03 mening Schillie 508

GRADE/Evidence to Recommendations Framework (EtR)
for GSK Pentavalent (MenABCWY) Vaccine
Sarah F. Schillie, MD, MPH, MBA
Advisory Committee on Immunization Practices
October 24, 2024National Center for Immunization & Respiratory Diseases
1
Meningococcal Vaccine Recommendations
Routine schedule
–One MenACWY* dose at age 11 –12 years and a booster at age 16 years
–Two MenB** doses at age 16 –23 years (shared clinical decision -making [SCDM])
•Preferred age range: 16 –18 years
Increased risk, MenACWY*
–Asplenia, complement deficiency, complement inhibitor use, and HIV infection
–Some microbiologists
–Exposure during an outbreak
–Travel to hyperendemic areas
–First -year college students (if not previously vaccinated at age ≥16 years)
Increased risk, MenB**
–Asplenia, complement deficiency, and complement inhibitor use
–Some microbiologists
–Exposure during an outbreak
*MenACWY vaccines are interchangeable; **MenB vaccines are not interchangeable2
Two new MenABCWY vaccines:
–Pfizer (Penbraya, ACIP vote October 2023)
–GSK (ACIP vote anticipated February 2025)
Each vaccine is a combination of an existing:
–MenACWY vaccine
–MenB vaccine
Each vaccine assessed separately by Work Group
–Lack of data directly comparing Pfizer and GSK Pentavalent vaccinesPentavalent MenABCWY Vaccines
and
3
Pfizer and GSK MenABCWY Vaccines
Pfizer (Penbraya) GSK*
ACWY component Nimenrix (not licensed in U.S.) Menveo
B component Trumenba Bexsero
Schedule 2 doses, 6 months apart 2 doses, 6 months apart*
Age 10–25 years 10–25 years*
*Vaccine not yet licensed in U.S. and this slide represents anticipated schedule and age indications 4
Policy Questions
PICO 1:
Should the GSK pentavalent vaccine be included as an option for MenACWY/MenB
vaccination in people currently recommended to receive both vaccines at the same visit?
– For example, 16 year- olds*
PICO 2:
Should the GSK pentavalent vaccine be included as an option for people currently recommended to receive MenACWY only?
–For example, 11 –12 year -olds
PICO 3:
Should the GSK pentavalent vaccine be included as an option for people currently recommended to receive MenB only?
– For example, during a serogroup B outbreak
*16 year -olds who decide to receive the MenB vaccine based on shared clinical decision -making5
Combined Policy and PICO Questions
6Policy QuestionShould the pentavalent vaccine be included as an option for people currently
recommended to receive MenACWY and MenB, MenACWY only, or MenB only ?
PopulationAll individuals aged ≥10 years currently recommended to receive MenACWY+MenB,
MenACWY , or MenB vaccine
Intervention Vaccination with the pentavalent vaccine
Comparison Vaccination with currently licensed MenACWY+MenB, MenACWY , or MenB vaccine
Outcomes•Meningococcal disease caused by serogroups A, B, C, W, and Y
•Short- term immunity
•Persistent immunity
•Interference with other recommended vaccines administered concurrently
•Serious adverse events
•Non -serious adverse events
Outcomes Table
Outcome Importance* Included in
Evidence Profile
Meningococcal disease caused by serogroups
A, B, C, W, and YCritical Yes
Persistent immunity Important Yes
Short -term immunity Critical Yes
Interference with other recommended vaccines administered concurrentlyImportant Yes
Serious adverse events Critical Yes
Non -serious adverse events Important Yes
*Three options:  critical, important but not critical, of limited importance for decision making
7
How PICOs Translate into Schedule Options for
Healthy Adolescents
8OptionsDose at age
11—12 yearsDose at age
16 yearsDose at age
16 years
Standard of care (MenACWY only) Q Q -
Standard of care (MenACWY + MenB) Q Q+B B
PICO 1 (MenABCWY as option for MenACWY + MenB) Q P B
PICO 2 (MenABCWY as option for MenACWY) P P B
PICO 3 (MenABCWY as option for MenB) Q P P
Combination of all 3 PICOs P P P
Legend
Q = MenACWY (quadrivalent)
B = MenB
P = MenABCWY (pentavalent)
EtR Domain Question
Public health
problemIs invasive meningococcal disease a problem of public health
importance?
Benefits and
harmsHow substantial are the desirable anticipated effects?
How substantial are the undesirable  anticipated effects?
Do the desirable anticipated effects outweigh the undesirable effects?
What is the overall certainty of the evidence for the critical outcomes?
Values Does the target population feel the desirable effects are large relative
to the undesirable effects?
Is there important variability in how patients value the outcome?
Acceptability Is the intervention acceptable to key stakeholders?
Resource use Is the intervention a reasonable and efficient allocation of resources?
Equity What would be the impact of the intervention on health equity?
Feasibility Is the intervention feasible to implement?
9
Public health problem
Is invasive meningococcal disease a problem of public health importance?
Meningococcal Disease
Most often presents as meningitis or bacteremia
Progresses rapidly
10–15% of cases are fatal (even with appropriate antibiotic
therapy)
~20% of survivors experience long -term sequelae
–Cognitive deficits
–Hearing loss
–Limb amputations
11
Public Health Problem
Is invasive meningococcal disease a problem of public health importance?
No Probably
noProbably
yesYes VariesDon’t
know
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB  X
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB  X
12
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?
Studies Included in Review of Evidence
14Study ID(s) Location(s)Study
DesignPhase Blinding PopulationAuthor, year or
Study IDPeriod
NCT01210885
NCT01367158
NCT02451514Chile, Colombia,
PanamaRCT IIObserver -
blindHealthy, immuno -naïve individuals aged
11-18 yearsSaez -Llorens 2015a Dec 2010— Jul 2011
Saez -Llorens 2015b Jul 2011— Jul 2012
Open- label*Prior participants + individuals w/o
meningococcal vaccine historySaez -Llorens 2018 Jun 2015— Dec 2015
NCT01272180
NCT01992536Poland, USA RCT IIObserver -
blindHealthy, immuno -naïve individuals aged
10-25 yearsBlock 2015 Aug 2011— Sep 2012
Szenborn 2018 Dec 2013— Apr 2015
NCT02140762
NCT02285777USA RCT IIbObserver -
blindHealthy, immuno -naïve individuals aged
10-18 yearsWelsch 2018 May 2014— Jun 2015
NCT02212457
NCT02946386Finland, Poland RCT IIbObserver -
blindHealthy, immuno -naïve individuals aged
10-18 yearsVesikari 2021Aug 2014— Mar 2016
Nov 2016— Feb 2018
NCT03587207 Czechia RCT II Open- labelHealthy, immuno -naïve individuals aged
10-25 yearsBeran 2021 Jul 2018— Dec 2018
NCT04502693Australia, Canada,
Czechia, Estonia,
Finland, Turkey, USARCT IIIObserver -
blindHealthy individuals aged 10 -25 years w/o
history of meningococcal disease or
vaccinationv72_72 Aug 2020— Sep 2022
NCT04707391 Argentina, Australia,
Canada, USARCT IIIObserver -
blindHealthy individuals aged 15 -25 years
vaccinated with MenACWY ≥4 years prior
and w/o history of meningococcal diseaseMenABCWY_019 Jan 2021— Sep 2023
*This extension study did not randomize participants. All prior participants were given a single dose of MenABCWY, while all new ly enrolled participants were given two doses of MenABCWY.
Short- term immunity one month after one dose
MenABCWY vs MenACWY
Short -Term Immunity After One Dose for Healthy Persons
1If >1 study included, effects and confidence intervals derived from a random -effects meta -analysis are presented; if one study i ncluded, traditional Wald confidence intervals are presented.
2Includes potential conflicts of interest that are not factored into the grading of the certainty of evidence.
3Includes one study with concomitant administration of MenB; meta -analysis suggested no statistically significant subgroup differ ences.
4hSBA titers are the established correlate of protection for serogroup C meningococcal disease. This correlation is assumed to  extend to other serogroups, but direct evidence for these serogroups is limited. Goldschneider
et al. Human immunity to the meningococcus. I. The role of humoral antibodies. J Exp Med. 1969;129(6):1307 –26. 16Certainty assessment No. of patients Effect1
Certainty Importance No. of
studiesStudy
designRisk of
biasInconsistency Indirectness ImprecisionOther
considerations2GSK
MenABCWYComparatorRelative effect
RR (95% CI)Absolute effect
RD (95% CI)
per 100,000
Short -term immunity vs MenACWY (follow -up: 1 month) Serogroup  A
Moderate Critical
43 Randomized
trialsNot
seriousNot serious Serious4 Not serious GSK funded914 1,093 0.94 (0.86, 1.01)5,437 fewer (11,705
fewer to 832 more)
Serogroup C
926 1,105 1.03 (0.97, 1.10)2,726 more (2,545
fewer to 7,997 more)
Serogroup W
926 1,106 1.02 (1.00, 1.04)1,930 more (314 to
3,546 more)
Serogroup Y
929 1,109 0.98 (0.93, 1.03)1,930 fewer (6,528
fewer to 2,668 more)
Short -Term Immunity After One Dose for Persons at Increased Risk
1If >1 study included, effects and confidence intervals derived from a random -effects meta -analysis are presented; if one study i ncluded, traditional Wald confidence intervals are presented.
2Includes potential conflicts of interest that are not factored into the grading of the certainty of evidence.
3Includes one study with concomitant administration of MenB; meta -analysis suggested no statistically significant subgroup differ ences.
4hSBA titers are the established correlate of protection for serogroup C meningococcal disease. This correlation is assumed to  extend to other serogroups, but direct evidence for these serogroups is limited. Goldschneider
et al. Human immunity to the meningococcus. I. The role of humoral antibodies. J Exp Med. 1969;129(6):1307 –26.
