03 Mening Crowe 508

National Center for Immunization & Respiratory Diseases
Evidence to Recommendations Framework:
Pfizer’s MenABCWY Vaccine
Sam Crowe, PhD, MPH
Meningococcal Vaccines Work Group Lead
June 23, 2023

Outline
▪Overview of policy questions and PICOs
▪Evidence to Recommendations framework
▪Summary of findings
▪WG proposed options
2
Pfizer MenABCWY Vaccine
▪Comprised of Trumenba (serogroup B) and Nimenrix (serogroups ACWY)
–Trumenba
•Consists of two purified recombinant lipidated FHbp antigens, one from each FHbp subfamily (A
and B)
•Currently licensed and available in US (10 –25 years)
–Nimenrix
•Meningococcal group A, C, W, and Y polysaccharide tetanus toxoid conjugate vaccine
•Not licensed in US but used extensively in Europe and elsewhere for over a decade
▪Clinical trial data
–Assessed
•Two doses (0,6 m and 0,12 m apart)
–Studied 10 through 25 years of age
–Both MenACWY primed and naïve subjects
–Longer interval studies underway (not available in time for initial product licensure)
3
Policy Questions for 3 PICOs
▪Should the pentavalent vaccine be included as an option for
MenACWY/MenB vaccination in people currently recommended to receive
both vaccines ? (PICO 1)
▪Should the pentavalent vaccine be included as an option for people
currently recommended to receive MenACWY only ? (PICO 2)
▪Should the pentavalent vaccine be included as an option for people
currently recommended to receive MenB only ? (PICO 3)
4
GRADE Table 1: Combined Policy Question and PICO
Policy 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 or older 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 ( as appropriate by PICO )
•Short -term immunity
•Persistent immunity
•Interference with other recommended vaccines administered concurrently
•Serious adverse events
•Non -serious adverse events
5
Routine Schedule and Increased Risk Populations
▪Routine schedule
–One MenACWY dose at 11 –12 years and a booster at 16 years
–Two MenB doses at 16 –18 years (shared clinical decision -making recommendation)
▪Increased risk, MenACWY (vaccines are interchangeable)
–Recommended for certain medical conditions
•Asplenia, complement deficiency, complement inhibitor use, and HIV infection
–Some microbiologists
–Exposure during an outbreak
–Travel to hyperendemic areas
–First -year college students
–Military recruits
▪Increased risk, MenB (vaccines are notinterchangeable)
–Recommended for certain medical conditions
•Asplenia, complement deficiency, and complement inhibitor use
–Some microbiologists
–Exposure during an outbreak 6
How PICOs Translate into Schedule Options for
Healthy Adolescents
Legend
Q = MenACWY (quadrivalent)
B = MenB
P = MenABCWY (pentavalent) 7Options11–12 year
old dose16 year old
dose #116 year old
dose #2
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
Public Health Problem
Is meningococcal disease a problem of public health importance?
9Meningococcal Disease Incidence —
United States, 1996 –2022*
0.000.200.400.600.801.001.201.40
1996 2000 2005 2010 2015 2020 2022Incidence per 100,000
Year
Source : 1996 –2022 NNDSS Data. *2021 –2022 NNDSS data are preliminary.0.09 cases/100,000
populationMenACWY vaccine1.2 cases/100,000
population
MenB vaccine
10Average Annual Meningococcal Disease Incidence by
Age Group and Serogroup ― United States, 2010 –2022*
Source: NNDSS data with additional serogroup data from the Active Bacterial Core Surveillance System and state health departm ents
*2022 data are preliminary00.20.40.60.811.2
<1 year 1 year 2-4
years5-10
years11-15
years16-20
years21-25
years26-44
years45-64
years65-84
years85+
yearsIncidence per 100,000
Age GroupB ACWY Oth/Unk
Even with treatment, morbidity and mortality are high
~10–15%
of cases are fatal
11
10–20% of survivors
have permanent sequelaeEven with treatment, mortality and morbidity are high
~10–15%
of cases are fatal
12
Summary of the Public Health Problem
▪Incidence of meningococcal disease
–Low
–Decreasing for some time
▪Causes very severe disease
▪Poor outcomes even with treatment
13
Public Health Problem —Work Group Interpretation
▪Is meningococcal disease a problem of public health importance?
No Probably No Probably Yes Yes Varies Don’t Know
14
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?
GRADE Appendix 1: Studies Included in Review of Evidence
Author, Year Study Design Country AgeNumber of
Participants Number
InterventionNumber
ComparisonData Sources
Pfizer (NCT04440163),
2020RCTUS, Czech R., Denmark,
Hungary, Poland10–25
years2412 1763 649Clinicaltrials.gov,
Pfizer WG and
ACIP
presentations,
Pfizer
correspondence,
Pfizer preliminary
results
presentations Pfizer (NCT03135834),
2017RCTUS, Czech R., Finland,
Poland10–25
years1600 543 1057
Pfizer (NCT04440176),
2020RCT US11–14
years294 294 N/A
16
GRADE Table 2: Outcomes and Rankings
Outcome Importance Included in Profile
Meningococcal disease caused by
serogroups A, B, C, W, and YCritical No
Short -term immunity Critical Yes
Persistent immunity Important Yes
Interference with other recommended
vaccines administered concurrentlyImportant No
Serious adverse events Critical Yes
Non -serious adverse events Important Yes
17
Complexity of Review
▪Four outcomes of interest in evidence profile
–Short -term immunity
–Persistent immunity
–Serious adverse events
–Non -serious adverse events
▪Three PICO questions
–PICO 1: MenABCWY as an option for MenACWY+MenB
–PICO 2: MenABCWY as an option for MenACWY
–PICO 3: MenABCWY as an option for MenB
▪Two populations
–Healthy individuals 10 years old or older
–People with medical conditions that put them at increased risk for invasive disease aged
10 years old or older (i.e., asplenia, complement deficiency, and HIV infection)
18
GRADE Table 4: Short -Term Immunity for Healthy Persons —PICOs 1, 2, and 3
19Certainty assessment № of patients Effect
Certainty Importance
№ of studies Study design Risk of bias Inconsistency Indirectness ImprecisionOther
considerationsPfizer
MenABCWYMenACWY
and MenBRelative
(95% CI)Absolute
(95% CI)
Short -term immunity for MenACWY (follow -up: 1 month)
1 randomized
trialsnot serious not serious serious1not serious none In naïve participants, short -term immunity increases slightly for
serogroups A, C, W, and Y at 1 month after 1 dose of
MenABCWY versus 1 dose of MenACWY -CRM:
Serogroup A (n=753), RR of 1.02 (95% CI: 0.99 –1.05)
Serogroup C (n=753), RR: 1.20 (95% CI: 1.05 –1.38)
Serogroup W (n=736), RR 1.09 (95% CI: 0.99 –1.19)
Serogroup Y (n=742), RR 1.16 (95% CI: 1.06 –1.27)
In primed participants, little or no difference was observed in
short -term immunity for serogroups A, C, W, and Y at 1 month
after 1 dose of MenABCWY versus 1 dose of MenACWY -CRM:
Serogroup A (n=666), RR of 0.98 (95% CI: 0.95 –1.01)
Serogroup C (n=665), RR: 0.99 (95% CI: 0.95 –1.03)
Serogroup W (n=650), RR 1.01 (95% CI: 0.98 –1.04)
Serogroup Y (n=665), RR 1.01 (95% CI: 0.97 –1.05) ⨁⨁⨁◯
ModerateCRITICAL
Short -term immunity for MenB (follow -up: 1 month)
1 randomized
trialsnot serious not serious serious1not serious none 591/755
(78.3%)2263/419
(62.8%)2RR 1.25
(1.15 to 1.36)15,692 more
per 100,000
(from 9,415
more to
22,597 more)⨁⨁⨁◯
ModerateCRITICAL
1hSBA titers are the established correlate of protection for serogroup C meningococcal disease. This correlation is assumed to exte ndto 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.
2Calculated based on serogroup B composite data.
