


02 RSV Adults Das 508

© 2024 Moderna, inc. All rights reserved.Overview of Moderna’s
Investigational RSV Vaccine (mRNA-1345) in Adults ≥ 60 Years of Age
Advisory Committee on Immunization Practices (ACIP)
Rituparna Das, MD, PhD
Feb 29, 2024The safety and efficacy of this investigational RSV vaccine have
not been established in any country for any use
Outline of
PresentationOverview of mRNA- 1345, Moderna’s
investigational RSV vaccine
Pivotal Phase 2/3 trial
Efficacy
Safety
Immunogenicity
Persistence of antibody and revaccination –
 Phase 1 trial
Concomitant administration with influenza and
COVID- 19 vaccines
Summary
NE-3
Investigational RSV Vaccine (mRNA -1345) Designed to Encode
for a Stabilized Prefusion F Glycoprotein
•LNP encapsulated mRNA -based vaccine
encoding the RSV fusion (F) glycoprotein
stabilized in the prefusion conformation
•Prefusion F elicits potent neutralizing
antibody response1,2
•Antibodies to the F protein cross -react between RSV -A and RSV -B
•RSV vaccine uses the same LNP as
Moderna COVID -19 vaccines3
•Phase 1: mRNA -1345 is well tolerated with
persistent antibody levels through 12
months4
1. Crank et al. Science , 2019;  2. McKekkan et al. Science, 2013; 3. Aranda and Polack, Front Immunol , 2019; 4. Simorellis et al. ESWI  2023
NE-4
Pivotal Safety and Efficacy Trial of RSV Vaccine,
mRNA-1345 (Study 301)
NE-5
Study Design
Population
Healthy adults including those with chronic, stable medical conditions, and/or frailty
≥ 60 years of age
22 countries (both Northern and Southern Hemisphere)
Regimen and follow -up
Single-dose regimen (1:1 50 μg RSV vaccine or saline placebo)
24-month follow -up
Weekly active RSV case surveillance performed throughout study to addresses
unpredictability of RSV seasons following pandemic
Stratified by
Age (60 - 74 and ≥ 75 years)
Presence or absence of congestive heart failure or chronic  obstructive pulmonary
diseaseStudy 301
clinicaltrials.gov NCT05127434 https://clinicaltrials.gov/ct2/show/NCT05127434
NE-6
Enrollment Enriched for High -Risk Groups
Study 301
COPD
CHF
Asthma
Chronic respiratory disease1
Diabetes
Advanced liver disease
Advanced renal diseaseMeasured by Edmonton Frail Scale across 9 domains:
Cognition
General health status
Functional independence
Social support
Medication use
0-17 point scale
Fit (0 –3)
Vulnerable (4– 5)
Frail (6 -17)
Individuals with Comorbidities
 Frail Individuals
1 Chronic respiratory disease includes chronic pulmonary
fibrosis (idiopathic and otherwise), restrictive lung
disease, asbestosis, bronchiectasis, cystic fibrosis, pulmonary hypertension, sarcoidosis, and history of tuberculosisNutrition
Mood
Continence
Functional
performance
NE-7
Study Design – Randomization
Study 301
No safety signals identified after DSMB review of Phase 2 safety data
Allowed for seamless transition to start of Phase 3Adults
≥ 60 Years
N = 36,557
Clinicaltrials.gov NCT05127434 https://clinicaltrials.gov/ct2/show/NCT05127434
DSMB = Data Safety and Monitoring Board
Phase 2
United States
Initiated November 2021
N = 1,991
Phase 3
Global Sites
Initiated February 2022
N = 34,566
Investigational RSV Vaccine (mRNA -1345, 50 μg)
N = 993
Placebo
N = 998
Investigational RSV Vaccine (mRNA -1345, 50 μg)
N = 17,311
Placebo
N = 17,2551:1
1:1
NE-8
36,557 Participants Enrolled in 22 Countries
(as of April 30, 2023 data cutoff)
Study 301
Number of participants in each country shown in parentheses269 Study Sites Across Northern and Southern Hemisphere
Australia  (256)
Bangladesh (2,421)
Japan  (822)
New Zealand  (299)
Singapore  (8)
South Korea (27)
Taiwan  (84)
South Africa (982)Belgium  (413)
Finland (96)
Germany  (471)
Poland (346)
Spain (220)
United Kingdom (450) Canada  (706)
United States  (19,571)
Mexico  (733)
Argentina  (3,589)
Chile  (679)
Colombia  (2,625)
Costa Rica (208)
Panama  (1,551)Randomization Set
NE-9
Primary and Additional Efficacy Analyses
US 2021-2023 RSV Hospitalization Rates (RSV -NET) in Adults ≥ 65 Years1
*Median RSV hospitalization rate for 2016 – 2019. Data only collected from October to April each year.