5Studies did not include persons at increased risk.17Certainty assessment No. of patients Effect1
Certainty Importance No. of
studiesStudy
designRisk of
biasInconsistency Indirectness ImprecisionOther
considerations2GSK
MenABCWYComparatorRelative effect
RR (95% CI)Absolute effect
RD (95% CI)
per 100,000
Short -term immunity vs MenACWY (follow -up: 1 month) Serogroup  A
Low Critical
43 Randomized
trialsNot
seriousNot seriousVery
serious4,5 Not serious GSK funded914 1,093 0.94 (0.86, 1.01)5,437 fewer (11,705
fewer to 832 more)
Serogroup C
926 1,105 1.03 (0.97, 1.10)2,726 more (2,545
fewer to 7,997 more)
Serogroup W
926 1,106 1.02 (1.00, 1.04)1,930 more (314 to
3,546 more)
Serogroup Y
929 1,109 0.98 (0.93, 1.03)1,930 fewer (6,528
fewer to 2,668 more)
Short- term immunity one month after
series completion
Two doses of MenABCWY vs two doses of MenB
Short -Term Immunity After Series* Completion for Healthy Persons
19*MenABCWY and MenB given on a 0,6 month schedule
1If >1 study included, effects and confidence intervals derived from a random -effects meta -analysis are presented; if one study i ncluded, traditional Wald confidence intervals are presented.
2Includes potential conflicts of interest that are not factored into the grading of the certainty of evidence.
3Only one study included, therefore results are consistent by default.
4hSBA titers are the established correlate of protection for serogroup C meningococcal disease. This correlation is assumed to  extend to other serogroups, but direct evidence for these serogroups is limited. Goldschneider
et al. Human immunity to the meningococcus. I. The role of humoral antibodies. J Exp Med. 1969;129(6):1307 –26. Certainty assessment No. of patients Effect1
Certainty Importance No. of
studiesStudy
designRisk of
biasInconsistency Indirectness ImprecisionOther
considerations2GSK
MenABCWYComparatorRelative effect
RR (95% CI)Absolute effect
RD (95% CI)
per 100,000
Short -term immunity after series completion vs MenB series (follow -up: 1 month) fHbp
Moderate Critical
1Randomized
trialsNot
seriousNone3 Serious4 Not serious GSK funded738 707 1.01 (0.99, 1.04)1,300 more (896
fewer to 3,496 more)
NadA
734 707 0.98 (0.96, 1.00)1,800 fewer (3,526 to
74 fewer)
NHBA
738 711 0.98 (0.96,1.00)2,200 fewer (4,110 to
290 fewer)
PorA
709 684 0.91 (0.86, 0.96)7,300 fewer (11,560
to 3,040 fewer)
Short -Term Immunity After Series* Completion for Persons at Increased Risk
20*MenABCWY and MenB given on a 0,6 month schedule
1If >1 study included, effects and confidence intervals derived from a random -effects meta -analysis are presented; if one study i ncluded, traditional Wald confidence intervals are presented.
2Includes potential conflicts of interest that are not factored into the grading of the certainty of evidence.
3Only one study included, therefore results are consistent by default.
4hSBA titers are the established correlate of protection for serogroup C meningococcal disease. This correlation is assumed to  extend to other serogroups, but direct evidence for these serogroups is limited. Goldschneider
et al. Human immunity to the meningococcus. I. The role of humoral antibodies. J Exp Med. 1969;129(6):1307 –26.
5Studies did not include persons at increased risk.Certainty assessment No. of patients Effect1
Certainty Importance No. of
studiesStudy
designRisk of
biasInconsistency Indirectness ImprecisionOther
considerations2GSK
MenABCWYComparatorRelative effect
RR (95% CI)Absolute effect
RD (95% CI)
per 100,000
Short -term immunity after series completion vs MenB series (follow -up: 1 month) fHbp
Low Critical
1Randomized
trialsNot
seriousNone3 Very
serious4,5 Not serious GSK funded738 707 1.01 (0.99, 1.04)1,300 more (896
fewer to 3,496 more)
NadA
734 707 0.98 (0.96, 1.00)1,800 fewer (3,526 to
74 fewer)
NHBA
738 711 0.98 (0.96,1.00)2,200 fewer (4,110 to
290 fewer)
PorA
709 684 0.91 (0.86, 0.96)7,300 fewer (11,560
to 3,040 fewer)
Long -term immunity two years after series
completion
Two doses of MenABCWY vs two doses of MenB
Long -Term Immunity After Series* Completion for Healthy Persons
22Certainty assessment No. of patients Effect1
Certainty Importance No. of
studiesStudy
designRisk of
biasInconsistency Indirectness ImprecisionOther
considerations2GSK
MenABCWYComparatorRelative effect
RR (95% CI)Absolute effect
RD (95% CI)
per 100,000
Long -term immunity after series completion vs MenACWY (follow -up: 2 years)
0
Long -term immunity after series completion vs MenB (follow -up: 2 years fHbp
Low Important
1Randomized
trialsNot
seriousNone3 Serious4 Serious5 GSK funded70 119 1.46 (0.84, 2.54)8,000 more (4,379
fewer to 20,379 more)
NadA
72 121 0.90 (0.77, 1.06)8,000 fewer (20,228
fewer to 4,228 more)
NHBA
71 122 1.31 (0.86, 2.00)9,000 more (4,770
fewer to 22,770 more)
PorA
71 121 1.17 (0.61, 2.22)2,000 more (9,069
fewer to 13,069 more)
*MenABCWY and MenB given on a 0,6 month schedule
1If >1 study included, effects and confidence intervals derived from a random -effects meta -analysis are presented; if one study i ncluded, traditional Wald confidence intervals are presented.
2Includes potential conflicts of interest that are not factored into the grading of the certainty of evidence.
3Only one study included, therefore results are consistent by default.
4hSBA titers are the established correlate of protection for serogroup C meningococcal disease. This correlation is assumed to  extend to other serogroups, but direct evidence for these serogroups is limited. Goldschneider
et al. Human immunity to the meningococcus. I. The role of humoral antibodies. J Exp Med. 1969;129(6):1307 –26.
5Based on both the precision of the relative and absolute effects and the relatively small sample size
Long -Term Immunity After Series* Completion for Persons at Increased Risk
23Certainty assessment No. of patients Effect1
Certainty Importance No. of
studiesStudy
designRisk of
biasInconsistency Indirectness ImprecisionOther
considerations2GSK
MenABCWYComparatorRelative effect
RR (95% CI)Absolute effect
RD (95% CI)
per 100,000
Long -term immunity after series completion vs MenACWY (follow -up: 2 years)
0
Long -term immunity after series completion vs MenB (follow -up: 2 years fHbp
Very low Important
1Randomized
trialsNot
seriousNone3 Very
serious4,5 Serious6 GSK funded70 119 1.46 (0.84, 2.54)8,000 more (4,379
fewer to 20,379 more)
NadA
72 121 0.90 (0.77, 1.06)8,000 fewer (20,228
fewer to 4,228 more)
NHBA
71 122 1.31 (0.86, 2.00)9,000 more (4,770
fewer to 22,770 more)
PorA
71 121 1.17 (0.61, 2.22)2,000 more (9,069
fewer to 13,069 more)
*MenABCWY and MenB given on a 0,6 month schedule
1If >1 study included, effects and confidence intervals derived from a random -effects meta -analysis are presented; if one study i ncluded, traditional Wald confidence intervals are presented.
2Includes potential conflicts of interest that are not factored into the grading of the certainty of evidence.
3Only one study included, therefore results are consistent by default.
4hSBA titers are the established correlate of protection for serogroup C meningococcal disease. This correlation is assumed to  extend to other serogroups, but direct evidence for these serogroups is limited. Goldschneider
et al. Human immunity to the meningococcus. I. The role of humoral antibodies. J Exp Med. 1969;129(6):1307 –26.
5Studies did not include persons at increased risk
6Based on both the precision of the relative and absolute effects and the relatively small sample size
Adverse events
Serious
Non -serious after one dose
Non -serious after ≥2 doses
Serious Adverse Events Assessed as Possibly Related to Vaccination,
Regardless of Dosing Schedule
25StudyNumber
Pentavalent MenACWY MenB MenACWY/MenB
Saez -Llorens 201510 0 -- --
Block 2015 0 0 0 --
Welsch 2018 0 0 -- --
Vesikari 20212
(seizure, connective
tissue disorder)-- 0 --
Beran 2021 0 01
(syncope)0
v72_722 1
(neuromyelitis optica)1
(pyrexia)1
(ulcerative colitis)--
MenABCWY_019 0 0 -- --
1One related event during extension study in a recipient of a MenABCWY that contained ¼ of the usual OMV component
2These were reported as related to vaccination by investigators; however, they were not considered adverse drug reactions rela ted to vaccination after GSK and independent evaluation
Serious Adverse Events Assessed as Related to Vaccination for Healthy Persons and Those at Increased
Risk
26Certainty assessment No. of patients Effect1
Certainty Importance No. of
studiesStudy
designRisk of
biasInconsistency Indirectness ImprecisionOther
considerations2GSK
MenABCWYComparatorRelative effect
RR (95% CI)Absolute effect
RD (95% CI)
per 100,000
7Randomized
trialsNot
seriousNot serious Not serious Serious3GSK funded4,016
(0-2 events
per study)3,921
(0-2 events
per study)1.03 (0.30, 3.60)6 fewer (150 fewer
to 138 more)Moderate Critical
1If >1 study included, effects and confidence intervals derived from a random -effects meta -analysis are presented; if one study i ncluded, traditional Wald confidence intervals are presented
2Includes potential conflicts of interest that are not factored into the grading of the certainty of evidence.