GRADE Table 4: Short -Term Immunity for Persons at Increased Risk —PICOs 1, 2, and 3
20Certainty assessment № of patients Effect
Certainty Importance
№ of studies Study design Risk of bias Inconsistency Indirectness ImprecisionOther
considerationsPfizer
MenABCWYMenACWY
and MenBRelative
(95% CI)Absolute
(95% CI)
Short -term immunity for MenACWY (follow -up: 1 month)
1 randomized
trialsnot serious not serious very
serious1,2not serious none In naïve participants, short -term immunity increases slightly for
serogroups A, C, W, and Y at 1 month after 1 dose of
MenABCWY versus 1 dose of MenACWY -CRM:
Serogroup A (n=753), RR of 1.02 (95% CI: 0.99 –1.05)
Serogroup C (n=753), RR: 1.20 (95% CI: 1.05 –1.38)
Serogroup W (n=736), RR 1.09 (95% CI: 0.99 –1.19)
Serogroup Y (n=742), RR 1.16 (95% CI: 1.06 –1.27)
In primed participants, little or no difference was observed in
short -term immunity for serogroups A, C, W, and Y at 1 month
after 1 dose of MenABCWY versus 1 dose of MenACWY -CRM:
Serogroup A (n=666), RR of 0.98 (95% CI: 0.95 –1.01)
Serogroup C (n=665), RR: 0.99 (95% CI: 0.95 –1.03)
Serogroup W (n=650), RR 1.01 (95% CI: 0.98 –1.04)
Serogroup Y (n=665), RR 1.01 (95% CI: 0.97 –1.05) ⨁⨁◯◯
LowCRITICAL
Short -term immunity for MenB (follow -up: 1 month)
1 randomized
trialsnot serious not serious very
serious1,2not serious none 591/755
(78.3%)3263/419
(62.8%)3RR 1.25
(1.15 to 1.36)15,692 more
per 100,000
(from 9,415
more to
22,597 more)⨁⨁◯◯
LowCRITICAL
1Clinical trials did not include patients at increased risk for invasive disease.
2hSBA titers are the established correlate of protection for serogroup C meningococcal disease. This correlation is assumed to exte ndto 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.
3Calculated based on serogroup B composite data.
GRADE Table 4: Persistent Immunity for Healthy Persons —PICOs 1, 2, and 3
21Certainty assessment № of patients Effect
Certainty Importance№ of studies Study design Risk of bias Inconsistency Indirectness ImprecisionOther
considerationsPfizer
MenABCWYMenACWY
and MenBRelative
(95% CI)Absolute
(95% CI)
Persistent immunity for MenACWY (follow -up: 48 months)
1 randomized
trialsnot serious not serious very
serious1,2not serious none In naïve participants, seroprotection probably increases for
serogroups A, C, W, and Y at 48 months after 2 doses of
MenABCWY versus 54 months after 1 dose of MenACWY -CRM:
Serogroup A (n=112), RR of 1.29 (95% CI: 1.00 –1.67)
Serogroup C (n=113), RR: 1.63 (95% CI: 1.06 –2.49)
Serogroup W (n=111), RR 1.29 (95% CI: 1.05 –1.59)
Serogroup Y (n=113), RR 1.05 (95% CI: 0.98 –1.12)
In primed participants, little or no difference was observed in
seroprotection for serogroups A, C, W, and Y at 48 months after
2 doses of MenABCWY versus 54 months after 1 dose of
MenACWY -CRM:
Serogroup A (n=63), RR of 1.00 (95% CI: 1.00 –1.00)
Serogroup C (n=134), RR: 1.10 (95% CI: 1.01 –1.21)
Serogroup W (n=63), RR 1.10 (95% CI: 0.97 –1.24)
Serogroup Y (n=62), RR 1.00 (95% CI: 1.00 –1.00)⨁⨁◯◯
LowIMPORTANT
Persistent immunity for MenB (follow -up: 48 months)
1 randomized
trialsnot serious not serious serious2not serious none In naïve participants, little or no difference was observed in
seroprotection for serogroup B at 48 months after 2 doses of
MenABCWY versus 48 months after 2 doses of MenB -FHbp :
Serogroup B (A22) (n=233), RR of 0.88 (95% CI: 0.59 –1.31)
Serogroup B (A56) (n=243), RR: 1.17 (95% CI: 0.80 –1.70)
Serogroup B (B24) (n=243), RR 1.38 (95% CI: 0.93 –2.04)
Serogroup B (B44) (n=247), RR 1.13 (95% CI: 0.64 –1.98)⨁⨁⨁◯
ModerateIMPORTANT
1Comparisons were between 2 doses of MenABCWY and 1 dose of MenACWY -CRM. Comparisons also were staggered by 6 months.
2hSBA titers are the established correlate of protection for serogroup C meningococcal disease. This correlation is assumed to exte ndto 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.
GRADE Table 4: Persistent Immunity for Persons at Increased Risk —PICOs 1, 2, and 3
22Certainty assessment № of patients Effect
Certainty Importance№ of studies Study design Risk of bias Inconsistency Indirectness ImprecisionOther
considerationsPfizer
MenABCWYMenACWY
and MenBRelative
(95% CI)Absolute
(95% CI)
Persistent immunity for MenACWY (follow -up: 48 months)
1 randomized
trialsnot serious not serious very serious1,2,3 not serious none In naïve participants, seroprotection probably increases for
serogroups A, C, W, and Y at 48 months after 2 doses of
MenABCWY versus 54 months after 1 dose of MenACWY -CRM:
Serogroup A (n=112), RR of 1.29 (95% CI: 1.00 –1.67)
Serogroup C (n=113), RR: 1.63 (95% CI: 1.06 –2.49)
Serogroup W (n=111), RR 1.29 (95% CI: 1.05 –1.59)
Serogroup Y (n=113), RR 1.05 (95% CI: 0.98 –1.12)
In primed participants, little or no difference was observed in
seroprotection for serogroups A, C, W, and Y at 48 months after
2 doses of MenABCWY versus 54 months after 1 dose of
MenACWY -CRM:
Serogroup A (n=63), RR of 1.00 (95% CI: 1.00 –1.00)
Serogroup C (n=134), RR: 1.10 (95% CI: 1.01 –1.21)
Serogroup W (n=63), RR 1.10 (95% CI: 0.97 –1.24)
Serogroup Y (n=62), RR 1.00 (95% CI: 1.00 –1.00)⨁⨁◯◯
LowIMPORTANT
Persistent immunity for MenB (follow -up: 48 months)
1 randomized
trialsnot serious not serious very serious2,3 not serious none In naïve participants, little or no difference was observed in
seroprotection for serogroup B at 48 months after 2 doses of
MenABCWY versus 48 months after 2 doses of MenB -FHbp :
Serogroup B (A22) (n=233), RR of 0.88 (95% CI: 0.59 –1.31)
Serogroup B (A56) (n=243), RR: 1.17 (95% CI: 0.80 –1.70)
Serogroup B (B24) (n=243), RR 1.38 (95% CI: 0.93 –2.04)
Serogroup B (B44) (n=247), RR 1.13 (95% CI: 0.64 –1.98)⨁⨁◯◯
LowIMPORTANT
1Comparisons were between 2 doses of MenABCWY and 1 dose of MenACWY -CRM. Comparisons also were staggered by 6 months.
2Clinical trials did not include patients at increased risk for invasive disease.
3hSBA titers are the established correlate of protection for serogroup C meningococcal disease. This correlation is assumed to exte ndto 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.
GRADE Table 4: Serious Adverse Events for Healthy and Increased Risk —PICOs 1,
2, and 3
231 Comparisons were between 2 doses of MenABCWY and 1 dose of MenACWY -CRM plus 2 doses of MenB -FHbp .
2Downgraded because relative effect confidence intervals are wide.
3Clinical trials did not include patients at increased risk for invasive disease. Certainty assessment № of patients Effect
Certainty Importance
№ of studies Study design Risk of bias Inconsistency Indirectness ImprecisionOther
considerationsPfizer
MenABCWYMenACWY
and MenBRelative
(95% CI)Absolute
(95% CI)
2 randomized
trialsnot serious not serious serious1serious2none 13/2306
(0.6%) 8/1706 (0.5%) RR 1.94
(0.72 to 5.22)441 more per
100,000
(from 131
fewer to 1979
more)⨁⨁◯◯
LowCRITICALHealthy Persons
Persons at Increased Risk
Certainty assessment № of patients Effect
Certainty Importance
№ of studies Study design Risk of bias Inconsistency Indirectness ImprecisionOther
considerationsPfizer
MenABCWYMenACWY
and MenBRelative
(95% CI)Absolute
(95% CI)
2 randomized
trialsnot serious not serious very
serious1,3Serious2none 13/2306
(0.6%) 8/1706 (0.5%) RR 1.94
(0.72 to 5.22)441 more per
100,000
(from 131
fewer to 1979
more)⨁◯◯◯
Very lowCRITICAL
GRADE Table 4: Non -Serious Adverse Events Healthy and Increased Risk —PICOs
1, 2, and 3
Healthy Persons
Persons at Increased Risk
241Comparisons were between 2 doses of MenABCWY and 1 dose of MenACWY -CRM plus 2 doses of MenB -FHbp .