1. CDC. Respiratory Syncytial Virus Hospitalization Surveillance Network (RSV -NET). https://data.cdc.gov/Public -Health- Surveilla nce/Weekly -Rates -of-Laboratory -Confirmed -RSV-Hospitali/29hc -
w46k/data_preview. 2. Wilson E, et al. NEJM. 2023;389:2233- 2244. RSV efficacy study
conducted across2021 – 2022 and
2022 – 2023 seasons
>50% of participants enrolled in US
Primary Analysis: Met success criteria
2
Additional Analysis: 94% of participants followed for ≥ 6 monthsOverall RSV
Hospitalization
Rate per
100,000 Adults
≥ 65 Years
01234567
2016 -2019
RSV Seasons*2021 -2022
RSV Season 2016 -2019
RSV Seasons*Additional  Analysis
November 2021 –  April 2023
Median 8.6 Months (range 0.5 – 17.7) Follow -upVaccination Period
November 2021 –  December 2022
Primary Analysis
November 2021 –  November 2022
Median 3.7 Months (range 0.5 - 12.6) Follow -up
2022 -2023
RSV Season
NE-10
Demographics of Study Participants
CharacteristicRSV Vaccine (mRNA -1345)
(N = 18,304)Placebo
(N = 18,253)
Median Age, years 67 67
Male, n (%) 9,376 ( 51%) 9,277 (51%)
Age Group, n (%)
60 – 69 Years 11,348 (62%) 11,301 (62%)
70 – 79 Years 5,512 (30%) 5,500 (30%)
≥ 80 Years 1,444 (8%) 1,452 (8%)
Race/Ethnicity, n (%)
White 11,318 (62%) 11,290 (62%)
Black or African American 2,210 (12%) 2,175 (12%)
Asian 2,014 (11%) 2,001 (11%)
American Indian or Alaska Native 907 (5%) 897 (5%)
Native Hawaiian or Other Pacific Islander 28 (0.2%) 19 (0.1%)
Hispanic / Latino Ethnicity 6,118 (33%) 6,169 (34%)Study 301
Age, gender, race, and ethnicity balanced between vaccine and placebo recipients
Race/ethnicity generally representative of US populationRandomization Set
NE-11
1. Chronic respiratory disease includes chronic pulmonary fibrosis (idiopathic and otherwise), restrictive lung disease, asbesto sis, bronchiectasis, cystic fibrosis,
    pulmonary hypertension, sarcoidosis, and history of tuberculosis
2. Based on 17- point Edmonton Frailty ScoreParticipants with Lower Respiratory Tract Disease (LRTD)
Risk Factors and Comorbidities of Interest
CharacteristicRSV Vaccine (mRNA -1345)
(N = 18,304)Placebo
(N =18,253)
CHF or COPD, n (%) 1,310 (7%) 1,316 (7%)
≥1 Comorbidity of Interest, n (%)
COPD, CHF, asthma, chronic respiratory disease1,
diabetes, advanced liver disease, advanced renal disease5,417 (30%) 5,316 (29%)
Frailty2, n (%)
Vulnerable (score of 4- 5) 2,852 (16%) 2,917 (16%)
Frail (score of 6- 17) 1,013 (6%) 1,033 (6%)Study 301
Randomization Set
Enrollment included those at highest risk of severe RSV
NE-12
Safety Data
Study 301
Safety Set –  April 30, 2023 data cutoff
Based on 6 months of follow -up for ~94% of participants
NE-13
Primary Safety Endpoints and Duration of Follow -up
Study 301
1. Neurologic events of interest include Guillain -Barre syndrome,
acute disseminated encephalomyelitis, Bell’s palsy, and seizuresActive Safety
SurveillanceSolicited Local and
Systemic Adverse
Reactions
Unsolicited Adverse Events
Medically Attended AEs, Serious AEs Including Death, AEs Leading to
Discontinuations
Adverse Events of Special Interest(including Myocarditis, Pericarditis, Thrombocytopenia, Neurologic Events
1, and Anaphylaxis )
7 Days 28 Days 24 months
(ongoing)
NE-14Solicited Local Reactions within 7 Days After RSV Vaccine vs
Placebo
Study 301 - Solicited Safety Set
55.9%
13.8%
2.0% 0.6%3.7%0.0%15.2%
6.1%
0%20%40%60%80%100%Injection
Site PainInjection Site
ErythemaInjection Site
SwellingAxillary Swelling
or Tenderness
<1%Grade 2
Grade 3Grade 1
RSV vaccine, n=18174; placebo, n=18102