3Based on the precision of the relative effect
4Studies did not include persons at increased risk.Certainty assessment No. of patients Effect1
Certainty Importance No. of
studiesStudy
designRisk of
biasInconsistency Indirectness ImprecisionOther
considerations2GSK
MenABCWYComparatorRelative effect
(95% CI)Absolute effect
RD (95% CI)
per 100,000
7Randomized
trialsNot
seriousNot serious Serious4Serious3GSK funded4,016
(0-2 events
per study)3,921
(0-2 events
per study)1.03 (0.30, 3.60)6 fewer (150 fewer
to 138 more)Low CriticalHealthy Persons
Persons at Increased Risk
The a pparent directional discrepancy between RR and RD is due to a continuity correction for the RR to adjust zeros
Non -Serious Adverse Events for Healthy Persons
27Certainty assessment No. of patients Effect1
Certainty Importance No. of
studiesStudy
designRisk of
biasInconsistency Indirectness ImprecisionOther
considerations2GSK
MenABCWYComparatorRelative effect
RR (95% CI)Absolute effect
RD (95% CI)
per 100,000
After one dose
4
Randomized
trialsNot
seriousvs MenB
Not serious Not serious Not serious GSK funded 2,766 2,315 1.00 (0.98, 1.02)106 more (1,434
fewer to 1,647 more)High Important
1vs MenB/MenACWY
None3 Not serious Serious4 GSK funded 100 204 0.93 (0.86, 1.00)6,588 fewer (13,337
fewer to 161 more)Moderate Important
6vs MenACWY
Not serious Not serious Serious5 GSK funded 2,683 1,190 1.97 (1.65, 2.36)42,626 more (36,291
to 48,962 more)Moderate Important
After two or more doses
2
Randomized
trialsNot
seriousvs MenB
Not serious Not serious Not serious GSK funded 1,680 2,660 1.00 (0.98, 1.02)135 more (1,837
fewer to 2,107 more)High Important
2vs MenACWY
Not serious Not serious Serious5 GSK funded 1,935 779 2.19 (1.89, 2.54)43,148 more (38,813
to 47,484 more)Moderate Important
1f >1 study included, effects and confidence intervals were derived from a random -effects meta -analysis; if  one study included, effect and confidence intervals were derived using the Wald method
2Includes potential conflicts of interest that are not factored into the grading of the certainty of evidence.
3Only one study included, therefore results are consistent by default.
4Based on the imprecision of the absolute effect and the relatively small sample size
5Based on the imprecision of the relative and absolute effects, despite the relatively large sample size.
Non -Serious Adverse Events for Persons at Increased Risk
28Certainty assessment No. of patients Effect1
Certainty Importance No. of
studiesStudy
designRisk of
biasInconsistency Indirectness ImprecisionOther
considerations2GSK
MenABCWYComparatorRelative effect
RR (95% CI)Absolute effect
RD (95% CI)
per 100,000
After one dose
4
Randomized
trialsNot
seriousvs MenB
Not serious Serious3Not serious GSK funded 2,766 2,315 1.00 (0.98, 1.02)106 more (1,434
fewer to 1,647 more)Moderate Important
1vs MenB/MenACWY
None4 Serious3 Serious5 GSK funded 100 204 0.93 (0.86, 1.00)6,588 fewer (13,337
fewer to 161 more)Low Important
6vs MenACWY
Not serious Serious3 Serious6 GSK funded 2,683 1,190 1.97 (1.65, 2.36)42,626 more (36,291
to 48,962 more)Low Important
After two or more doses
2
Randomized
trialsNot
seriousvs MenB
Not serious Serious3Not serious GSK funded 1,680 2,660 1.00 (0.98, 1.02)135 more (1,837
fewer to 2,107 more)Moderate Important
2vs MenACWY
Not serious Serious3 Serious6 GSK funded 1,935 779 2.19 (1.89, 2.54)43,148 more (38,813
to 47,484 more)Low Important
1f >1 study included, effects and confidence intervals were derived from a random -effects meta -analysis; if  one study included, effect and confidence intervals were derived using the Wald method
2Includes potential conflicts of interest that are not factored into the grading of the certainty of evidence.
3Studies did not include persons at increased risk.
4Only one study included, therefore results are consistent by default.
5Based on the imprecision of the absolute effect and the relatively small sample size
6Based on the imprecision of the relative and absolute effects, despite the relatively large sample size.
Summary of Evidence
PICO 1:  Certainty PICO 2:  Certainty PICO 3:  Certainty
Outcome Healthy Increased Risk Healthy Increased Risk Healthy Increased Risk
Critical outcomes
Meningococcal disease
caused by serogroups A, B,
C, W, and Y-- -- -- -- -- --
Short -term immunity Moderate Low Moderate Low Moderate Low
Serious adverse events Moderate Low Moderate Low Moderate Low
Important outcomes
Interference with other
recommended vaccines
administered concurrently-- -- -- -- -- --
Non -serious adverse
eventsModerate Low Moderate Low Moderate Low
Persistent immunity Low** Very low** -- -- Low Very low
*Three options:  critical, important but not critical, of limited importance for decision making; **MenB only 29
How substantial are the desirable  anticipated effects?Benefits and Harms
Minimal Small Moderate Large VariesDon’t
know
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX X X
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB  X
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB  X
30
How substantial are the undesirable  anticipated effects?Benefits and Harms
Minimal Small Moderate Large VariesDon’t
know
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX X
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB  X X
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB  X
31
Do the desirable effects outweigh the undesirable effects?Benefits and Harms
Favors
interventionFavors
comparisonFavors
bothFavors
neitherVariesDon’t
know
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX X X
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB  X X
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX X X
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB  X X X
32
What is the overall certainty of this evidence for the critical outcomes?Benefits and Harms:  Short -term Immunity
No studies
foundVery low Low Moderate High
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX X
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX X
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB  X X
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX X
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX X
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB  X X
33
What is the overall certainty of this evidence for the critical outcomes?Benefits and Harms:  Serious Adverse Events
No studies
foundVery low Low Moderate High
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX X
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX X
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB  X X
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX X
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX X
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB  X X
34
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?
MenACWY Coverage among Adolescents (2023)
≥ 1 dose
among 13 yr olds85.1%
≥ 2 doses
among 17 yr olds59.7%
Pingali  C et al. MMWR Morb Mortal Wkly Rep 2024.36
MenB Coverage among Adolescents (2023)
≥ 1 dose
among 17 yr olds32.4%
≥ 2 doses
among 17 yr olds12.8%
Pingali  C et al. MMWR Morb Mortal Wkly Rep 2024.37
Values
Most adolescents and parents prefer a simplified
meningococcal vaccine schedule (with fewer injections and fewer visits):
–89.6% of 16–23 year- olds
–69.1% of parents
Begum S et al. Infect Dis Ther 2024 (note GSK affiliation) 38
Values
Does the target population feel that the desirable effects are large relative to the
undesirable effects?
No Probably
noProbably
yesYes VariesDon’t
know
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB  X X
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB  X X X
39
Values
Is there important uncertainty about or variability in how much people value the
main outcome?
Important
uncertainty
or
variability Probably
important
uncertainty
or variabilityProbably
not
important
uncertainty
or variabilityNo
important
uncertainty
or variabilityNo known
undesirable
outcomes
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB  X
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX X
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX X
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB  X X
Acceptability
- Is the intervention acceptable to key stakeholders?
Combination Vaccines
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
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 2024 -27 Report of the Committee on Infectious Diseases. 33rd Edition.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
(MenB vaccine is more reactogenic than MenACWY vaccine)
42
Preference for Fewer Injections
Adolescents prefer fewer injections due to injection site
discomfort
Parents/caregivers prefer fewer injections to reduce number of physician visits
–Parental work loss
Begum S., et al. OFID ppS515- 6. IDWeek2023 (GSK affiliation). 43
Acceptability
Is the intervention acceptable to key stakeholders?
No Probably
noProbably
yesYes VariesDon’t
know
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX X
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX X
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB  X
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB  X X
44
Resource use
- Is the intervention a reasonable and efficient allocation of resources?
Economic Analysis
•PICO 1: Q-P-B was found to be cost -saving relative to the current
recommendation (vs. Q -Q-B-B).
•PICO 2: P-P-N could improve health outcomes, but costs $11.3
million per QALY saved (vs. Q -Q-N).
•PICO 3: Q-P-P is cost -saving compared to Q -Q-B-B.
Q-P-P is $4.5 million per QALY saved more than Q -P-B.
46
Resource Use
Is the intervention a reasonable and efficient allocation of resources?
No Probably
noProbably
yesYes VariesDon’t
know
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX X
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX X
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB  X X
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX X
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB  X*
*WG sentiment varied from no to yes 47
Equity
- What would be the impact on health equity?
Meningococcal Disease Incidence by Race―United
States, 2015–2023*
Source: NNDSS data with additional serogroup data from ABCs and state health departments. *2023 NNDSS data are preliminary.
Race is unknown for 5-12% of cases per year00.050.10.150.20.250.30.35
2015 2016 2017 2018 2019 2020 2021 2022 2023Incidence per 100,000
Year
White Black or African American American Indian or Alaska Native Asian or Pacific Islander
49
Average Annual Meningococcal Disease Incidence by Race
among 11 –20 year olds―United States, 2015–2023*
Source: NNDSS data with additional serogroup data from ABCs and state health departments. *2023 NNDSS data are preliminary.
Race is unknown for 6-15% of cases per year00.010.020.030.040.050.060.070.080.090.1
White Black or African
AmericanAmerican Indian or
Alaska NativeAsian or Pacific
IslanderIncidence per 100,000
50
Meningococcal Disease Incidence by Ethnicity ―
United States, 2015 –2023*
Source: NNDSS data with additional serogroup data from ABCs and state health departments. *2023 NNDSS data are preliminary.
Ethnicity is unknown for 2 -16% of cases per year00.020.040.060.080.10.120.140.16
2015 2016 2017 2018 2019 2020 2021 2022 2023Incidence per 100,000
Year
Hispanic or Latino Not Hispanic or Latino
51
Average Annual Meningococcal Disease Incidence by Ethnicity
among 11– 20 year olds―United States, 2015– 2023*
Source: NNDSS data with additional serogroup data from ABCs and state health departments. *2023 NNDSS data are preliminary.
Ethnicity is unknown for 3 -27% of cases per year00.010.020.030.040.050.060.070.080.09
Hispanic or Latino Not Hispanic or LatinoIncidence per 100,000
52
MenB Vaccine Availability
Counties with lower socioeconomic status (SES) had
fewer MenB doses stocked
–20 doses/100 adolescents for low SES counties
                   vs.