2Downgraded because absolute effect confidence intervals are wide.
3Clinical trials did not include patients at increased risk for invasive disease. Certainty assessment № of patients Effect
Certainty Importance№ of studies Study design Risk of bias Inconsistency Indirectness ImprecisionOther
considerationsPfizer
MenABCWYMenACWY
and MenBRelative
(95% CI)Absolute
(95% CI)
Non -serious adverse events (assessed with: All adverse events through 1 month after 2nd vaccination)
2 randomized
trialsnot serious not serious serious1serious2none 581/2306
(25.2%) 387/1706
(22.7%) RR 1.31
(1.17 to 1.47)7,032 more
per 100,000
(from 3,856
more to
10,662 more)⨁⨁◯◯
LowIMPORTANT
Certainty assessment № of patients Effect
Certainty Importance№ of studies Study design Risk of bias Inconsistency Indirectness ImprecisionOther
considerationsPfizer
MenABCWYMenACWY
and MenBRelative
(95% CI)Absolute
(95% CI)
Non -serious adverse events (assessed with: All adverse events through 1 month after 2nd vaccination)
2 randomized
trialsnot serious not serious Serious1,3serious2none 581/2306
(25.2%) 387/1706
(22.7%) RR 1.31
(1.17 to 1.47)7,032 more
per 100,000
(from 3,856
more to
10,662 more)⨁◯◯◯
Very lowIMPORTANT
25Benefits and Harms —Work Group Interpretation
▪How substantial are the desirable anticipated effects?
Minimal Small Moderate Large Varies Don’t KnowPICO 1 (MenABCWY as an option for MenACWY+MenB)
PICO 3 (MenABCWY as an option for MenB)PICO 2 (MenABCWY as an option for MenACWY)
Minimal Small Moderate Large Varies Don’t Know
Minimal Small Moderate Large Varies Don’t Know
26Benefits and Harms —Work Group Interpretation
▪How substantial are the undesirable anticipated effects?
Minimal Small Moderate Large Varies Don’t KnowPICO 1 (MenABCWY as an option for MenACWY+MenB)
PICO 3 ( MenABCWY as an option for MenB )PICO 2 ( MenABCWY as an option for MenACWY )
Minimal Small Moderate Large Varies Don’t Know
Minimal Small Moderate Large Varies Don’t Know
27Benefits and Harms —Work Group Interpretation
▪Do the desirable effects outweigh the undesirable effects?
Favors
interventionFavors
comparisonFavors both Favors neither Varies Don’t KnowPICO 1 ( MenABCWY as an option for MenACWY+MenB )
PICO 3 ( MenABCWY as an option for MenB )PICO 2 ( MenABCWY as an option for MenACWY )
Favors
interventionFavors
comparisonFavors both Favors neither Varies Don’t Know
Favors
interventionFavors
comparisonFavors both Favors neither Varies Don’t Know
Values
-Does the target population feel that the desirable effects are large relative to
undesirable effects?
-Is there important uncertainty about or variability in how much people value
the main outcomes?
Perspective of the Target Population
▪Limited data are available on values of the target population toward
inclusion of the pentavalent vaccine
▪In 2021, vaccination coverage of at least 1 dose was 89% for MenACWY
and 31% for MenB among adolescents
▪Limited data are available on vaccine uptake in other individuals
recommended to receive MenACWY or MenB vaccine
29
Reduced Doses
▪“Use of combination vaccines can reduce the number of injections patients receive
and alleviate concern associated with the number of injections… The use of a
combination vaccine generally is preferred over separate injections of the
equivalent component vaccines. Considerations should include provider
assessment, patient preference, and the potential for adverse events.”1
▪“Combination vaccines represent one solution to the issue of increased numbers
of injections during single clinic visits and generally are preferred over separate
injections of equivalent component vaccines.”2
1 General Best Practice Guidelines for Immunization. Best Practice Guidance of the ACIP. https://www.cdc.gov/vaccines/hcp/acip -recs/general -
recs/downloads/general -recs.pdf
2 American Academy of Pediatrics. Red Book 2018. Report of the Committee on Infectious Diseases. 31stEd. https://seciss.facmed.unam.mx/wp -
content/uploads/2021/02/Red -Book -31th -Edition.pdf 30
Values —Work Group Interpretation
▪Does the target population feel that the desirable effects are large relative to undesirable effects?
No Probably No Probably Yes Yes Varies Don’t KnowPICO 1 ( MenABCWY as an option for MenACWY+MenB )
PICO 3 ( MenABCWY as an option for MenB )PICO 2 ( MenABCWY as an option for MenACWY )
No Probably No Probably Yes Yes Varies Don’t Know
No Probably No Probably Yes Yes Varies Don’t Know
31
Uncertainty in How People Value the Outcomes
▪Limited data available on how much people value the main outcomes
▪Vaccination rates for MenACWY , a routine recommendation, are high
among the target population
▪Vaccination rates for MenB are considerably lower, but decisions to
vaccinate are based on shared clinical decision -making
–Cause for lower rates unclear: lack of interest in vaccination, lack of awareness
of option?
32
Values —Work Group Interpretation
▪Is there important uncertainty about or variability in how much people value the main outcomes?
Important
uncertainty or
variabilityProbably important
uncertainty or
variabilityProbably not
important
uncertainty or
variabilityNo important
uncertainty or
variabilityNo known
undesirable
outcomesPICO 1 ( MenABCWY as an option for MenACWY+MenB )
PICO 3 ( MenABCWY as an option for MenB )PICO 2 ( MenABCWY as an option for MenACWY )
Important
uncertainty or
variabilityProbably important
uncertainty or
variabilityProbably not
important
uncertainty or
variabilityNo important
uncertainty or
variabilityNo known
undesirable
outcomes
Important
uncertainty or
variabilityProbably important
uncertainty or
variabilityProbably not
important
uncertainty or
variabilityNo important
uncertainty or
variabilityNo known
undesirable
outcomes
33
Acceptability
-Is the intervention acceptable to key stakeholders?
35Stakeholder Acceptability
▪Limited data are available on the acceptance among key stakeholders of including MenABCWY
as an option in the current vaccination schedule
▪Proponents for increasing MenB vaccination likely would be supportive
–Pentavalent vaccine combines MenB (a shared clinical decision -making recommendation)
with MenACWY (a standard recommendation)
–Could increase vaccination rates against serogroup B
▪Patients who seek vaccination against all 5 serogroups also might be supportive due to the
reduced number of doses needed (4 versus 3)
▪Health care providers might be supportive, particularly if they could stock fewer vaccines1,2
1CDC. Timing and Spacing of Immunobiologics : General Best Practice Guidelines for Immunization. ACIP Timing and Spacing Guidelines
for Immunization | CDC .
2Hall E, Odafe S, Madden J, Schillie S. Qualitative Conceptual Content Analysis of COVID -19 Vaccine Administration Error Inquiries.
Vaccines . 2023; 11(2):254.
36Acceptability —Work Group Interpretation
▪Is the intervention acceptable to key stakeholders?
No Probably Probably Yes Yes Varies Don’t KnowPICO 1 (MenABCWY as an option for MenACWY+MenB)
PICO 3 (MenABCWY as an option for MenB)PICO 2 (MenABCWY as an option for MenACWY)
No Probably No Probably Yes Yes Varies Don’t Know
No Probably No Probably Yes Yes Varies Don’t Know
Resource Use
-Is the intervention a reasonable and efficient allocation of resources?
38CDC Cost Effectiveness Model Summary
▪Weighted cost per dose + administration
–MenACWY: $163 ($128 –$191)
–MenB: $210 ($155 –$250)
–MenABCWY: $278 ($255 –$290)
•Most MenABCWY strategies would save more or the same number of cases as the
standard of care, but they would do so at a much higher cost perQALY saved
•The exception is the Q -P-B, which could be incrementally cost saving (ICER QALY <0)
relative to the standard of care
39Resource Use —Work Group Interpretation
▪Is the intervention a reasonable and efficient allocation of resources?