For placebo, grade 2 erythema and grade 2 and grade 3 swelling were < 1%No grade 4 local adverse reactionsSafety Set
Mostly grade 1, onset day 1-2, median duration of 1 -2 days for RSV vaccinePlacebo RSV Placebo RSV Placebo RSV Placebo RSV
NE-15Solicited Systemic Reactions within 7 Days After RSV Vaccine vs
Placebo
Study 301 - Solicited Safety Set
2.8% 1.3%26.7%
18.8%30.8%
20.0%25.6%
14.4%21.7%
14.0%
7.0%5.3%11.6%
6.8%
0%20%40%60%80%100%Headache Fatigue Myalgia ArthralgiaNausea /
VomitingChills Fever
RSV vaccine, n=18174; placebo, n=18102
Grade 4 fever was reported (mRNA -1345 [n=29] and placebo [n=35]); no other categories reported any grade 4 reactionsSafety Set
Mostly grade 1, onset day 1-2, median duration of 1 -2 days for RSV vaccineGrade 2
Grade 3Grade 1
Placebo RSV Placebo RSV Placebo RSV Placebo RSV Placebo RSV Placebo RSV Placebo RSV
NE-16Unsolicited Adverse Events Within 28 Days After Injection,
Regardless of Relationship to Vaccine/Placebo
RSV Vaccine (mRNA -1345)
(N = 18,245)Placebo
(N = 18,184)
 All, n (%) 3,749 (21%) 3,412 (19%)
Serious 115 (0.6%) 111(0.6%)
Fatal 1(<0.1%) 6 (<0.1%)
Medically -Attended 1,606 (9%) 1,531 (8%)
Leading to Study Discontinuation 2(<0.1%) 11(<0.1%)
Severe/≥ Grade 3 129(0.7%) 135(0.7%)
Non- Serious 3,634 (20%) 3,301 (18%)
Any Adverse Event of Special Interest  (AESI) 3(<0.1%) 8(<0.1%)Study 301 - Solicited Safety Set
No imbalances in any categories between vaccine and placebo recipientsSafety Set
Based on April 30, 2023 cutoff
NE-17
Adverse Events of Special Interest (AESI)
Neurological Disorders
No cases of Guillain- Barre syndrome or acute disseminated
encephalomyelitis (ADEM)
No imbalance observed for other neurological disorders including Bell’s
palsy/facial paralysis
Cardiac Events
No imbalance observed in cardiac arrhythmias such as atrial fibrillation
No CEAC adjudicated cases of:
Acute myocarditis in vaccine recipients
Acute pericarditis in vaccine recipients with onset < 42 daysStudy 301
Safety Set
CEAC – Cardiac Event Adjudication Committee
 Based on April 30, 2023 cutoff
NE-18
Efficacy
Study 301
NE-19
Key Efficacy Endpoints
Study 301
Vaccine efficacy to prevent first episode of RSV -LRTD (Lower Respiratory Tract Disease)
between 14 days and 12 months post -injection
≥ 2 signs/symptoms
≥ 3 signs /symptoms
Primary Efficacy Objectives
Vaccine efficacy to prevent:
First episode of RSV -ARD (Acute Respiratory Disease) between 14 days and 12 months post -
injection
First hospitalization associated with RSV -ARD or RSV -LRTD between 14 days and 12 months
post-injection
Key Secondary Efficacy Objectives
Vaccine efficacy against RSV -LRTD with shortness of breath (a surrogate measure of more severe
disease)1, 2
Exploratory Endpoint
1. Falsey et al NEJM , 2005; 2. Panozzo et al ESWI , 2023
NE-20
Definitions of LRTD and ARD
Study 301
+
RT-PCR
Confirmed
 RSVRSV Lower Respiratory Tract Disease (LRTD)
New or Worsening of ≥ 2 or ≥ 3 of Signs/Symptoms for ≥ 24 Hours
RSV Acute Respiratory Disease (ARD)
New or Worsening of ≥ 1 Signs/Symptoms for ≥ 24 Hours
Sinus
PainHoarsenessStuffy
NoseTachypneaShortness
of BreathSputum
Production
Wheezing
Sore
ThroatRunny
NoseChills HypoxemiaFeverPleuritic
Chest PainCoughTachypneaShortness
of BreathSputum
Production Wheezing
and/or
rales and/or
rhonchiFever and/
or CoughHypoxemiaPleuritic
Chest Pain
LRTD cases are a subset of the ARD cases
RSV surveillance was conducted year-round throughout study follow-up
NE-21
Primary Analysis
Study 301
Per Protocol Analysis – November 30, 2022 data cutoff