–28 doses/100 adolescents for high SES counties
Schley et al.  BMC Publ Hlth 2024 (note:  Pfizer affiliation)53
Equity and Shared Clinical Decision-Making
Provider or patient awareness of a SCDM recommendation is a pre-
requisite for discussions with patients and could lead to health
inequities
–Only 51% of pediatricians and 31% of family physicians reported always or
often discussing MenB vaccination
Pentavalent vaccine could potentially reduce disparities among those
who might be interested in MenB vaccination but who might not
receive clinical care that includes discussion of MenB vaccine
Gidengil et al. Vaccine 2023; Kempe et al. Pediatrics 2018.  54
Lack of MenB Vaccine Interchangeability
Lack of MenB vaccine interchangeability currently restricts
existing MenABCWY vaccine use to patients of providers stocking Pfizer MenB vaccine products
55
Equity
What would be the impact on health equity
ReducedProbably
reducedProbably
no impactProbably
increasedIncreased VariesDon’t
know
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX X
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX X X
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB  X
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX X
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB  X
56
Feasibility
- Is the intervention feasible to implement?
Feasibility
Challenges with insurance or financial burdens related
to pentavalent vaccine not expected
GSK pentavalent vaccine would provide additional option and may reduce number of doses for some people
Lack of MenB vaccine interchangeability complicates stocking considerations
58
Feasibility
Is the intervention feasible to implement?
No Probably
noProbably
yesYes VariesDon’t
know
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX X
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX X
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB  X X
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX X
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB  X
59
EtR Domain QuestionWork Group
Determination –
PICO 1Work Group
Determination –
PICO 2Work Group
Determination –
PICO 3
Public health
problemIs invasive meningococcal disease a problem of public health importance?Yes Yes Yes
Benefits and harmsHow substantial are the desirable anticipated effects? Small Small Small
How substantial are the undesirable anticipated effects? Minimal Small Minimal
Do the desirable anticipated effects outweigh the undesirable effects?Favors
interventionFavors intervention/
comparison/bothFavors
intervention/
comparison/both
What is the overall certainty of evidence? Low Low Low
Values Does the target population feel the desirable effects are large relative to the undesirable effects?Yes Probably yes Probably yes/yes/
don’t know
Is there important variability in how patients value the
outcome?Probably not/no Probably/probably
notProbably/probably
not
Acceptability Is the intervention acceptable to key stakeholders? Yes Probably yes Probably yes/yes
Resource use Is the intervention a reasonable and efficient allocation of
resources?Yes Probably no/varies Varies
Equity What would be the impact of the intervention on health equity?Probably
increasedProbably
increased/increasedProbably increased
Feasibility Is the intervention feasible to implement? Yes Probably yes/yes Yes
60
Balance of Consequences
Undesirable
consequences
clearly outweigh
desirable
consequences in
most settingsUndesirable
consequences
probably
outweigh
desirable
consequences in
most settingsThe balance
between
desirable and
undesirable
consequences is
closely balanced
or uncertainDesirable
consequences
probably
outweigh
undesirable
consequences
in most settingsDesirable
consequences
clearly
outweigh
undesirable
consequences
in most
settingsThere is
insufficient
evidence to
determine the
balance of
consequences
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX X
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB  X X X
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX X X
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB  X X X X
Work Group Interpretation
Is there sufficient information to move forward with a recommendation?
Yes No
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY +
MenBX
PICO 2 (PPB vs. QQBB or PP
vs. QQ):
MenABCWY vs. MenACWYX
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB  X
62
Work Group Interpretation
We do not
recommend the
interventionWe do
recommend the
intervention
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB  X X
63
64Comment Regarding Work Group Interpretation
Several Work Group members noted that it would be important to
harmonize recommendations between the GSK and Pfizer pentavalent
vaccines
–Unless there is a vaccine -specific reason to have a different
recommendation
65Next Steps
An interim recommendation for the GSK vaccine could mirror the
recommendation made for the Pfizer vaccine last year
–Accept PICO 1, reject PICOs 2 and 3
Recommendations for use of both pentavalent vaccines could then be
revisited as part of future adolescent schedule deliberations if desired
66Acknowledgements
Avnika Amin
Lucy McNamara
Xiaoyu Dong
Rebecca Morgan
Doug Campos -Outcalt
Noele Nelson
Susan Hariri
LeAnne Fox
Jennifer Collins
Amy Rubis
Thank you!
67For 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.

Summary: GRADE/Evidence to Recommendations Framework (EtR)  for GSK Pentavalent (MenABCWY) Vaccine Sarah F. Schillie, MD, MPH, MBA Advisory Committee on Immunization Practices October 24, 2024National Center for Immunization & Respiratory Diseases 1 Meningococcal Vaccine Recommendations  Routine schedule  –One MenACWY* dose at age 11 –12 years and a booster at age 16 years  –Two MenB** doses at age 16 –23 years (shared clinical decision -making [SCDM]) •Preferred age range: 16 –18 years  Increased…


04 mening Schillie 508

Introduction to MenB -4C (Bexsero) Interval and Dosing
Label Change
Sarah F. Schillie, MD, MPH, MBA
Advisory Committee on Immunization Practices
October 24, 2024National Center for Immunization & Respiratory Diseases
1
2MenB -4C (Bexsero) Interval Changes
Initially licensed by FDA under an accelerated approval
process
New immunogenicity data support changes to dosing schedule
–No safety concerns
Full FDA approval:  August 19, 2024
New dosing schedule aligned with MenB- FHbp
(Trumenba)
https://www.fda.gov/media/90996/download?attachment
https://wayback.archive -it.org/7993/20190423064853/https://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProduct s/UCM431447.pdf
3Previous Recommendations (Consistent with Label)
MenB -4C (Bexsero):  Previous MenB -FHbp  (Trumenba ):  Existing
Adolescents:
2-dose series (0, ≥1 month)Adolescents:  2-dose series (0, 6 month)
If dose 2 is administered earlier than 6 months,
administer 3
rd dose at least 4 months after dose 2
Persistent complement component deficiencies,
those with complement inhibitor use, functional or
anatomic asplenia, microbiologists routinely
exposed to Neisseria meningitidis , or persons
affected by an outbreak of serogroup B meningococcal disease:
2-dose series (0, ≥1 month)Persistent complement component deficiencies,
those with complement inhibitor use, functional or
anatomic asplenia, microbiologists routinely
exposed to Neisseria meningitidis , or persons
affected by an outbreak of serogroup B meningococcal disease:
3-dose series (0, 1 –2, 6 months)
3
4New MenB- 4C (Bexsero) Label
Two-dose schedule: Administer a dose (0.5 mL) at 0 and 6 months. If the
second dose is administered earlier than 6 months after the first dose, a
third dose should be administered at least 4 months after the second dose.
Three -dose schedule: Administer a dose (0.5 mL) at 0, 1 –2, and 6
months.
The choice of dosing schedule may depend on the risk of exposure and
the individual’s susceptibility to meningococcal serogroup B disease.
5Proposed ACIP Recommendations
Given the recent MenB- 4C (Bexsero) label change, ACIP will
vote for updated recommendations
Proposed recommendations will achieve alignment between
ACIP recommendations for MenB- 4C (Bexsero) and:
–FDA label
–ACIP MenB -FHbp  (Trumenba ) recommendations
Evidence to Recommendations
Framework (Abridged) for
MenB -4C (Bexsero) Interval and
Dosing Change
PICO Questions
PICO 1:
Among persons aged 16 –23 years recommended for MenB  vaccination based on
shared clinical decision -making, should MenB -4C be administered on a 0, 6 month
dosing interval, vs. a 0, ≥1 month dosing interval, for the prevention of invasive
meningococcal disease?
PICO 2:
Among persons with persistent complement component deficiencies, those with
complement inhibitor use, functional or anatomic asplenia, microbiologists routinely exposed to Neisseria meningitidis, or persons affected by an outbreak of serogroup B meningococcal disease , should MenB -4C be administered on a 0, 1 –2, 6 month
schedule, vs. a 0, ≥1 month schedule, for the prevention of invasive meningococcal disease?
7
PICO Questions
PICO 1:
Among persons aged 16 –23 years recommended for MenB  vaccination based on
shared clinical decision -making, should MenB -4C be administered on a 0, 6 month
dosing interval, vs. a 0, ≥1 month dosing interval, for the prevention of invasive
meningococcal disease?  ‘Yes‘ aligns with existing MenB -FHbp (Trumenba )
recommendation
PICO 2:
Among persons with persistent complement component deficiencies, those with
complement inhibitor use, functional or anatomic asplenia, microbiologists routinely exposed to Neisseria meningitidis, or persons affected by an outbreak of serogroup B meningococcal disease , should MenB -4C be administered on a 0, 1 –2, 6 month
schedule, vs. a 0, ≥1 month schedule, for the prevention of invasive meningococcal disease? ‘Yes‘ aligns with existing MenB -FHbp (Trumenba ) recommendation
8
Public health problem
Is invasive meningococcal disease a problem of public health importance?
10Meningococcal Disease
Most often presents as meningitis or bacteremia
Progresses rapidly
10–15% of cases are fatal (even with appropriate antibiotic
therapy)
~20% of survivors experience long -term sequelae
–Cognitive deficits
–Hearing loss
–Limb amputations
00.020.040.060.080.10.12
2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023Incidence per 100,000
YearB C Y W Other
Source: NNDSS data with additional serogroup data from Active Bacterial Core surveillance (ABCs) and state health departments
*2023 data are preliminaryTrends in Meningococcal Disease Incidence by
Serogroup – United States, 2006 –2023*
11
12Persons at Increased Risk for Serogroup B Meningococcal Disease
Estimated increased
riskEstimated
population size
Persistent complement component deficiency Up to 10,000 -fold 86,0001
Complement inhibitor use 2,000- fold 3,0002
Anatomic or functional aspleniaCase fatality -rate up
to 40 -70%>80,0003
Microbiologists routinely exposed to N. meningitidis 120- fold 100,0004
Persons exposed during an outbreak Up to 1,400- fold Up to ~33,000
Meningococcal Vaccination: Recommendations of the Advisory Committee on Immunization Practices, United States, 2020 | MMWR (c dc.gov)
1Estimated prevalence in all ages of 0.03% (Densen R. Clin Exp Immunol. 1991) though many may be undiagnosed.