No Probably No Probably Yes Yes Varies Don’t KnowPICO 1 (MenABCWY as an option for MenACWY+MenB)
PICO 3 (MenABCWY as an option for MenB)PICO 2 (MenABCWY as an option for MenACWY)
No Probably No Probably Yes Yes Varies Don’t Know
No Probably No Probably Yes Yes Varies Don’t Know
Equity
-What would be the impact on health equity?
41Equity Considerations
▪Limited data are available on the impact of the pentavalent vaccine on health
equity
▪It is not expected that the vaccine will negatively impact equity
▪It could potentially reduce disparities among those who might be interested in
being vaccinated against serogroup B but who might not receive clinical care that
includes discussion of the MenB vaccine
42Equity —Work Group Interpretation
▪What would be the impact on health equity?
ReducedProbably
ReducedProbably No
ImpactProbably
IncreasedIncreased Varies Don’t KnowPICO 1 (MenABCWY as an option for MenACWY+MenB)
PICO 3 (MenABCWY as an option for MenB)PICO 2 (MenABCWY as an option for MenACWY)
ReducedProbably
ReducedProbably No
ImpactProbably
IncreasedIncreased Varies Don’t KnowReducedProbably
ReducedProbably No
ImpactProbably
IncreasedIncreased Varies Don’t Know
Feasibility
-Is the intervention feasible to implement?
44Feasibility Considerations
▪Challenges with insurance coverage specific to the pentavalent vaccine not expected
▪Substantial financial burdens for providers or health systems not expected
▪Pentavalent vaccine likely would be easily integrated into providers' practices
–Would provide additional option in current schedule
–Administration of the pentavalent vaccine is of equal complexity as currently available vaccines
–Barriers to stocking the pentavalent vaccine not expected
–Unclear, however, whether providers are willing to stock three different vaccine types
▪Providers who routinely vaccinate persons aged 16 –18 years might have an incentive to stock the
vaccine to reduce the number of doses given to patients who prefer vaccination against all 5
serogroups
45Feasibility —Work Group Interpretation
▪Is the intervention feasible to implement?
No Probably No Probably Yes Yes Varies Don’t KnowPICO 1 (MenABCWY as an option for MenACWY+MenB)
PICO 3 (MenABCWY as an option for MenB)PICO 2 (MenABCWY as an option for MenACWY)
No Probably No Probably Yes Yes Varies Don’t Know
No Probably No Probably Yes Yes Varies Don’t Know
Summary
47EtR Summary for PICO 1 (MenABCWY as an option for MenACWY+MenB)
Domain Question Work Group Judgment
Public health problem Is meningococcal disease a public health problem? Yes
Benefits and harmsHow substantial are the desirable anticipated effects? Small
How substantial are the undesirable anticipated effects? Small
Do the desirable effects outweigh the undesirable effects? Favors intervention
What is the overall certainty of the evidence profile? Varies by group
ValuesDoes the target population feel the desirable effects are large relative to
the undesirable effects? Probably yes
Is there important uncertainty about or variability in how much people
value the main outcomes? Probably not important
uncertainty or variability
Acceptability Is the intervention acceptable to key stakeholders? Probably yes or yes
Resource use Is the intervention a reasonable and efficient allocation of resources? Probably yes or yes
Equity What would be the impact on health equity? Probably no impact or
varies
Feasibility Is the intervention feasible to implement? Probably yes or yes
48Balance of Consequences —PICO 1 (MenABCWY as an option for
MenACWY+MenB)
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 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
Is there sufficient information to move forward with a recommendation?
Yes No
49EtR Summary for PICO 2 (MenABCWY as an option for MenACWY)
Domain Question Work Group Judgment
Public health problem Is meningococcal disease a public health problem? Yes
Benefits and harmsHow substantial are the desirable anticipated effects? Minimal, small, or
moderate
How substantial are the undesirable anticipated effects? Minimal or small
Do the desirable effects outweigh the undesirable effects? Favors intervention,
comparison, or both
What is the overall certainty of the evidence profile? Varies by group
ValuesDoes the target population feel the desirable effects are large relative to
the undesirable effects? Probably yes
Is there important uncertainty about or variability in how much people
value the main outcomes? Probably important
uncertainty or variability
Acceptability Is the intervention acceptable to key stakeholders? Probably yes or yes
Resource use Is the intervention a reasonable and efficient allocation of resources? Probably no or no
Equity What would be the impact on health equity? Probably increased, varies,
or don’t know
Feasibility Is the intervention feasible to implement? Probably yes or yes
50Balance of Consequences —PICO 2 (MenABCWY as an option for
MenACWY)
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
Is there sufficient information to move forward with a recommendation?
Yes No
51EtR Summary for PICO 3 (MenABCWY as an option for MenB)
Domain Question Work Group Judgment
Public health problem Is meningococcal disease a public health problem? Yes
Benefits and harmsHow substantial are the desirable anticipated effects? Minimal
How substantial are the undesirable anticipated effects? Minimal to small
Do the desirable effects outweigh the undesirable effects? Favors intervention or
comparison
What is the overall certainty of the evidence profile? Varies by group
ValuesDoes the target population feel the desirable effects are large relative to
the undesirable effects? Probably yes or don’t know
Is there important uncertainty about or variability in how much people
value the main outcomes? Important or probably
important
Acceptability Is the intervention acceptable to key stakeholders? Don’t know
Resource use Is the intervention a reasonable and efficient allocation of resources? Probably yes or yes
Equity What would be the impact on health equity? Don’t know
Feasibility Is the intervention feasible to implement? Probably yes or yes
52Balance of Consequences —PICO 3 (MenABCWY as an option for MenB)
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 settings Desirable
consequences
clearly outweigh
undesirable
consequences in
most settings There is
insufficient
evidence to
determine the
balance of
consequences
Is there sufficient information to move forward with a recommendation?
Yes No
Proposed Options
54Work Group Interpretation, PICO 1
We do not recommend the intervention, but it may be used within FDA licensed indications
We recommend the intervention for individuals based on shared clinical decision -making
We recommend the intervention▪Should the pentavalent vaccine be included as an option for MenACWY/MenB
vaccination in people currently recommended to receive both vaccines ?
55Work Group Interpretation, PICO 2
We do not recommend the intervention, but it may be used within FDA licensed indications
We recommend the intervention for individuals based on shared clinical decision -making
We recommend the intervention▪Should the pentavalent vaccine be included as an option for people
currently recommended to receive MenACWY only ?
56Work Group Interpretation, PICO 3
We do not recommend the intervention, but it may be used within FDA licensed indications
We recommend the intervention for individuals based on shared clinical decision -making
We recommend the intervention▪Should the pentavalent vaccine be included as an option for people
currently recommended to receive MenB only ?
▪WG was divided on this option, but a small majority were in favor of not
proposing
▪WG agreed to have ACIP consider the strengths and weaknesses of this
option
Schedule Options
Legend
Q = MenACWY (quadrivalent)
B = MenB
P = MenABCWY (pentavalent) 57Options11–12 year
old dose16 year old
dose #116 year old
dose #2WG
Decision
Standard of care (MenACWY only) Q Q – N/A
Standard of care (MenACWY + MenB) Q Q+B B N/A
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

58Draft Proposal to the ACIP
▪Forindividuals aged 10 years or older, Pfizer’s MenABCWY vaccine may be used as an alternative to
MenACWY and MenB vaccines only when both vaccines are indicated to be given at the same time.
This proposal applies to healthy individuals (routine schedule) and those at increased risk for
meningococcal disease.
59Draft Proposal to the ACIP
▪Forindividuals aged 10 years or older, Pfizer’s MenABCWY vaccine may be used as an alternative to
MenACWY and MenB vaccines only when both vaccines are indicated to be given at the same time.
This proposal applies to healthy individuals (routine schedule) and those at increased risk for
meningococcal disease.
–Remarks:
•This proposal is not intended to supersede or negate the shared clinical decision -making
recommendation for MenB.
•The licensed MenB vaccines are not interchangeable, so use of the Pfizer pentavalent vaccine for
the first MenB dose would require subsequent doses to be a Pfizer MenB -FHbp vaccine or
pentavalent Pfizer MenB -FHbp -containing vaccine.
•The minimum interval for the Pfizer pentavalent vaccine is 6 months. Individuals at increased risk of
meningococcal disease who are recommended to receive additional doses of MenACWY and MenB
less than 6 months after a dose of pentavalent meningococcal vaccine should instead receive
separate MenACWY and MenB -FHbp vaccines.