NE-22Efficacy of mRNA -1345 Against RSV LRTD and RSV ARD
among Adults ≥ 60 Years
Study 301  - Per Protocol Analysis
Vaccine efficacy for primary and key secondary endpoints (median 3.7 months) met lower bound
of CI criterion (>20%)
Regulatory criteria for licensure metPrimary Analysis
1. Alpha adjusted CI: 95.88% for RSV LRTD ≥ 2 symptoms, 96.36% for RSV LRTD ≥ 3 symptoms, 95.0% for RSV ARD
Wilson et al. NEJM,  2023Cases, n (%)
RSV Vaccine
(mRNA- 1345)
(N = 17,572)Placebo
(N = 17,516)Vaccine Efficacy (%)
Based on Hazard Ratios1
RSV LRTD
≥ 2 symptoms9 (0.05%) 55 (0.31%)83.7%
(66.0%, 92.2%)
RSV LRTD
≥ 3 symptoms3 (0.02%) 17 (0.10%)82.4%
(34.8%, 95.3%)
RSV ARD 26 (0.15%) 82 (0.47%)68.4%
(50.9%, 79.7%)
NE-23
Vaccine Efficacy Against RSV -A and RSV-B by Endpoint
Numbers of Events
RSV Vaccine
(mRNA -1345)
(N = 17,572)Placebo
(N = 17,516)Vaccine Efficacy
(CI)
RSV LRTD
≥ 2 Symptoms Overall 9 55 83.7% (66.0, 92.2)
RSV-A 3 36 91.7% (73.0, 97.4)
RSV-B 6 19 68.5% (21.1, 87.4)
RSV LRTD≥ 3 Symptoms Overall 3 17 82.4% (34.8, 95.3)
RSV-A 1 10 90.0% (22.0, 98.7)
RSV-B 2 7 71.5% (-37.0, 94.1)
RSV-ARDOverall 26 82 68.4% (50.9, 79.7)
RSV-A 11 51 78.5% (58.8, 88.8)
RSV-B 15 31 51.7% (10.6, 73.9)Study 301 -  Per-Protocol Efficacy Set
-40 -20 0 20 40 60 80 100Primary Analysis
Efficacy was observed for both RSV -A and RSV -B
Fewer cases of LRTD ≥ 3 symptoms resulted in larger confidence intervals for both subtypesVaccine Efficacy, % (Adjusted CIs)
Wilson et al. NEJM , 2023
NE-24Vaccine Efficacy by Age, Comorbidities, and Frailty
Against RSV LRTD ≥ 2 Symptoms
Numbers of Events
RSV LRTD with ≥ 2 Symptoms RSV Vaccine
(mRNA -1345)
(N = 17,572)Placebo
(N = 17,516)Vaccine Efficacy
(CI)
Overall 9 / 17,572 55 / 17,516 83.7% (66.0, 92.2)
Age60 – 69 Years 8 / 11,168 33 / 11,118 76.0% (48.0, 88.9)
70 – 79 Years 1 / 5,440 22 / 5,416 95.4% (65.9, 99.4)
≥ 80 Years 0 / 964 0 / 982 –
ComorbiditiesNo Comorbidities 7 / 12,377 38 / 12,431 81.6% (58.8, 91.8)
≥ 1 Comorbidities 2 / 5,195 17 / 5,085 88.4% (49.9, 97.3)
Frailty StatusFit (0-3) 8 / 13,396 45 / 13,250 82.3% (62.5, 91.7)
Vulnerable/Frail (≥ 4) 0 / 3,781 6 / 3,858 100.0% (NE, 100.0)Study 301 - Per-Protocol Efficacy Set
-40 -20 0 20 40 60 80 100Primary Analysis
Vaccine Efficacy, % (Adjusted CIs)
Case splits favorable for mRNA -1345 with respect to age, comorbidities, and frailty
No cases observed in ≥ 80- year-olds
Wilson et al. NEJM, 2023; NE - nonestimable
Comorbidities include COPD, CHF, asthma, chronic respiratory disease, diabetes, advanced liver disease, advanced renal disease
NE-25
Cases, n (%)
RSV Vaccine
(mRNA -1345)
(N = 17,572)Placebo
(N = 17,516)Vaccine Efficacy (%)
Based on Hazard Ratios
(95% CI)
RSV-LRTD Associated
Shortness of Breath1,2 2 (0.01%) 15 (0.09%)86.7%
(41.9%, 97.0%)
Medically Attended RSV -LRTD
(≥ 2 Symptoms and ER/Urgent Care)0 5 (0.03%) NEEfficacy Against Severe (based on Shortness of Breath)
and Medically Attended LRTD Among Adults ≥ 60 Years
Study 301 - Post Hoc Analysis/Per Protocol Analysis
Post Hoc Analysis
Shortness of breath is a key driver of seeking a higher level of care1,2
Vaccine is efficacious in preventing shortness of breath associated with RSV -LRTD
Case split favorable for medically attended RSV -LRTD (ER/urgent care visits)
Based on Nov 30, 2022 cutoff; NE - nonestimable
1.Falsey et al NEJM, 2005; 2. Panozzo et al. ESWI , 2023
NE-26
Additional Analysis
Study 301
Per Protocol Analysis – April 30, 2023 data cutoff
NE-27Efficacy of mRNA -1345 Against RSV LRTD and RSV ARD