2Preliminary estimate projected from 2017 claims data ( Marketscan and Medicaid)
3Based on estimated 100,000 persons with sickle cell disease (CDC data), minus the ~20,000 children aged <10 years with diseas e (estimated 1,800 -2,000 children identified with sickle cell disease annually
through newborn screening, with 95% survival to age 18 years).
4Bureau of Labor Statistics, 2016. Adjusted to estimate personnel with occupational exposure to N. meningitidis. https://www.b ls.gov/ooh/life -physical- and-social- science/microbiologists.htm#tab -1,
https://www.bls.gov/ooh/healthcare/medical- and-clinical- laboratory -technologists- and-technicians.htm
Meningococcal Disease Outbreaks 2022 -Present
Outbreak Outbreak Period Serogroup Cases (deaths)
Florida MSM December 2021 – February 2023 C 46 (9)
New York PEH February 2022 C 3
Florida College February – March 2022 B 3
Virginia Statewide June 2022 – Present Y 36 (8)*
Iowa Community November 2022 – July 2023 W 12 (2)
Ohio Amish Community December 2023 – January 2024 B 6†
Colorado PEH Jan 2024 – Present Y 6*
Oklahoma Correctional Facility March 2024 – May 2024 C 2 (1)
Kingdom of Saudi Arabia Travel April 2024 – Present W§ 14*
Abbreviation: MSM, men who have sex with men; PEH, people experiencing homelessness
*Ongoing
†5 additional suspect cases
§One additional serogroup C case and one additional nongroupable caseSlide provided by Amy Rubis13
14Is invasive meningococcal disease a problem of public health importance?Public Health Problem
No Probably
noProbably
yesYes VariesDon’t
know
PICO 1:
Healthy adolescents
 (0, 6 months)X
PICO 2:
Persons at increased risk
(0, 1– 2, 6 months) X
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?
16Comparators
0, 6 month schedule 0, 2, 6 month schedule
PICO 1 (healthy
adolescents)Dose 2 Dose 2
PICO 2 (persons at increased risk)-- Dose 3 vs. dose 2
CD-6V72_72: Solicited AEs within 7 Days after Vaccination with
MenB- 4C or MenACWYCRM
0%20%40%60%80%100%%Participants*Solicited Local AEs Solicited Systemic AEs
Injection-
site pain†Swelling‡Induration‡Erythema‡Fatigue†Headache†Myalgia†Arthralgia†Nausea† Fever§
Dose 1 2 1 2 1 2 1 2 1 2 1 2 1 2 1 2 1 2 1 2MenB -4C
0,6m
MenB -4C
0,2,6m
MenACWYCRM
(1 dose)
†Severity of symptom‡Size (mm)§Fever ( °C)
Mild – easily tolerated 25–50 38.0– 38.9
Moderate – interferes with normal activity 51–100 39.0– 39.9
Severe – prevents normal activity >100 ≥ 40.0
 Generally  mild-to-moderate  AE were reported following each vaccination
 Occurred at similar rates after the 1st, 2nd or 3rd dose of MenB -4C, and were higher than after vaccination with
MenACWYCRM
*Number of participants varies by study vaccination, 823- 835 for MenB -4C and 178 for MenACWY.
AE: Adverse Event
GSK, Data on File 2024N5550603 3 3 3 3 3 3 3 3 3
17
18How substantial are the desirable  anticipated effects?Benefits and Harms
Minimal Small Moderate Large VariesDon’t
know
PICO 1:
Healthy adolescents
 (0, 6 months)
PICO 2:
Persons at increased risk
(0, 1– 2, 6 months)
18
19How substantial are the desirable  anticipated effects?Benefits and Harms
Minimal Small Moderate Large VariesDon’t
know
PICO 1:
Healthy adolescents
 (0, 6 months)
PICO 2:
Persons at increased risk
(0, 1– 2, 6 months)
19
20How substantial are the desirable  anticipated effects?Benefits and Harms
Minimal Small Moderate Large VariesDon’t
know
PICO 1:
Healthy adolescents
 (0, 6 months)
PICO 2:
Persons at increased risk
(0, 1– 2, 6 months)
20
21How substantial are the desirable  anticipated effects?Benefits and Harms
Minimal Small Moderate Large VariesDon’t
know
PICO 1:
Healthy adolescents
 (0, 6 months)
PICO 2:
Persons at increased risk
(0, 1– 2, 6 months)
21
22How substantial are the desirable  anticipated effects?Benefits and Harms
Minimal Small Moderate Large VariesDon’t
know
PICO 1:
Healthy adolescents
 (0, 6 months)
PICO 2:
Persons at increased risk
(0, 1– 2, 6 months)
22
23How substantial are the desirable  anticipated effects?Benefits and Harms
Minimal Small Moderate Large VariesDon’t
know
PICO 1:
Healthy adolescents
 (0, 6 months)X
PICO 2:
Persons at increased risk
(0, 1– 2, 6 months) X X
24How substantial are the undesirable  anticipated effects?Benefits and Harms
Minimal Small Moderate Large VariesDon’t
know
PICO 1:
Healthy adolescents
 (0, 6 months)X X
PICO 2:
Persons at increased risk
(0, 1– 2, 6 months) X X
25Do the desirable effects outweigh the undesirable effects?Benefits and Harms
Favors
new
dosing
scheduleFavors
previous
dosing
scheduleFavors
bothFavors
neitherVariesDon’t
know
PICO 1:
Healthy adolescents
 (0, 6 months)X X
PICO 2:
Persons at increased risk
(0, 1– 2, 6 months) X
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?
MenB  Coverage among Adolescents (2023)
≥ 1 dose
among 17 yr olds32.4%
≥ 2 doses
among 17 yr olds12.8%
Pingali  C et al. MMWR Morb  Mortal Wkly  Rep 2024. 27
28Does the target population feel that the desirable effects are large relative to the
undesirable effects? Values
No Probably
noProbably
yesYes VariesDon’t
know
PICO 1:
Healthy adolescents
 (0, 6 months)X
PICO 2:
Persons at increased risk
(0, 1– 2, 6 months) X X
29Is there important uncertainty about or variability in how much people value the
main outcome? Values
Important
uncertainty
or
variability Probably
important
uncertainty
or variabilityProbably
not
important
uncertainty
or variabilityNo
important
uncertainty
or variabilityNo known
undesirable
outcomes
PICO 1:
Healthy adolescents
 (0, 6 months)X
PICO 2:
Persons at increased risk
(0, 1– 2, 6 months) X
Acceptability
- Is the intervention acceptable to key stakeholders?
31Harmonized Schedules
Harmonized dosing schedules for MenB- 4C (Bexsero) and
MenB- FHbp (Trumenba ) would likely be viewed favorably by
providers
32Extended Dosing Intervals
General Best Practice Guidelines for Immunization. https://www.cdc.gov/vaccines/hcp/acip- recs/general -recs/index.html
Meningococcal Vaccination: Recommendations of the Advisory Committee on Immunization Practices, United States, 2020 | MMWR (cdc. gov)   Doses administered at shorter- than -recommended intervals
can result in a sub- optimal immune response
–However, extended intervals prolong the time until one achieves protection
May be challenging for patients needing to complete vaccine
series prior to complement inhibitor therapy initiation
–Persons using complement inhibitors should complete or update vaccination
at least 2 weeks before complement inhibitor initiation unless the risks for delaying treatment outweigh the risks for developing meningococcal disease
33Persons Taking Complement Inhibitors
Among unvaccinated persons for whom complement inhibitor
therapy cannot be delayed, antimicrobial prophylaxis should be
administered alongside meningococcal vaccination and
continued for 2 weeks after vaccine administration
Persons taking complement inhibitors likely remain at
substantially increased risk for meningococcal disease, even if vaccinated and/or taking prophylaxis
Providers could consider continued antimicrobial prophylaxis
for the duration of complement inhibitor treatment
–Clinical judgement indicated
MMWR - Meningococcal Vaccination: Recommendations of the Advisory Committee on Immunization Practices, United States, 2020 (cdc. gov)
34Is the new dosing schedule acceptable to key stakeholders?Acceptability
No Probably
noProbably
yesYes VariesDon’t
know
PICO 1:
Healthy adolescents
 (0, 6 months)X
PICO 2:
Persons at increased risk
(0, 1– 2, 6 months) X
Resource use
- Is the intervention a reasonable and efficient allocation of resources?
36Number of Doses
Number of doses remains the same for most healthy
adolescents
–Unless 2nd dose administered earlier than 6 months after
1st dose
Additional dose required for at -risk populations
37Dose Price
Price per Dose
Bexsero (MenB -4C) Trumenba  (MenB -FHbp)
Private:
$223.746Private:
$190.26
Public pediatric:$150.026
Public adult:
$128.352Public pediatric:$135.97
Public adult:
$111.90 Harmonization with MenB- FHbp (Trumenba ) dosing
schedule could increase pricing competition
Current CDC Vaccine Price List | VFC Program | CDC
38Is the new dosing schedule a reasonable and efficient allocation of resources?Resource Use
No Probably
noProbably
yesYes VariesDon’t
know
PICO 1:
Healthy adolescents
 (0, 6 months)X
PICO 2:
Persons at increased risk
(0, 1– 2, 6 months) X
Equity
- What would be the impact on health equity?
40Schedules that require extended intervals or additional visits
could disproportionately affect populations with lower access to health care
–Unknown to what extent this would occurEquity
41Proportion Completing Series by Age 17 Years:
NIS-TEEN (2022)
%
Non -VFC eligible
MenB -4C (Bexsero) 49.6%
MenB -FHbp  (Trumenba ) 35.5%
VFC-eligible
MenB -4C (Bexsero) 51.4%
MenB -FHbp  (Trumenba ) 16.2%
42Proportion Completing Series by Age 19 Years:
Commercial Claims (2017- 2023)
%
Continuously -enrolled
MenB -4C (Bexsero) 67%
MenB -FHbp  (Trumenba ) 60%
43What would be the impact on health equityEquity
ReducedProbably
reducedProbably
no impactProbably
increasedIncreased VariesDon’t
know
PICO 1:
Healthy adolescents
 (0, 6 months)X X
PICO 2:
Persons at increased risk
(0, 1– 2, 6 months) X
Feasibility
- Is the intervention feasible to implement?