•The workgroup will review extended interval data when available in anticipation that this may
provide support for updated schedules that provide protection for all 5 serogroups.
Strengths and Weaknesses of Q -P-B (PICO 1)
▪ Strengths
– Reduces doses from 4 to 3
– Cost savings
• ~$95 per person for the routine schedule
• Q-Q-B-B (~$746) vs. Q -P-B (~$651)
– CostperQALY saved less than standard of care
– Relatively straightforward proposal
▪ Weaknesses
– Does not match dosing used in clinical trials (2 doses at 0,6m)
– Would require stocking 3 vaccine types (MenACWY , MenABCWY , MenB), which might not be acceptable to some clinicians
– Some clinics might not have funds available to stock multiple formulations, which could increase inequities
– Could be challenging for some recipients to complete MenB series if provider does not carry MenB -FHbp
– If ACIP does not recommend second dose of MenABCWY , insurance companies might not cover it in lieu of MenB
– Potentially could increases risk of provider vaccine administration error1,2
601CDC. Timing and Spacing of Immunobiologics : General Best Practice Guidelines for Immunization. ACIP Timing and Spacing Guidelines for Immunization | CDC .
2Hall E, Odafe S, Madden J, Schillie S. Qualitative Conceptual Content Analysis of COVID -19 Vaccine Administration Error Inquiries. Vaccines . 2023; 11(2):254.
Strengths and Weaknesses of Q -P-P (PICO 3)
▪ Strengths
–Reduces doses from 4 to 3
–Small cost savings
•~$27 per person for the routine schedule
•Q-Q-B-B (~$746) vs. Q -P-P (~$719)
–Relatively straightforward proposal
–Potentially allows stocking two vaccines for most patients
–Matches dosing used in clinical trials (2 doses at 0,6m)
▪ Weaknesses
–Persons needing 3 doses of MenB would still need Trumenba because of 6m minimum interval
–Less cost savings than Q -P-B
–Higher cost perQALY saved compared to standard of care
–Concerns from WG that this option could lead to MenB vaccine being discontinued (but need for
Trumenba for persons at increased risk might reduce likelihood)
61
Comparison of Q -P-B and Q -P-P
Criteria Q-P-B Q-P-P
Number of doses saved 1 1
Cost savings per person compared to standard of care $95 $27
Less cost perQALY saved than standard of care Yes No
Number of vaccine types required for the routine schedule 3 2
Number of vaccines types required for the increased -risk schedule 3 3
Matches dosing used in clinical trials No Yes
Unnecessary doses of one or more serogroups No Yes
62
63Acknowledgments
▪ ACIP Members on the WG
–Kathy Poehling (Chair)
–Lynn Bahta
–Jamie Loehr
▪ Ex Officio WG Members
–Margaret Bash (FDA)
–Mark Connelly (FDA)
–Francisco Leyva (NIH)
▪ WG Liaisons and Consultants
–Amra Resic (AAFP)
–Samir Shah (AAP)
–Sharon McMullen (ACHA)
–Cacky Tate (AIM)
–Paul Cieslak (CSTE)
–Kathy Hsu (IDSA)
–Joseline Zafack (NACI)
–Jeff Goad (NFID)
–Jessica Cataldi (PIDS)
–Amy Middleman (SAHM)
–David Stephens (Emory)▪ CDC Contributors
–Jenn Collins (DBD/NCIRD)
–Lucy McNamara (DBD/NCIRD)
–LeAnne Fox (DBD/NCIRD)
–Susan Hariri (DBD/NCIRD)
–Amy Rubis (DBD/NCIRD)
–Noele Nelson (DBD/NCIRD)
–Alison Albert (DBD/NCIRD)
–Angela Jiles (DBD/NCIRD)
–Jonathan Duffy (DHQP/NCEZID)
–Tanya Myers (DHQP/NCEZID)
–Ismael Ortega -Sanchez (DVD/NCIRD)
–Liz Velazquez (ISD/NCIRD)
–Jessica MacNeil (ACIP Secretariat)
▪ GRADE/EtR Support
–Doug Campos -Outcalt (Arizona)
–Rebecca Morgan (Case Western Reserve)
Backup Slides
Evidence Retrieval
▪Systematic review of studies in any language from Medline, Embase,
Global Health, CINAHL, Cochrane, Scopus, and clinicaltrials.gov databases
using search string:
–meningococcal pentavalent, pentavalent meningococcal, Pfizer pentavalent meningococcal,
MenABCWY , Pfizer MenABCWY , pentavalent MenABCWY ,
ABCWY , MenABCWY meningococcal, Neisseria meningitidis group A, B, C, W, and Y , Neisseria
meningitidis A, B, C, W, and Y , Neisseria meningitidis pentavalent, bivalent RLP2086 -containing
pentavalent, NCT03135834, B1971057, NCT04440163, C3511001, NCT04440176, C3511004, and
“vaccin *”
▪Efforts made to obtain unpublished or other relevant data
▪Included results that presented primary data on Pfizer’s MenABCWY
vaccine
65
Evidence Screening Steps
Materials shared by
Pfizer (n=5)References identified
in database search
(n=43)
Title and abstract
screening (n=43)
Full-text article or
public data screening
(n=14)
Records excluded
(n=10)Records excluded
(n=29)
Data sources included
in GRADE analysis: 9
(documenting results
of 3 clinical trials)66
GRADE Certainty of Evidence Categories
Evidence
TypeStudy Design
HighRandomized controlled trials (RCTs) or overwhelming evidence
from observational studies
ModerateRCTs with important limitations, or exceptionally strong
evidence from observational studies
Low Observational studies, or RCTs with notable limitations
Very lowClinical experience and observations, observational studies with
important limitations, or RCTs with several major limitations
67
Short -Term Immunity Key Findings (Table 3a)
Author,
Pub yearAgeSerogroup
(Test strain)n/N
ABCWYn/N
comparisonIntervention
vaccineComparator
vaccine% (95% CI) for
intervention% (95% CI) for
comparator Effect estimate —
RR (95% CI)
Seroresponse based on hSBA titer11 month after 1 intervention dose
Pfizer CT
(NCT04440163),
202010–25 years;
ACWY naïveA 484/499 242/254
MenABCWY (1
dose)MenACWY -
CRM (1 dose)
+ MenB -
FHbp (1
dose) 97.0% (95.1 –98.3) 95.3% (91.9 –97.5) 1.02 (0.99 –1.05)
C 315/501 132/252 62.9% (58.5 –67.1) 52.4% (46.0 –58.7) 1.2 (1.05 –1.37)
W 390/492 178/244 79.3% (75.4 –82.8) 73.0% (66.9 –78.4) 1.09 (0.99 –1.19)
Y 405/494 175/248 82.0% (78.3 –85.3) 70.6% (64.5 –76.2) 1.16 (1.06 –1.27)
10–25 years;
ACWY primedA 416/439 220/227 94.8% (92.2 –96.7) 96.9% (93.7 –98.8) 0.98 (0.95 –1.01)
C 410/439 214/226 93.4% (90.7 –95.5) 94.7% (90.9 –97.2) 0.99 (0.95 –1.03)
W 417/428 214/222 97.4% (95.4 –98.7) 96.4% (93.0 –98.4) 1.01 (0.98 –1.04)
Y 417/442 209/223 94.3% (91.8 –96.3) 93.7% (89.7 –96.5) 1.01 (0.97 –1.05)
Seroresponse based on hSBA titer 1 month after 2 intervention doses
Pfizer CT
(NCT0444016
3), 202010–25 years;
B naïve2B (A22) 646/778 313/396
MenABCWY
(2 doses 6
months
apart)MenACW
Y-CRM (1
dose) +
MenB -
FHbp (2
doses 6
months
apart)83% (80.2 –85.6) 79.0% (74.7 –82.9) 1.05 (0.99 –1.12)
B (A56) 774/807 378/400 95.9% (94.3 –97.2) 94.5% (91.8 –96.5) 1.01 (0.99 –1.04)
B (B24) 567/833 239/418 68.1% (64.8 –71.2) 57.2% (52.3 –62.0) 1.19 (1.08 –1.31)
B (B44) 731/845 332/419 86.5% (84.0 –88.7) 79.2% (75.0 –83.0) 1.09 (1.03 –1.15)
B (composite) 591/755 263/419 78.3% (75.2 –81.2) 68.7% (63.8 –73.3) 1.25 (1.15 –1.35)
681hSBA = serum bactericidal assay using human complement. For participants with a baseline hSBA titer <1:4, seroresponse is defined as a titer ≥1:16. For those with a baseline hSBA titer ≥1:4 and
<1:8 (<1:16 for A22), seroresponse is a titer ≥4 times the 1:8 (1:16 for A22). For those with a baseline hSBA titer ≥1:8 (≥1:16 for A22), seroresponse is a titer ≥4 times the baseline titer.