among Adults ≥ 60 Years
Study 301 - Per Protocol Analysis
Additional Analysis
Vaccine protection continues over a longer period (median 8.6 months) through high-transmission 2022/2023
RSV season
Lower bound of the confidence interval continued to exceed 20%Cases, n (%)
RSV Vaccine
(mRNA- 1345)
(N = 18,112)Placebo
(N = 18,045)Vaccine Efficacy (%)
Based on Hazard Ratios
(95% CI)
RSV LRTD
≥ 2 symptoms47 (0.26%) 127 (0.70%)63.3%
(48.7%, 73.7%)
RSV LRTD
≥ 3 symptoms19 (0.10%) 51 (0.28%)63.0%
(37.3%, 78.2%)
RSV ARD 86 (0.47%) 185 (1.03%)53.9%
(40.5%, 64.3%)
NE-28Cumulative Incidence Curve – Efficacy Against RSV
LRTD with ≥ 2 Symptoms among Adults ≥ 60 Years
Study 301 - Per-Protocol Efficacy Set
Data cutoff date: Apr 30, 2023; *based on hazard ratio Additional Analysis
Cumulative
Incidence
Rate
(%)
Time from Randomization (Months)Vaccine Efficacy *
(95% CI)
63.3%
(48.7%, 73.7%)
8.6 months median
follow -up (range
0.5-17.7 months)
Separation in curves observed early and  sustained through follow -up
mRNA -1345 18112 18040 17971 17886 17789 17355 17076 14191 10634 7534 5073 3474 2327
Placebo 18045 17940 17845 17735 17623 17185 16908 14060 10591 7460 5021 3442 23030.01.1
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0 1 2 3 4 5 6 7 8 9 10 11 12Placebo
RSV Vaccine
(mRNA -1345)
number at risk
NE-29
Vaccine Efficacy Against RSV -A and RSV-B by Endpoint
Numbers of Events
RSV Vaccine
(mRNA -1345)
(N = 18,112)Placebo
(N = 18,045)Vaccine Efficacy
(CI)
RSV LRTD
≥ 2 Symptoms Overall 47 127 63.3% (48.7, 73.7)
RSV-A 24 78 69.4%  (51.7, 80.6)
RSV-B 22 50 56.3%  (27.9, 73.5)
RSV LRTD
≥ 3 Symptoms Overall 19 51 63.0% (37.3, 78.2)
RSV-A 10 30 66.9%  (32.2, 83.8)
RSV-B 9 22 59.3%  (11.7, 81.3)
RSV-ARDOverall 86 185 53.9% (40.5, 64.3)
RSV-A 43 106 59.7%  (42.5, 71.7)
RSV-B 42 80 47.9%  (24.3, 64.1)Study 301 - Per-Protocol Efficacy Set
-40 -20 0 20 40 60 80 100
Vaccine Efficacy, % (Adjusted CIs)Additional Analysis
Efficacy was observed for both RSV -A and RSV -B
NE-30Vaccine Efficacy by Age, Comorbidities, and Frailty
Against RSV LRTD ≥ 2 Symptoms
Study 301 - Per-Protocol Efficacy Set
Case splits favorable for mRNA -1345 with respect to age, comorbidities, and frailty
Too few cases in ≥ 80- year-olds to assess efficacy Numbers of Events
RSV LRTD with ≥ 2 Symptoms RSV Vaccine
(mRNA -1345)
(N = 18,112)Placebo
(N = 18,045)Vaccine Efficacy
(CI)
Overall 47/18,112 127/18,045 63.3% (48.7, 73.7)
Age60 – 69 Years 31/11,219 77/11,170 60.1%  (39.5, 73.7)
70 – 79 Years 10/5,464 45/5,439 78.0%  (56.3, 88.9)
≥ 80 Years 6/1,429 5/1,436 NE
ComorbiditiesNo Comorbidities 31/12,751 76/12,796 59.5%  (38.5, 73.4)
≥ 1 Comorbidities 16/5,361 51/5,249 69.3%  (46.1, 82.5)
Frailty StatusFit (0-3) 37/13,417 104/13,274 65.0%  (49.0, 75.9)
Vulnerable/Frail (≥ 4) 9/3,817 17/3,884 46.5%  (-20.0, 76.2)
-40 -20 0 20 40 60 80 100
Vaccine Efficacy, % (95% CIs)Additional Analysis
NE - nonestimable
Comorbidities include COPD, CHF, asthma, chronic respiratory disease, diabetes, advanced liver disease, advanced renal disease
NE-31Efficacy Against Severe LRTD and Hospitalizations
Among Adults ≥ 60 Years
Cases, n (%)
RSV Vaccine (mRNA -
1345)
(N = 18,112)Placebo
(N = 18,045)Vaccine Efficacy  (%)
Based on Hazard Ratios
(95% CI)
RSV-LRTD Associated Shortness of
Breath1,211 (0.06%) 43 (0.24%)74.6%
(50.7%, 86.9%)
RSV LRTD with ≥ 2 Symptoms and
ER/Urgent Care5 (0.03%) 13 (0.07%)61.8%
(-7.35, 86.45)
Hospitalizations 0 (0%) 2 (0.01%) NEStudy 301 - Post Hoc Analysis/Per Protocol Analysis
Based on April 30, 2023 cutoff