45Providers may need to make adjustments to their
practices (e.g., reminder/recall systems)
–Especially for providers who administer MenB  vaccine just prior to
college matriculation
Different manufacturers’ MenB vaccine products remain
not interchangeableFeasibility
46Is the new dosing schedule feasible to implement?  Feasibility
No Probably
noProbably
yesYes VariesDon’t
know
PICO 1:
Healthy adolescents
 (0, 6 months)X
PICO 2:
Persons at increased risk
(0, 1– 2, 6 months) X
Summary

48EtR Domain QuestionPICO 1:  WG
DeterminationPICO 2:  WG
Determination
Public health
problemIs IMD a problem of public health importance? Yes Yes
Benefits and harmsHow substantial are the desirable anticipated effects? Small Small/moderate
How substantial are the undesirable anticipated effects Minimal/small Minimal/small
Do the desirable anticipated effects outweigh the undesirable effects?Favors new schedule/favors bothFavors new schedule
Values Does the target population feel the desirable effects are large relative to the undesirable effects?Don’t know Don’t know/ probably yes
Is there important variability in how patients value the outcome?Probably not Probably not
Acceptability Is the intervention acceptable to key stakeholders? Probably yes Probably yes
Resource use Is the intervention a reasonable allocation of resources? Probably yes Probably yes
Equity What would be the impact of the intervention on health equity? Probably reduced/probably no impactProbably no impact
Feasibility Is the intervention feasible to implement? Yes Yes
49Balance of Consequences
Undesirable
consequences
clearly outweigh
desirable
consequences in
most settingsUndesirable
consequences
probably
outweigh
desirable
consequences in
most settingsThe balance
between
desirable and
undesirable
consequences is
closely balanced
or uncertainDesirable
consequences
probably
outweigh
undesirable
consequences
in most settingsDesirable
consequences
clearly
outweigh
undesirable
consequences
in most
settingsThere is
insufficient
evidence to
determine the
balance of
consequences
PICO 1:
Healthy adolescents
 (0, 6 months)X X X
PICO 2:
Persons at increased risk
(0, 1– 2, 6 months) X X
50Work Group Interpretation
Yes No
PICO 1:
Healthy adolescents
 (0, 6 months)X
PICO 2:
Persons at increased risk
(0, 1– 2, 6 months) XIs there sufficient information to move forward with a recommendation?
51Work Group Interpretation
PICO 1:
Should MenB -4C be administered on a 0, 6 month dosing interval, vs. a 0, ≥1 month
dosing interval, for the prevention of invasive meningococcal disease for persons
aged 16 –23 years recommended for MenB  vaccination based on shared clinical
decision -making?
We do not recommend the
interventionWe do recommend the
intervention
X
52Work Group Interpretation
PICO 2:
Should MenB -4C be administered on a 0, 1 –2, 6 month schedule, vs. a 0, ≥1 month
schedule, for the prevention of invasive meningococcal disease among persons with
persistent complement component deficiencies, those with complement inhibitor
use, functional or anatomic asplenia, microbiologists routinely exposed to Neisseria meningitidis, or persons affected by an outbreak of serogroup B meningococcal disease?
We do not recommend the
interventionWe do recommend the
intervention
X
53Proposal Language
ACIP recommends MenB -4C (Bexsero) be administered as a 2 -dose
series at 0 and 6 months when given to healthy adolescents and young
adults aged 16 –23 years based on shared clinical decision -making for the
prevention of serogroup B meningococcal disease
ACIP recommends MenB -4C (Bexsero) be administered as a 3 -dose
series at 0, 1–2, and 6 months when given to persons aged ≥10 years at increased risk for serogroup B meningococcal disease (i.e., persons with
anatomic or functional asplenia, complement component deficiencies, or
complement inhibitor use; microbiologists routinely exposed to N.
meningitidis  isolates; and persons at increased risk during an outbreak)
Summary and Work Group Considerations
Regarding MenB -4C (Bexsero)
 Interval and Dosing Change
55Summary
Proposed recommendations will align with updated FDA label for MenB -4C
(Bexsero)
–Harmonized with existing recommendations for MenB -FHbp (Trumenba )
Pros:
•New dosing schedules associated with increased immunogenicity compared to
previous schedule
•Harmonization between MenB -4C (Bexsero) and MenB -FHbp (Trumenba ) dosing
intervals and schedules likely to be viewed favorably by providers (although vaccines from different manufacturers remain not interchangeable)
Cons:
•Longer interval between doses increases the time to achieve vaccine- induced
protection and delays series completion
•Persons receiving complement inhibitor therapy may need prolonged antimicrobial prophylaxis due to extended time for vaccine series completion
56Proposed MenB -4C (Bexsero) Recommendations
Healthy adolescents and young adults (based on shared clinical decision-
making):
–2-dose series at 0 and 6 months
Persons aged ≥10 years at increased risk for serogroup B meningococcal
disease (i.e., persons with anatomic or functional asplenia, complement
component deficiencies, or complement inhibitor use; microbiologists routinely exposed to N. meningitidis  isolates; and persons at increased risk during an
outbreak):
–3-dose series at 0, 1 –2, and 6 months
57Proposal Language
ACIP recommends MenB -4C (Bexsero) be administered as a 2 -dose
series at 0 and 6 months when given to healthy adolescents and young
adults aged 16 –23 years based on shared clinical decision -making for the
prevention of serogroup B meningococcal disease
ACIP recommends MenB -4C (Bexsero) be administered as a 3 -dose
series at 0, 1–2, and 6 months when given to persons aged ≥10 years at increased risk for serogroup B meningococcal disease (i.e., persons with
anatomic or functional asplenia, complement component deficiencies, or
complement inhibitor use; microbiologists routinely exposed to N.
meningitidis  isolates; and persons at increased risk during an outbreak)
58Proposed CDC Clinical Considerations
No recommendation to recall persons previously
vaccinated at 0, ≥1 month
–Healthy adolescents
–Persons at increased risk
Persons should continue with booster vaccination
as previously recommended
59Proposed CDC Clinical Considerations, cont.
The 3 -dose series (doses administered at 0, 1– 2, 6
months) may be used to optimize rapid protection for
those who initiate the vaccine series less than 6 months
prior to period of increased risk
–e.g., when series initiation occurs within 6 months of college
matriculation
Would apply to MenB -4C (Bexsero) and MenB -FHbp
(Trumenba )
60CDC Clinical Considerations
 (currently recommended for MenB -FHbp [Trumenba ])
When administering the 2 -dose series (e.g., for healthy adolescents):
–If the second dose is administered <6 months after the first dose, a third dose should
be administered ≥4 months after the second dose (as per label)
–A second dose administered ≥6 months following the first dose is valid and does not need to be repeated
When administering the 3 -dose series (e.g., for persons at increased risk):
–A third dose is not needed if the second dose was administered ≥6 months after the
first dose
–If the third dose is administered <4 months after the second dose and <6 months
after the first dose, the dose should be repeated ≥ 4 months after the last dose
61Clinical Considerations, cont. (Unchanged)
MenB  vaccines from different manufacturers are not interchangeable
–All doses in a series, as well as booster doses, should be from the same manufacturer.
–If doses from both manufacturers have been administered to the same patient, the
patient should receive a complete series of either manufacturers’ product without counting doses of the other manufacturer as valid.
MenB -4C (Bexsero) may be administered simultaneously with other
vaccines
–MenB  vaccine should be administered in a separate limb from other vaccines
administered on the same clinic day, if feasible.
Contraindications:  Severe allergy to prior dose or component of vaccine
Precautions:  Pregnancy, moderate or severe acute illness
62Acknowledgements
Lucy McNamara
Amy Rubis
Gabrielle Cooper
Cheryl Isenhour
LeAnne Fox
Susan Hariri
Noele Nelson
Thank you!
63For 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.

Summary: Introduction to MenB -4C (Bexsero) Interval and Dosing  Label Change Sarah F. Schillie, MD, MPH, MBA Advisory Committee on Immunization Practices October 24, 2024National Center for Immunization & Respiratory Diseases 1 2MenB -4C (Bexsero) Interval Changes Initially licensed by FDA under an accelerated approval  process New immunogenicity data support changes to dosing schedule  –No safety concerns Full FDA approval:  August 19, 2024 New dosing schedule aligned with MenB- FHbp  …


01 RSV Adult Shaw 508

RSV Vaccination in Adults:
Introduction
Albert Shaw, MD, PhD
Chair, Adult RSV Work Group
Advisory Committee on Immunization Practices
October 24, 2024National Center for Immunization and Respiratory Diseases
2Adult RSV Work Group Membership
ACIP Voting Members
Albert Shaw (Chair)
Helen Chu
Mini Kamboj
Keipp Talbot
Ex Officio Members
Nicholas Geagan (FDA)
Nadine Peart Akindele (FDA)
Rachel Zhang (FDA)
Michelle Juaneza (HRSA)
Uzo Chukwuma (IHS)
Sonnie Kim (NIH/NIAID)CDC Co -Leads
Amadea Britton
Michael MelgarConsultants
Robert Atmar (Baylor College of Medicine)
Doug Campos -Outcalt (University of Arizona)
Peter Donofrio (Vanderbilt University)
Marie Griffin (Vanderbilt University)
Camille Kotton (Massachusetts General Hospital)
Cynthia Lucero (Veterans Health Administration)
Rebecca Morgan (Case Western Reserve University)
Tracy Ruckwardt (NIH/NIAID)
Jonathan Temte  (University of Wisconsin)Liaisons
Bindy Crouch (AIM)
April Killikelly (NACI, PHAC)
Gretchen LaSalle (AAFP)
Ruth Lynfield (NFID)
Steven Pergam (IDSA)
Kenneth Schmader (AGS)
Winnie Siu (NACI, PHAC)
Elizabeth Skoy ( APhA )
Vidya Sundareshan (ACP)
Katherine Williams (APTR)
3CDC Contributors
Melissa Coughlin
Fatima Dawood
Katherine Fleming -Dutra
Jarrett Gartin
Monica Godfrey
Aron Hall
Fiona Havers
Suzanne Heitfield
Michele Hlavsa
Jefferson Jones
Ruth Link -Gelles
Agustin Lopez
Josephine Mak
Meredith McMorrowNoelle -Angelique Molinari
Danielle Moulia
Ismael Ortega -Sanchez
Lakshmi Panagiotakopoulos
Pragna Patel
Monica Patton
Amanda Payne
Mila Prill
Lauren Roper
Melisa Shah
Diya Surie
Natalie Thornburg
Dennis Wang
Trang WisardImmunization Safety Office
Tarayn Fairlie
Julianne Gee
Anne Hause
Michael McNeil
Pedro Moro
Christine Olson
David Shay
John Su
Eric WeintraubImmunization Services Division
Erin Abramsohn
Janelle King
Andrew Leidner
Amy Parker Fiebelkorn
Jamison Pike
Influenza Division
Jill Ferdinands
Lisa GrohskopfNCIRD Office of the Director
Jessica MacNeil
Hannah Rosenblum
Melinda WhartonCoronavirus and Other Respiratory Viruses Division
4June 2024  ACIP Recommendations for RSV Vaccination
in Older Adults:
ACIP recommends all adults aged ≥75 years and adults aged 60 –74 years
who are at increased risk of severe RSV disease receive a single dose of RSV
vaccine.1,2
1. Recommendation is for any Food and Drug Administration –approved RSV vaccine ( Arexvy  [GSK];
Abrysvo  [Pfizer]; or mResvia  [Moderna]). There is no product preference.