2Serogroup B primed not assessed.
Persistent Immunity Key Findings (Table 3b)
Author, pub year AgeSerogroup
(Test strain)n/N
MenABCWYn/N
comparisonIntervention
vaccine Comparator
vaccine% (95% CI) for
intervention% (95% CI) for
comparator Effect estimate —
RR (95% CI)
Seroprotection (defined as hSBA titer ≥1:8 for all but A22 which is ≥1:16) at 48 months (54 months for MenACWY -CRM) after last dose
Pfizer CT
(NCT03135834)
201710–25 years;
ACWY naïveA 58/71 26/41
MenABCWY (2
doses 6 months
apart)MenACWY -
CRM (1 dose) +
MenB -FHbp (2
doses 6 months
apart) 81.7% (70.7 –89.9) 63.4% (46.9 –77.9) 1.29 (1.00 –1.67)
C 44/71 16/42 62.0% (49.7 –73.2) 38.1 % (23.6 –54.4) 1.63 (1.06 –2.49)
W 64/70 29/41 91.4% (82.3 –96.8) 70.7% (54.5 –83.9) 1.29 (1.05 –1.59)
Y 71/71 40/42 100.0% (94.9 –100.0) 95.2% (83.8 –99.4) 1.05 (0.98 –1.12)
10–25 years;
B naïveB (A22) 39/139 30/94 28.1% (20.8 –36.3) 31.9% (22.7 –42.3) 0.88 (0.59 –1.31)
B (A56) 50/145 29/98 34.5% (26.8 –42.8) 29.6% (20.8 –39.7) 1.17 (0.80 –1.70)
B (B24) 53/145 26/98 36.6% (28.7 –44.9) 26.5% (18.1 –36.4) 1.38 (0.93 –2.04)
B (B44) 27/148 16/99 18.2% (12.4 –25.4) 16.2% (9.5 –24.9) 1.13 (0.64 –1.98)
10–25 years;
ACWY
primedA 40/40 23/23 100.0% (91.2 –100.0) 100.0% (85.2 –100.0) 1.00 (1.00 –1.00)
C 75/76 52/58 98.7% (92.9 –100.0) 89.7% (78.8 –96.1) 1.10 (1.01 –1.21)
W 40/40 21/23 100.0% (91.2 –100.0) 91.3% (72.0 –98.9) 1.10 (0.97 –1.24)
Y 40/40 22/22 100.0% (91.2 –100.0) 100.0% (84.6 –100.0) 1.00 (1.00 –1.00)
Persistent Immunity Key Findings, Continued
Author, pub year Age Serogroupn/N
MenABCWYn/N
comparisonIntervention
vaccine Comparator
vaccine% (95% CI) for
intervention% (95% CI) for
comparator Effect estimate —RR (95% CI)
Seroprotection (defined as hSBA titer ≥1:8) at 13 months (12 months for MenACWY -CRM) after last dose
Pfizer CT
(NCT04440176),
2020, and Pfizer CT
(NCT03135834), 201711–14 years for
NCT04440176
and 10 –25 years
for
NCT03135834;
both groups
ACWY naiveA 102/126 42/59
1 dose of
MenABCWY1 dose of
MenACWY -CRM81.0% (73.0 –87.4) 71.2% (57.9 –82.2) 1.14 (0.95 –1.37)
C 92/127 32/62 72.4% (63.8 –80.0) 51.6% (38.6 –64.5) 1.40 (1.08 –1.83)
W 125/128 52/62 97.7% (93.3 –99.5) 83.9% (72.3 –92.0) 1.16 (1.04 –1.30)
Y 122/126 61/62 96.8% (92.1 –99.1)98.4% (91.3 –
100.0)0.98 (0.94 –1.03)
70
Serious Adverse Event Findings
1Nine SAEs occurred in 7 patients: Salmonella gastroenteritis (1 patient), depression (1 patient), anxiety (1 patient), suicide attempt (1 patient),
postural orthostatic tachycardia syndrome (1 patient), dyspnea (1 patient), head injury due to motor vehicle accident (1 pati ent), traumatic spinal
cord injury (1 patient), depression with suicidal ideation (1 patient). None of the SAEs were deemed related to the vaccine by the study
investigators.
2Eight SAEs occurred in 6 patients: cyst (1 patient), tendon injury (1 patient), dyskinesia (1 patient), migraine with aura (1 patient), aggression (1
patient), conversion disorder (1 patient), suicidal ideation (2 patients). None of the SAEs were deemed related to the vaccine by the study
investigators. 711
2
Non -Serious Adverse Event Findings
72▪Additional findings related to non -serious adverse events
– NCT04440163: Attention -deficit/hyperactivity disorder (ADHD) was reported by 6 participants in the MenABCWY group
as newly diagnosed chronic medical conditions (NDCMC). Five had an onset of ADHD -related symptoms that occurred
prior to study enrollment and the remaining participant had a history of one or more conditions prior to enrollment
that commonly co -occur with ADHD, including anxiety, depression, and substance use. Overall, none of the NDCMCs
reported were considered related to vaccine by the investigators.
– No other non-serious adverse events that we are aware of were disproportionately overrepresented in the
MenABCWY group from any of the trials.
Nimenrix Background
▪Nimenrix is not approved in the United States, but has been available in
other parts of the world for about a decade
▪The next few slides provide some background on the vaccine’s safety,
immunogenicity, and potential interference with other routinely
administered vaccines
73
Nimenrix Safety
▪First licensed in the European Union in April 2012
▪Currently licensed in more than 80 countries worldwide
▪More than 20 thousand people participated in Nimenrix clinical trials
▪Over a decade of post -marketing safety data available
–More than 30 million doses given worldwide
–Safety consistent between CTs and post -marketing experience
–Most common adverse events —fever, headache, injection site pain, nausea/vomiting,
fatigue
–Serious adverse events rare relative to doses given
–Safety also consistent with other licensed meningococcal vaccines
1Serra et al. Clinical trial and postmarketing safety experience with MenACWY -TT, a meningococcal group A, C, W, and Y tetanus c onjugate vaccine.