NE -  nonestimable
1. Falsey  et al NEJM , 2005; 2. Panozzo et al ESWI , 2023  Shortness of breath is a key driver of seeking a higher level of care1,2
Vaccine is efficacious in preventing:
Shortness of breath associated with RSV -LRTD
Medically attended RSV -LRTD (ER/urgent care visits)
2 hospitalizations in placebo recipients (both >70 years with comorbid conditions [asthma]; both recovered)Additional Analysis
NE-32
Immunogenicity
Study 301
Immunogenicity Subset
NE-33
RSV-A
Assay
RSV-B
AssayNeutralizing Antibody Response by RSV Subtype –
Baseline and Day 29
Study 301 - Microneutralization Antibody (IU/mL)
1350 1305 14257246
1001,00010,000100,000
All Participants Baseline Day 29 Baseline Day 29
5.1-fold rise
(N = 333) (N = 1515)mRNA -1345
(50 µg)
Placebo
Participants had
baseline titers consistent with prior exposure to
RSV
One dose of 50 μg of
mRNA -1345 increased
titers by:
>8-fold for RSV -A
>5-fold for RSV -B2404 2417 255321475
1001,00010,000100,000
All Participants Baseline Day 29 Baseline Day 29
8.4-fold rise
GMT
IU/mL
(95% CI)
(N = 333) (N = 1515)Per Protocol Immunogenicity Set
GMT
IU/mL
(95% CI)
NE-34
RSV-B
AssayRSV-A
AssayNeutralizing Antibody Response by RSV Subtype and Age –
Baseline and Day 29
Study 301 – Microneutralization Antibody (IU/mL)
Per Protocol Immunogenicity Set
Baseline titers similar across age groups
Day 29 titers and fold rise are similar across age groups60–69 Years 70–79 Years  ≥ 80 Years
230922612
274720374
270621812
1001,00010,000100,000
Baseline Day 29 Baseline Day 29 Baseline Day 29
GMT
IU/mL
(95% CI)GMT
IU/mL
(95% CI)
9.8-fold rise
 7.5-fold rise
 8.1-fold rise
5.5-fold rise
 4.8-fold rise
 5.1-fold risemRNA -1345 (50 µg)
13537457
14987093
14167139
1001,00010,000100,000
Baseline Day 29 Baseline Day 29 Baseline Day 29(n = 619) (n = 618) (n = 671) (n = 671) (n = 223) (n = 222)
(n = 617) (n = 616) (n = 672) (n = 671) (n = 223) (n = 222)Age by Decade
NE-35
T-cell Responses Following Receipt of mRNA -1345
CRID- 001 Study - 15 Adults, 50- 75 Years Old
CD4+ T cells CD8+ T cells
•Vaccine elicits persistent CD4+ and CD8+ T -cell responses RSV- F antigen specific, Interferon -γ+ T-cells (intracellular cytokine staining assay)
NE-36Durability of RSV -A and RSV -B Neutralizing Antibody Response with
mRNA- 1345 and Revaccination
Study 101 – Adults 65- 79 Years
100100010000100000
0123 6 121314RSV-A Neutralizing Antibody
100100010000100000
0123 6 121314
RSV-B Neutralizing Antibody
GMT
(95% CI)
Study Month
Study Month•RSV-A and RSV -B neutralizing antibodies detectable at 12 months post- vaccination, 2-3 fold above baseline
•Revaccination at 12 months results in increase in GMT
•Revaccination at 1 and 2 years is being evaluated in Phase 3 studiesGMFR from Day 0 10.1 6.96.8 5.5 2.77.37.0
Study Month6.46.85.8 4.5 2.55.24.5
N = 14 -18 adults
Simorellis et al, ESWI  2023
NE-37
Concomitant Administration of RSV Vaccine
(mRNA1345) with Quadrivalent Influenza Vaccine (Afluria) or Bivalent COVID -19 Vaccine
(mRNA-1273.214)
Study 302, Parts A & B
NE-38
Study 302: Safety and Immunogenicity Study of Concomitant Administration
of mRNA- 1345 with Quadrivalent Influenza Vaccine (Afluria) or COVID -19
Bivalent Vaccine in Adults ≥ 50
Planned
Sample Size Randomized
RSV Vaccine PlaceboCOVID- 19
Bivalent Vaccine
RSV VaccineCOVID- 19
Bivalent VaccinePlacebo
COVID- 19
Bivalent VaccinePlacebo PlaceboPart B
Group 1
Group 2
Group 3RSV Vaccine Placebo
RSV VaccineQuadrivalent
Flu Vaccine
Quadrivalent
Flu VaccinePlacebo
Group 1
Group 2
Group 3Part ADay 1