2. Eligible adults are currently recommended to receive a single dose of RSV vaccine; adults who have
already received RSV vaccination should not receive another dose.
https://www.cdc.gov/mmwr/volumes/73/wr/mm7332e1.htm?s_cid=mm7332e1_w
5•Protein subunit (based on RSV F protein in prefusion conformation)
-GSK Arexvy1: monovalent RSV -A, AS01E adjuvant
-Pfizer Abrysvo2: bivalent RSV -A/RSV -B, no adjuvant
•Messenger RNA (mRNA, encoding RSV F protein in prefusion conformation)
-Moderna mResvia3: monovalent RSV -A, no adjuvantCurrent FDA -approved RSV vaccines
1. https://www.fda.gov/media/167805/download
2. https://www.fda.gov/media/168889/download
3. https://www.fda.gov/media/179005/download
6•Protein subunit
-GSK Arexvy1: monovalent RSV -A, AS01E adjuvant
-Pfizer Abrysvo2: bivalent RSV -A/RSV -B, no adjuvant
•mRNA
-Moderna mResvia3: monovalent RSV -A, no adjuvantCurrent FDA -approved RSV vaccines
Approved for prevention of
lower respiratory tract
disease (LRTD) caused by RSV
in adults aged ≥60 years
1. https://www.fda.gov/media/167805/download
2. https://www.fda.gov/media/168889/download
3. https://www.fda.gov/media/179005/download
7•Protein subunit
-GSK Arexvy1: monovalent RSV -A, AS01E adjuvant
-Pfizer Abrysvo2: bivalent RSV -A/RSV -B, no adjuvant
•mRNA
-Moderna mResvia3: monovalent RSV -A, no adjuvantCurrent FDA -approved RSV vaccines
Also approved for prevention
of LRTD caused by RSV in
adults aged 50 –59 years
who are at increased risk for
LRTD caused by RSV*
*There is no current ACIP
recommendation for RSV vaccination in
non-pregnant adults aged <60 years.1. https://www.fda.gov/media/167805/download
2. https://www.fda.gov/media/168889/download
3. https://www.fda.gov/media/179005/download
8•Protein subunit
-GSK Arexvy1: monovalent RSV -A, AS01E adjuvant
-Pfizer Abrysvo2: bivalent RSV -A/RSV -B, no adjuvant
•mRNA
-Moderna mResvia3: monovalent RSV -A, no adjuvantCurrent FDA -approved RSV vaccines
Also approved and
recommended for active
immunization of pregnant
individuals of any age* at
32–36 weeks gestational age
for the prevention of LRTD
and severe LRTD caused by
RSV in infants from birth
through 6 months of age.
1. https://www.fda.gov/media/167805/download
2. https://www.fda.gov/media/168889/download
3. https://www.fda.gov/media/179005/download*There is no current ACIP
recommendation for RSV vaccination in
non-pregnant  adults aged <60 years.
9•Protein subunit
-GSK Arexvy1: monovalent RSV -A, AS01E adjuvant
-Pfizer Abrysvo2: bivalent RSV -A/RSV -B, no adjuvant
•mRNA
-Moderna mResvia3: monovalent RSV -A, no adjuvantCurrent FDA -approved RSV vaccines
As of 10/22/244: also
approved for prevention of
LRTD caused by RSV in adults
aged 18 –59 years who are at
increased risk for LRTD
caused by RSV*
1. https://www.fda.gov/media/167805/download
2. https://www.fda.gov/media/168889/download
3. https://www.fda.gov/media/179005/download
4. https://www.pfizer.com/news/press -release/press -release -detail/us -fda-approves -pfizers -rsv-vaccine -abrysvor -adults -aged -18*There is no current ACIP
recommendation for RSV vaccination in
non-pregnant  adults aged <60 years.
10•No vote at today’s meeting
•Since June, the Work Group has been reviewing updated data relevant
to current recommendations and discussing potential policy options for
an RSV vaccination recommendation in adults aged <60 years
•Today, ACIP will see presentations from FDA, as well as manufacturer
presentations with updates on co -administration, duration of protection,
and immunogenicity in adults with immune compromise
•The Work Group will share interpretations regarding these updates and
considerations for future policy Today’s meeting
11Agenda: Thursday October 24, 2024
•Manufacturer presentation: mResvia  (Moderna) coadministration
with high -dose influenza vaccine
•Manufacturer presentation: Abrysvo  (Pfizer) immunogenicity in
immunocompromised adults and coadministration with COVID -19
and influenza vaccines
•Manufacturer presentation: Arexvy  (GSK) season 3 update on
safety, efficacy and immunogenicity in solid organ transplant
recipients
•Evaluation of Guillain -Barré Syndrome (GBS) following protein
subunit RSV vaccination among adults 65 years and older

•Work Group interpretations

•ACIP open discussion and questions  •Dr. Rituparna Das (Moderna)
•Dr. Iona Munjal (Pfizer)
•Dr. Susan Gerber (GSK)
•Dr. Patricia Lloyd (FDA)
•Dr. Michael Melgar (CDC)
For more information, contact CDC
1-800-CDC-INFO (232 -4636)
TTY:  1 -888-232-6348    www.cdc.gov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position
of the Centers for Disease Control and Prevention.

Summary: RSV Vaccination in Adults: Introduction Albert Shaw, MD, PhD Chair, Adult RSV Work Group Advisory Committee on Immunization Practices October 24, 2024National Center for Immunization and Respiratory Diseases 2Adult RSV Work Group Membership ACIP Voting Members Albert Shaw (Chair) Helen Chu Mini Kamboj Keipp Talbot  Ex Officio Members Nicholas Geagan (FDA) Nadine Peart Akindele (FDA) Rachel Zhang (FDA)  Michelle Juaneza (HRSA) Uzo Chukwuma (IHS) Sonnie Kim (NIH/NIAID)CDC Co -Leads Amadea…


02 RSV Adult Das 508

© 2024 Moderna, inc. All rights reserved.RSV Vaccine ( mRESVIA , mRNA -1345)
Concomitant Administration Overview
Advisory Committee on Immunization Practices
Rituparna Das, MD PhD
Oct 24, 2024
1
© 2024 Moderna, inc. All rights reserved.
Cumulative Burden of Seasonal Respiratory Viruses in US Older Adults
RSV Influenza2
Cumulative US
Hospitalization Rate
(≥65 yr, rate/100,000, 9/28/2024)1 227 106
US Vaccine Coverage
2023 -242-4
(COVID -19 & Flu ≥65 yrs, RSV ≥60 yrs)70% 23%
1.CDC RESP -NET, MMWR week 39, week ending 9/28/2024, https://www.cdc.gov/resp -net/dashboard/index.html  accessed 10/18/2024 ; 2. CDC COVIDVaxView
https://www.cdc.gov/covidvaxview/  ; 3. CDC FluVaxView  https://www.cdc.gov/covidvaxview/  ; 4. CDC RSVVaxView https://www.cdc.gov/rsvvaxview/  5. Bonanni et al
Human Vaccines Immuno 2023; 6. NVAC Pediatrics. 2003;. 7. https://www.cdc.gov/vaccines/hcp/acip -recs/general -recs/timing.html#ref -13; 8. Britton et al. MMWR 2024
https://www.cdc.gov/mmwr/volumes/73/wr/mm7332e1.htmCOVID -19
811
39%
Concomitant administration of vaccines is an effective method to increase vaccine coverage.
MMWR: Coadministration of RSV vaccines with other adult vaccines during the same visit is
acceptable5-8
© 2024 Moderna, inc. All rights reserved.
mRNA 1345 Clinical Development
NCT05127434, NCT05330975, NCT060604573
Adults ≥60 years
Study 301
Efficacy, Immunogenicity, Safety, and Correlate of Protection
Concomitant Administration
with Standard Dose Influenza
Adults ≥50 years
Study 302 - Part B
Concomitant Administration
with COVID -19
Adults ≥65 years
Study 304
Concomitant Administration
with High Dose Influenza
Adults ≥50 years
Study 302 - Part A
© 2024 Moderna, inc. All rights reserved.
Summary of Today’s Presentation4
1. ACIP, Feb 2024 Study 302 Parts A & B – Supports coadministration of mRNA -1345 with standard dose influenza and
COVID -19 vaccines (previously presented)1
•Well tolerated with no safety concerns
•Robust immunogenicity observed for all influenza strains, COVID -19, and RSV
Study 304 – Data for coadministration of mRNA -1345 with high -dose influenza vaccine
•Well-tolerated with no safety concerns
•Robust immunogenicity observed for all influenza strains and RSV
•RSV titers lower with coadministration; data from correlate of protection model demonstrate
that clinical efficacy against RSV disease, including severe disease, is likely maintained
Overall, the benefit: risk of coadministration of mRNA -1345 with standard and high -dose influenza
vaccines, and COVID -19 vaccine is positive
© 2024 Moderna, inc. All rights reserved.