Vaccine . 2022; 40:7014 –7021. 74
Nimenrix Safety, Continued
▪One clinical trial on MenACWY -TT and asplenia1
–Phase III, non -randomized study
–1 to 17 year olds with impaired splenic activity with age -matched healthy
controls
▪Results
–Both study groups had high and comparable hSBA vaccine response rates
across serogroups
•First dose: 55.6 –77.1% vs. 60.6 –76.3%
•Second dose: 73.0 –100% vs. 73.0 –85.3%
–SAEs were comparable (4/43 vs. 1/43) and none were deemed vaccine related
•Cystitis due to Escherichia coli , pneumococcal bacteremia, salmonellosis, and sickle -
cell anemia with crisis
1Klein et al. Immunogenicity and safety of the quadrivalent meningococcal ACWY -tetanus toxoid conjugate vaccine (MenACWY -TT) in
splenectomized orhyposplenic children and adolescents: Results of a phase III, open, non -randomized study. Vaccine . 2018. 36;2356 –2363. 75
Nimenrix Persistence Compared to Menactra —5 Years After
Primary Vaccination in Young Adults Aged 11 –25 Years1
1 Pfizer. Nimenrix Product Label. ShowLabeling.aspx (pfizer.com) . 050100150200250
A C W YGMT
SerogroupNimenrix
Menactra
76
Nimenrix Persistence Compared to MenQuadfi —3 Years After
Primary Vaccination in Children Aged 4 –5 Years1
1 Sanofi Pasteur. Immunogenicity and Safety of an Investigational Quadrivalent Meningococcal Conjugate Vaccine Administered as a Booster Dose in Children
Vaccinated 3 Years Earlier as Toddlers. EU Clinical Trials Registry. https://www.clinicaltrialsregister.eu/ctr -search/trial/2017 -001993 -40/results . 020406080100120
A C W YGMT
SerogroupNimenrix
MenQuadfi
77
Overall Certainty of Evidence —PICO 1 (Table 5)
Outcome ImportanceIncluded in
Evidence ProfileCertainty for
Healthy
IndividualsCertainty for
Individuals at
Increased Risk
Meningococcal disease caused by
serogroups A, B, C, W, and YCritical No – –
Short -term immunity Critical Yes Moderate Low
Persistent immunity Important Yes Low Low
Interference with other recommended
vaccines administered concurrentlyImportant No – –
Serious adverse events Critical Yes Low Very low
Non -serious adverse events Important Yes Low Very low
78
Overall Certainty of Evidence —PICO 2 (Table 5)
Outcome ImportanceIncluded in
Evidence ProfileCertainty for
Healthy
IndividualsCertainty for
Individuals at
Increased Risk
Meningococcal disease caused by
serogroups A, B, C, W, and YCritical No – –
Short -term immunity Critical Yes Moderate Low
Persistent immunity Important Yes Low Low
Interference with other recommended
vaccines administered concurrentlyImportant No – –
Serious adverse events Critical Yes Low Very low
Non -serious adverse events Important Yes Low Very low
79
Overall Certainty of Evidence —PICO 3 (Table 5)
Outcome ImportanceIncluded in
Evidence ProfileCertainty for
Healthy
IndividualsCertainty for
Individuals at
Increased Risk
Meningococcal disease caused by
serogroups A, B, C, W, and YCritical No – –
Short -term immunity Critical Yes Moderate Low
Persistent immunity Important Yes Moderate Low
Interference with other recommended
vaccines administered concurrentlyImportant No – –
Serious adverse events Critical Yes Low Very low
Non -serious adverse events Important Yes Low Very low
80
Equity Considerations
HISPANIC NON -HISPANIC NON -HISPANIC NON -HISPANIC
WHITE ONLY BLACK ONLY OTHER +
MULTIPLE
RACE
% 1+ dose MenB 31.83 30.88 39.67 24.73Among 17yos in NIS -Teen 2021:
81
Equity Considerations, Continued
82
83Equity Considerations, Continued
▪Potential equity issues exist involving meningococcal vaccination more generally1
–“Among adolescents aged 17 years, coverage with ≥2 MenACWY doses was 11.8 percentage
points lower for those living in non -MSAs than for those in MSA principal cities. Disparities
between non -MSAs and MSA principal cities were statistically significant for adolescents living at
or above the poverty level, but not for those living below the poverty level.”
–“Hispanic or Latino (Hispanic) adolescents had lower coverage with ≥2 MenACWY doses (−10.8
percentage points).”
–“Adolescents who were uninsured had lower coverage with ≥1 MenACWY dose.”
1 Pingali et al. National Vaccination Coverage Among Adolescents Aged 13 –17 Years —National Immunization Survey -Teen, United States, 2021.
MMWR . 2022. 71; 1101 –1108.
84Demographic Information for NCT04440163

85Routine and Increased Risk Vaccine Schedules for ≥10 Years Old
▪Routine
–One MenACWY dose at 11 –12 years and a booster at 16 years
–Two MenB doses at 16 –18 years
▪Increased risk, MenACWY (vaccines are interchangeable)
–Recommended for certain medical conditions (asplenia, complement deficiency, complement inhibitor use, and HIV infection),
some microbiologists, exposure during an outbreak, travel to hyperendemic areas, first -year college students, and military
recruits
–2 doses ≥8 weeks apart for primary vaccination (only 1 dose for microbiologists, travelers, military) and single booster dose
every 5 years thereafter for as long as person remains at increased risk
–Only 1 dose during outbreaks if ≥5 years since MenACWY primary vaccination
–Only 1 dose for first year college students within 5 years before starting college
▪Increased risk, MenB (vaccines are not interchangeable)
–Recommended for certain medical conditions (asplenia, complement deficiency, and complement inhibitor use), some
microbiologists, and exposure during an outbreak
–Bexsero: 2 doses ≥1 month apart followed by single dose 1 year later and every 2 –3 years thereafter for as long as person
remains at increased risk
–Trumenba: 3 doses at 0, 1 –2, and 6 months followed by single dose 1 year later and every 2 –3 years thereafter for period of
increased risk
–Only 1 dose during outbreaks if ≥1 year after MenB primary series

Summary: National Center for Immunization & Respiratory Diseases Evidence to Recommendations Framework: Pfizer’s MenABCWY Vaccine Sam Crowe, PhD, MPH Meningococcal Vaccines Work Group Lead June 23, 2023  Outline ▪Overview of policy questions and PICOs ▪Evidence to Recommendations framework ▪Summary of findings ▪WG proposed options 2 Pfizer MenABCWY Vaccine ▪Comprised of Trumenba (serogroup B) and Nimenrix (serogroups ACWY) –Trumenba •Consists of two purified recombinant lipidated FHbp antigens, one…


01 VaxSafety Shimabukuro 508

National Center for Emerging and Zoonotic Infectious Diseases
Vaccine safety updates
Advisory Committee on Immunization Practices (ACIP) meeting
June 23, 2023
Tom T. Shimabukuro, MD, MPH, MBA
Director, Immunization Safety Office
Division of Healthcare Quality Promotion
Centers for Disease Control and Prevention (CDC)

Session topics
▪Background on the CDC Immunization Safety Office (ISO) and ISO
efforts to evaluate studying the safety of the childhood
immunization schedule (Dr. Tom Shimabukuro)
▪The childhood immunization schedule and safety: Studies in the
Vaccine Safety Datalink (Dr. Matthew Daley)
▪Preliminary evaluation of aluminum content in childhood vaccines
and risk of asthma in a Danish nationwide cohort (Dr. Anders Hviid)
▪Discussion
2
CDC Immunization Safety Office (ISO) mission
▪Monitor the safety of vaccines given to children and adults
ISO key activities
▪Monitor newly recommended vaccines and new recommendations for existing vaccines
▪Monitor CDC priority vaccines, including seasonal influenza and COVID -19 vaccines
▪Conduct planned safety studies
▪Support data needs of the Advisory Committee on Immunization Practices (ACIP)
▪Assess individual risk factors for adverse events, conduct clinical case reviews, and provide
clinical consultation to U.S. healthcare providers and health departments about vaccine safety
questions for individual patients
▪Respond to vaccine safety inquiries
▪Conduct vaccine safety communication and education
▪Coordinate with state health departments
▪Prepare for pandemic and emergency responses3
4
VSD CISA
5
▪The lack of conclusive evidence linking adverse events to
multiple immunizations or other “schedule” exposures
suggests that the recommended schedule is safe.
▪The risks to participants' health, the cost and time involved,
and the ethical challenges all make the conduct of an
[randomized controlled trial] RCT unsuitable for addressing
the research questions, at least until further work with
secondary data has been conducted.
▪Although each new vaccine is evaluated in the context of the
overall immunization schedule that existed at the time of
review of that vaccine, elements of the schedule are not
evaluated once it is adjusted to accommodate a new
vaccine. Thus, key elements of the entire schedule —the
number, frequency, timing, order, and age at administration
of vaccines —have not been systematically examined in
research studies.
▪The most feasible approach to studying the safety of the
childhood immunization schedule is through analyses of
data obtained by [the Vaccine Safety Datalink] VSD. Institute of Medicine. The Childhood Immunization Schedule and
Safety: Stakeholder Concerns, Scientific Evidence, and Future
Studies. Washington (DC): National Academies Press (US); 2013.2013
6Four objectives of White Paper
1.Define types of alternative immunization schedules
and patterns of undervaccination that could be
evaluated, focusing on the first 24 months of age
2.Identify plausible adverse event outcomes that could
be related to the childhood immunization schedule,
with an emphasis on long -term adverse events
3.Suggest methodological approaches that could be
used to assess the safety of the recommended
schedule as a whole
4.Propose next steps for studying the safety of the
childhood immunization schedule within the VSD
White Paper on Studying the Safety of the Childhood
Immunization Schedule. For the Vaccine Safety Datalink (cdc.gov)2014
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.