Day 29420 2491
600 690
600 692
560 562
560 566
560 563
1.Due to randomization error, sample size lower than planned
NE-39
Comparison of Day 29 Geometric Mean Titer Ratio (GMR) – Concomitant vs
Nonconcomitant Administration of mRNA -1345 and Quadrivalent Influenza Vaccine
Antibody GMR (95% CI)
RSV-A Neutralizing Antibody (IU/mL) 0.81 (0.67, 0.97)
RSV-B Neutralizing Antibody (IU/mL) 0.85 (0.73, 1.00)
Influenza A/H1N1 Antibody 0.89 (0.77, 1.03)
Influenza A/H3N2 Antibody 0.97 (0.86, 1.09)
Influenza B/Phuket Antibody 0.91 (0.81, 1.02)
Influenza B/Washington Antibody 0.93 (0.82, 1.05)Study 302, Part A
0.5 1 1.5
All GMR non -inferiority criteria met (LB of the 2- sided 95% CI of GMR > 0.667)GMR  (95% CI)0.667
NE-40
Comparison of Day 29 Geometric Mean Titer Ratio (GMR) – Concomitant vs
Nonconcomitant Administration of mRNA -1345 and COVID -19 Bivalent Vaccine
Antibody GMR (95% CI)
RSV-A Neutralizing Antibody (IU/mL) 0.80 (0.70, 0.90)
RSV-B Neutralizing Antibody (IU/mL) 0.89 (0.79, 1.00)
COVID- 19 (Wuhan) (AU/ml) 0.96 (0.87, 1.06)
COVID- 19 (Omicron) (AU/ml) 1.01 (0.89, 1.14)Study 302, Part B
0.5 1 1.5
GMR  (95% CI)0.667
All GMR non -inferiority criteria met (LB of the 2- sided 95% CI of GMR > 0.667)
NE-41Solicited Local Reactions within 7 Days After mRNA -1345 Alone or
Co-administered with Quadrivalent influenza Vaccine (Afluria) in Adults ≥ 50
Study 302, Part A - Solicited Safety Set
mRNA -1345 + Afluria,  n= 678; mRNA -1345 + placebo, n= 249; Afluria + placebo;  n= 683
One grade 4 event (0.4%) of axillary swelling or tenderness in mRNA -1345 + placebo group
Mostly grade 1, onset day 1-2, median duration of 2 days for RSV + Flu Solicited Safety Set
48% 47%
26%
1% 1% 2% 2% 3%1%12%15%
9%
0%10%20%30%40%50%60%70%80%90%100%
mRNA
+ flumRNA
+ pboflu +
pbomRNA
+ flumRNA
+ pboflu +
pbomRNA
+ flumRNA
+ pboflu +
pbomRNA
+ flumRNA
+ pboflu +
pboInjection Site Pain Injection Site
ErythemaInjection Site
SwellingAxillary Swelling
or Tenderness
%Grade 1
Grade 2
Grade 3 + 4
RSV +
AfluriaAfluria +
PlaceboRSV +
PlaceboRSV +
AfluriaAfluria +
PlaceboRSV +
PlaceboRSV +
AfluriaAfluria +
PlaceboRSV +
PlaceboRSV +
AfluriaAfluria +
PlaceboRSV +
Placebo
NE-42Solicited Systemic Reactions within 7 Days After mRNA -1345 Alone or
Co-administered with Quadrivalent Influenza Vaccine in Adults ≥ 50
Study 302, Part A - Solicited Safety Set
Mostly grade 1, onset day 1-2, median duration of 2 days for RSV + Flu Solicited Safety Set
20% 21%14%9% 11%7% 9% 11%7%
0%20%40%60%80%100%
mRNA +
flumRNA +
pboflu + pbo mRNA +
flumRNA +
pboflu + pbo mRNA +
flumRNA +
pboflu + pbo3%7%2%23% 25%17%26% 25% 22% 24% 23%
14%
0%20%40%60%80%100%
mRNA +
flumRNA +
pboflu + pbo mRNA +
flumRNA +
pboflu + pbo mRNA +
flumRNA +
pboflu + pbo mRNA +
flumRNA +
pboflu + pboFever Headache Fatigue Myalgia
%
Arthralgia Nausea / Vomiting Chills
%Grade 1
Grade 2
Grade 3 + 4
mRNA -1345 + Afluria,  n= 678; mRNA -1345 + placebo, n= 249; Afluria + placebo;  n= 683
Grade 4 fever reported in  1 recipient of mRNA 1345+ placeboRSV +
AfluriaAfluria +
PlaceboRSV +
PlaceboRSV +
AfluriaAfluria +
PlaceboRSV +
PlaceboRSV +
AfluriaAfluria +
PlaceboRSV +
PlaceboRSV +
AfluriaAfluria +
PlaceboRSV +
Placebo
NE-43Solicited Local Reactions within 7 Days After mRNA -1345 Alone or
Co-administered with COVID -19 Bivalent Vaccine in Adults ≥ 50
Study 302, Part B - Solicited Safety Set
mRNA -1345 + COVID -19, n= 558; mRNA -1345 + placebo, n= 555; COVID -19 + placebo;  n= 557
No grade 4 eventsSolicited Safety Set
61%
54% 55%
3% 3% 3% 3% 3% 3%19%17% 15%