RSV Case Accrual and Efficacy Analyses through 3 Seasons
in the Phase 2/3 Pivotal Trial
Study 3015
012345678910
1. CDC. Respiratory Syncytial Virus Hospitalization Surveillance Network (RSV -NET). https://www.cdc.gov/respiratory -viruses/data -research/dashboard/most -
impacted -hospitalizations.html  2. Based  on final FDA Package InsertOverall US
2021 -2023 RSV
Hospitalization
Rate per
100,000 Adults
≥ 65 Years1
2021 -2022
RSV Season 1Durability through
Season 2
Nov ‘21 – Apr ‘23Primary Analysis
Nov ‘21 – Nov ’22
2022 -2023
RSV Season 2Durability through
Season 3
Nov ‘21 – Mar ‘24
2023 -2024
RSV Season 3
2021 2022 2023 2024LRTD 2+
Cases
85 78.7%
174Efficacy2
50.3%
(37.5%, 60.7%)56.7%
33.1%, 72.6%)LRTD 2+Severe RSV
(shortness of
breath)
62.5%
(47.7%, 73.1%)74.6%
(50.7%, 86.9%)78.7%
(62.8%, 87.9%)86.7%
(41.9%, 97.0%)
338
© 2024 Moderna, inc. All rights reserved.
Predicted Efficacy
•Coadministration efficacy
•Revaccination efficacy
INPUT from Phase 3 Pivotal Efficacy Trial
(Study 301)RSV Correlate of Protection Model
Preplanned case -cohort design6
1597
mRNA -1345
Recipients
533
Placebo
Recipients
271
RSV ARD
Cases1
OUTPUT
•Day 1 and Day 29 sera collected from all study participants
•Evaluated for RSV -A and B neutralizing titers, and Pre -F binding titers
•Objective to determine the relationship between immunogenicity and efficacy to identify
correlates of protection
1.Includes 174 LRTD2+ and 70 LRTD3+ RSV cases; Ma, C et al, RSVVW, 2024
© 2024 Moderna, inc. All rights reserved.
Correlate of Risk Antibodies are a Correlate of Risk and Correlate of
Protection for RSV
Study 301 – LRTD2+ RSV Efficacy7
The panels demonstrate the Correlate of Risk  (A) and Correlate of Protection (B) analysis for the RSV -LRTD 2+ endpoint by Day 29 RSV -A neutralizing antibody.
A.The red and blue solid curves demonstrate the point estimate of the predictive risk for vaccine and placebo recipients at eac h assigned antibody titer. The red and blue dashed curves along with the
shaded area represent the bootstrap point -wise 95% confidence interval (CI).
B.The solid black curve shows the point estimate of controlled vaccine efficacy at each assigned antibody titer and the dashed curves demonstrate the bootstrap point -wise 95% CI.
102 103 104 105
Day 29 RSV -A Neutralizing Antibody Titer
(IU/mL)Probability
of RSV0.035
0.030
0.025
0.020
0.010
0.0050.015RSV-A Neutralizing Antibody
mRNA -1345 50 g
PlaceboCorrelate of Protection
102 103104 105
Day 29 RSV -A Neutralizing Antibody Titer
(IU/mL)Estimated
Vaccine
Efficacy1.0
0.8
0.6
0.2
00.4
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Concomitant Administration
of mRNA -1345 with High -Dose
Influenza Vaccine
Study 3048
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Study Design – Concomitant Administration of
mRNA -1345 & Fluzone HD
Study 304 - Phase 3, Randomized, Observer -Blind Trial
United States
Day 22Day 1
Stratified by age: 65–74 and ≥75 years (20%)
Study duration: ~8 months per participantFluzone HD +
mRNA -1345 Fluzone HD +
Placebo
Placebo mRNA -1345Vaccine
RegimenGroup 2
(Sequential administration)1:1 Randomization
~1900 adults ≥65 years of age
Group 1
(Concomitant administration)9
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110100100010000100000
Baseline Day 22 Baseline Day 22Concomitant Administration Results in Robust RSV and
Influenza Responses Across All Adults ≥65 Years
Study 304
GMT; Geometric Mean TiterGroup 1
D1: Flu HD + mRNA -1345
D22: PlaceboGroup 2
D1: Flu HD + Placebo
D22: mRNA -1345
Group 1 Group 2GMT
(95% CI)10
RSV-A Neutralizing Antibody Influenza A/H3N2, HAI
1101001000
Baseline Day 22 Baseline Day 22
Group 1 Group 2
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Co-Primary Immunogenicity Endpoint Evaluation
GMR  (95% CI)
Influenza A/H1N1 0.87 (0.78, 0.98)
Influenza A/H3N2 0.87 (0.78, 0.97)
Influenza B/Austria 0.89 (0.81, 0.98)
Influenza B/Phuket 0.95 (0.87, 1.03)
RSV-A 0.63 (0.57, 0.69)
RSV-B 0.64 (0.58, 0.70)Study 304
0 0.2 0.4 0.6 0.8 1 1.2
GMR (95% CI)11
GMR for all influenza strains close to 1; RSV GMRs lower, potential for clinical impact on efficacy will
 be discussed
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Correlation of Protection Suggests RSV Vaccine Efficacy Maintained
with Concomitant Administration of mRNA -1345 and Fluzone HD
Study 304  – Adults ≥65 Years
No statistical difference in predicted vaccine efficacy; point estimates were similarAntibody Treatment Group1 Day 22 GMT RSV-LRTD 2+ RSV-LRTD 3+
RSV-A
(IU/mL)Coadministration 11,57070%
(54, 84)86%
(70, 96)
Sequential Administration 19,20377%
(64, 87)88%
(75, 97)
RSV-B
(IU/mL)Coadministration 4,03669%
(51, 83)86%
(69, 97)
Sequential Administration 6,87673%
(58, 85)88%
(73, 97)
1. Concomitant administration: Fluzone  HD + mRNA -1345 at Day 1;  Sequential Administration: Fluzone  HD + placebo at Day 1,  mRNA -1345 at Day 22
Correlate of protection model based on ≥ 65 yr olds in study 301 to be consistent with age of study 304 participants 0% 20% 40% 60% 80% 100% 0% 20% 40% 60% 80% 100%
Predicted Vaccine Efficacy
(95% CI)Predicted Vaccine Efficacy
(95% CI)12
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Concomitant Administration of mRNA -1345 and Fluzone HD
Well Tolerated with No Safety Concerns Identified
•Concomitant administration well tolerated
•Predominantly mild events
•1-3 days duration
•Reassuring safety profile:
•No Guillain -Barre Syndrome (GBS)
•No acute disseminated encephalomyelitis (ADEM)
•No anaphylaxis
•No thrombocytopenia
•No cases of acute myocarditis or acute pericarditis Study 304
CEAC – Cardiac Event Adjudication Committee13
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Concomitant Administration of
mRNA -1345 with Standard Dose
Influenza and COVID -19
Vaccines
Study 302, Parts A & B14
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Antibody GMR (95% CI)
Influenza A/H1N1 0.89 (0.77, 1.03)
Influenza A/H3N2 0.97 (0.86, 1.09)
Influenza B/Phuket 0.91 (0.81, 1.02)
Influenza B/Washington 0.93 (0.82, 1.05)
RSV-A Neutralizing  0.81 (0.67, 0.97)
RSV-B Neutralizing 0.85 (0.73, 1.00)Comparable Immunogenicity with Concomitant vs Nonconcomitant
Administration of mRNA -1345 and Standard Dose Influenza  Vaccine
Study 302, Part A
0 0.2 0.4 0.6 0.8 1 1.2
GMR  (95% CI)15
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Comparable Immunogenicity with Concomitant vs Nonconcomitant
Administration of mRNA -1345 and COVID -19 Bivalent Vaccine
Study 302, Part B
Antibody GMR (95% CI)
COVID -19 (Wuhan) 0.96 (0.87, 1.06)
COVID -19 (Omicron) 1.00 (0.89, 1.14)
RSV-A Neutralizing  0.80 (0.70, 0.90)
RSV-B Neutralizing  0.89 (0.79, 1.00)
0 0.2 0.4 0.6 0.8 1 1.2
GMR  (95% CI)16
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Summary17
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Summary of Today’s Presentation18
1. ACIP, Feb 2024 Study 302 Parts A & B – Supports coadministration of mRNA -1345 with standard dose influenza and
COVID -19 vaccines (previously presented)1
•Well tolerated with no safety concerns
•Robust immunogenicity observed for all influenza strains, COVID -19, and RSV
Study 304 – Data for coadministration of mRNA -1345 with high -dose influenza vaccine
•Well-tolerated with no safety concerns
•Robust immunogenicity observed for all influenza strains and RSV
•RSV titers lower with coadministration; data from correlate of protection model demonstrate
that clinical efficacy against RSV disease, including severe disease, is likely maintained
Overall, the benefit: risk of coadministration of mRNA -1345 with standard and high -dose influenza
vaccines, and COVID -19 vaccine is positive
Thank you
© 2024 Moderna, inc. All rights reserved.19•Investigators
•Study site personnel
•Laboratory personnel
•Most importantly, the individuals who participated in these trials19

Summary: © 2024 Moderna, inc. All rights reserved.RSV Vaccine ( mRESVIA , mRNA -1345)  Concomitant Administration Overview Advisory Committee on Immunization Practices Rituparna Das, MD PhD  Oct 24, 2024 1 © 2024 Moderna, inc. All rights reserved. Cumulative Burden of Seasonal Respiratory Viruses in US Older Adults RSV Influenza2 Cumulative US  Hospitalization Rate  (≥65 yr, rate/100,000, 9/28/2024)1 227 106 US Vaccine Coverage  2023 -242-4 (COVID -19 & Flu ≥65 yrs, RSV ≥60 yrs)70% 23% 1.CDC RESP -NET,…