0%10%20%30%40%50%60%70%80%90%100%
rsv +
covidrsv +
pbocovid +
pborsv +
covidrsv +
pbocovid +
pborsv +
covidrsv +
pbocovid +
pborsv +
covidrsv +
pbocovid +
pboInjection Site Pain Injection Site
ErythemaInjection Site
SwellingAxillary Swelling
or Tenderness
%Grade 1
Grade 2
Grade 3
Mostly grade 1, onset day 1-2, median duration of 2 days for RSV + COVID -19
RSV +
COVID-19COVID-19
+ PlaceboRSV
+
PlaceboRSV +
COVID-19COVID-19
+ Placebo RSV
+
PlaceboRSV +
COVID-19COVID-19
+ PlaceboRSV
+
PlaceboRSV +
COVID-19COVID-19
+ PlaceboRSV
+
Placebo
NE-44Solicited Systemic Reactions within 7 Days After mRNA -1345 Alone or
Co-administered with COVID -19 Bivalent Vaccine in Adults ≥ 50
Study 302, Part B - Solicited Safety Set
Mostly grade 1, onset day 1-2, median duration of 2 days for RSV + COVID -19 Solicited Safety Set
35%
22%26%
10%7% 9%22%
13%17%
0%20%40%60%80%100%
mRNA +
flumRNA +
pboflu + pbo mRNA +
flumRNA +
pboflu + pbo mRNA +
flumRNA +
pboflu + pbo8%2% 3%32%27% 30%41%
30% 33%40%
27%31%
0%20%40%60%80%100%
mRNA +
flumRNA +
pboflu + pbo mRNA +
flumRNA +
pboflu + pbo mRNA +
flumRNA +
pboflu + pbo mRNA +
flumRNA +
pboflu + pboFever Headache Fatigue Myalgia
%
Arthralgia Nausea / Vomiting Chills
%Grade 1
Grade 2
Grade 3 + 4
mRNA -1345 + COVID -19 vaccine,  n= 558; mRNA -1345 + placebo, n= 555; COVID -19 vaccine + placebo;  n= 557
Grade 4 fever reported in 1 recipient of COVID -19 + placeboRSV +
COVID-19COVID-19
+ PlaceboRSV
+
PlaceboRSV +
COVID-19COVID-19
+ PlaceboRSV
+
PlaceboRSV +
COVID-19COVID-19
+ PlaceboRSV
+
PlaceboRSV +
COVID-19COVID-19
+ PlaceboRSV
+
Placebo
NE-45Safety Events of Interest – Study of Concomitant Administration of
mRNA- 1345 with Influenza or COVID -19 Vaccine
No reports of:
Deaths, SAEs, or AESIs as assessed as related by the investigator
Anaphylaxis
Guillain Barre Syndrome
Acute disseminated encephalomyelitis (ADEM)
Bell’s palsy/facial paralysis
Acute myocarditis or acute pericarditisStudy 302 A and B – Based on 6 Months Follow-up
Safety Set
NE-46
SUMMARY
NE-47
Vaccine efficacious; met all regulatory criteria for licensure
Continued to be efficacious through median 8.6 months follow -up
Shown to prevent severe RSV disease (based on analysis of shortness of breath
 and medically attended RSV -LRTD)Investigational RSV Vaccine (mRNA -1345)
Safety
Efficacy  Vaccine generally well tolerated in >19,500 individuals
No GBS, no ADEM, or other safety concerns
Strong humoral and cellular immune responses
Detectable through 12 months post -vaccination; boosting observed with 1- year
 revaccination
RSV-A & RSV -B nAb responses similar across age groups, including
 those ≥ 80 years old
Immunogenicity
Concomitant
Administration Pre-specified immunogenicity criteria met & and no new safety signals observed
with concomitant administration of mRNA -1345 with influenza vaccine or mRNA -
COVID -19 vaccineSummary
NE-48
THANK YOU! Investigators
Study site personnel
Laboratory personnel
Most importantly, the individuals who
participated in these trials

Summary: © 2024 Moderna, inc. All rights reserved.Overview of Moderna’s  Investigational RSV Vaccine (mRNA-1345) in Adults ≥ 60 Years of Age Advisory Committee on Immunization Practices (ACIP) Rituparna Das, MD, PhD Feb 29, 2024The safety and efficacy of this investigational RSV vaccine have  not been established in any country for any use    Outline of  PresentationOverview of mRNA- 1345, Moderna’s  investigational RSV vaccine Pivotal Phase 2/3 trial Efficacy Safety Immunogenicity Persistence of…