Photo credit: James Gathany
(https://wwwn.cdc.gov/phil/
Details.aspx?pid=8876 )

Summary: National Center for Emerging and Zoonotic Infectious Diseases Vaccine safety updates Advisory Committee on Immunization Practices (ACIP) meeting June 23, 2023 Tom T. Shimabukuro, MD, MPH, MBA Director, Immunization Safety Office Division of Healthcare Quality Promotion  Centers for Disease Control and Prevention (CDC)  Session topics ▪Background on the CDC Immunization Safety Office (ISO) and ISO  efforts to evaluate studying the safety of the childhood  immunization schedule (Dr. Tom…


02 VaxSafety Daley 508

The Childhood Immunization Schedule and
Safety: Studies in the Vaccine Safety Datalink
Matthew F. Daley MD
Advisory Committee on Immunization Practices, June 23, 2023
KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH
•No conflicts of interest to disclose
•The findings in this presentation are those of the speaker and do not
necessarily represent the official position of the Centers for Disease
Control and PreventionDisclaimers
Schedule and Safety 2
KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH
•2013 Institute of Medicine* (IOM) Report
•Feasibility work in Vaccine Safety Datalink (VSD)
•Three published VSD studies
oAntigens and non -targeted infections
oSchedule and type 1 diabetes (T1DM)
oAluminum and asthma
•Future investigations
•Schedule and safety: broader contextOutline
3 Schedule and Safety*Now referred to as The National Academies of Sciences, Engineering, and Medicine (NASEM)
KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH
•Subtitle: Stakeholder Concerns, Scientific Evidence, and Future Studies
•Existing evidence supported safety of schedule “as a whole”
•Evidence gaps: each new vaccine added to existing schedule; safety studies
usually of acute adverse events; long -term health outcomes less well studied
•Committee conclusions:
oRandomized clinical trials not suitable approach to address research questions about
schedule for ethical reasons
oObservational studies needed in existing surveillance systems (including in VSD)
oMethods for such studies complex; feasibility work needed
oDevelop metrics for exposure to schedule
oFocus on long -term outcomes: allergic, autoimmune, neurologicIOM: The Childhood Immunization Schedule and Safety
4 Schedule and SafetyRef: Institute of Medicine, National Academies Press, 2013. DOI: 10.17226/13563.
KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH
•VSD: collaboration between CDC and integrated healthcare
organizations, conducts vaccine safety surveillance and research
•White Paper objectives:
oExposure: define measures of vaccination schedule which could be
evaluated, with focus on first 24 months of life
oOutcomes: identify plausible adverse events, with emphasis on long -term
adverse events
oKey design considerations, analytic approaches
•Potential outcomes prioritized based on feasibility, public health
significance, and public concernWhite Paper on Studying Schedule in VSD:
Feasibility, Study Design, Outcomes
5 Schedule and SafetyRef: Glanz JM et al, Vaccine. 2016;34 Suppl 1:A1 -A29.
KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH
•High priority outcomes included: allergic disorders (e.g., asthma),
autoimmune disease (e.g.,T1DM), neurologic (e.g., epilepsy)
•Some public concerns may have limited biologic plausibility
•Attention to bias, unmeasured confounding
o
o
oMisclassification bias: survey parents of under -vaccinated children
Use negative control outcomes (example: injuries)
Control for differences in health care utilization
•Plan for a long and complex process; any initial positive associations
will need studies to refute or replicate initial findingsWhite Paper, Additional Conclusions
6 Schedule and SafetyRef: 1) Glanz JM et al, Vaccine. 2016;34 Suppl 1:A1 -A29. 2) Daley MF et al, Vaccine. 2017;35(15):1873 -1878. 3 ) Daley MF et al, Acad Pediatr . 2018;18:754 -762.
KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH
•Public concern: early childhood immunization “overloads” immune system
•Design: Matched case -control
•Exposures: cumulative vaccine antigen exposure, estimated by summing
number of antigens in each vaccine dose birth through age 23 months
•Outcomes:
oNon-vaccine -targeted infections in emergency department and inpatient settings
from 24 through 47 months of age
oManual medical record review validation of sample of outcomes
•Matching: age, sex, presence of chronic diseaseVSD Study: Antigens and Non -Targeted Infections
7 Schedule and SafetyRef: Glanz MF et al, JAMA. 2018;319(9):906 -913.
KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH
•Among children with versus without non -vaccine -targeted infections
from 24 through 47 months of age, matched odds ratio for cumulative
vaccine antigen exposure not significant:
oMatched odds ratio, 0.94; 95% CI, 0.84 to 1.07
•Secondary analyses: consistent with primary findings
•Conclusions:
oNo association between number of antigens young children receive through
vaccines and likelihood of ED or inpatient encounters for infections
oNo evidence schedule “overwhelms” immune systemResults: Antigens and Non -Targeted Infections
8 Schedule and SafetyRef: Glanz MF et al, JAMA. 2018;319(9):906 -913.
KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH
•Public concern: vaccine antigens and ingredients (including aluminum, used as
adjuvant) interfere with immune function, increase risk of autoimmune disease
•Design: retrospective cohort
•Exposures:
o
o
oCumulative vaccine antigen
Cumulative vaccine aluminum
Average days under -vaccinated
•Outcome: T1DM, identified using diagnosis codes
•Follow up: Mean length of follow up >5 years
•Analyses adjusted for sex, race and ethnicity, maternal age, birth weight,
gestational age, utilization (number of well -child visits)VSD Study: Schedule and Type 1 Diabetes
9 Schedule and SafetyRef: Glanz MF et al, Pediatrics. 2021;148(6):e2021051910.
KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH
•Main analyses, three different exposures:
oCumulative vaccine antigen non-significant : adjusted hazard ratio 0.98; 95% CI, 0.97 –1.00
oCumulative vaccine aluminum inversely associated : adjusted hazard ratio 0.77; 95% CI, 0.60 –0.99
oAverage days under -vaccinated non-significant : adjusted hazard ratio 1.01; 95% CI, 0.99 –1.02
•Sensitivity analyses, factoring in family history T1DM: similar to
primary results
•Conclusions:
oVaccine schedule not associated with increased risk of T1DM
oDecreased risk at higher vaccine aluminum exposure: modest effect size;
more study needed to refute or replicate this findingResults: Schedule and Type 1 Diabetes
10 Schedule and SafetyRef: Glanz MF et al, Pediatrics. 2021;148(6):e2021051910.
KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH
•Public concern: vaccine ingredients (specifically aluminum, used as adjuvant)
increase risk of allergic disorders including asthma
•Biologic plausibility: based on animal data, aluminum in vaccines could “skew”
toward T -helper cell 2 (Th2) response; Th2 cells play role in allergic asthma
•Design: retrospective cohort
•Exposure: cumulative vaccine aluminum received birth through 23 months of age
•Outcome: persistent asthma at 24 through 59 months of age
oOne inpatient or two outpatient diagnoses of asthma PLUS
oOne or more prescriptions for a long -term asthma control medication
•All analyses done separately for children with and without eczemaVSD Study: Aluminum and Asthma
11 Schedule and SafetyRef: 1) Baylor NW et al, Vaccine. 2002;20 Suppl 3:S18 -23. 2) Goullé JP et al, Med Mal Infect. 2020;50:16 -21. 3) Hogenesch H. Front Immunol. 2012;3:406. 4) Sastry
M et al, PLoS One. 2017;12:e0186854. 5) Alessandrini F et al, Front Immunol. 2020;11:575936. 6) Daley MF et al, Acad Pediatr . 2023 Jan -Feb;23(1):37 -46.
KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH
•N=14337 with eczema: 6.0% developed persistent asthma
•N=312654 without eczema: 2.1% developed persistent asthma
•Median vaccine -associated aluminum:
oEczema cohort=4.18 mg
oNo eczema cohort=4.18 mg
12 Schedule and SafetyRef: Daley MF et al, Acad Pediatr . 2023 Jan -Feb;23(1):37 -46. Results: Aluminum and Asthma Study
KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH
Crude
Incidence Rate
of Asthma by
Quantity of
Vaccine-
Associated
Aluminum
13
 Schedule and SafetyRef: Daley MF et al, Acad Pediatr . 2023 Jan -Feb;23(1):37 -46.
KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH
Association between Cumulative Vaccine -Associated
Aluminum and Persistent Asthma
Notes: Cox proportional hazards analyses; separate models for eczema and no eczema cohorts; other covariates included number of outpatient visits; number of ED
visits; child’s race/ethnicity; medical complexity; VSD site; birth month and year. EGA, estimated gestational age.
14 Schedule and Safety
KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH
Aluminum and Asthma Study: Secondary Analyses
Notes: Cox proportional hazards analyses; separate models for eczema and no eczema cohorts; other covariates included number of outpatient visits; number of ED
visits; child’s race/ethnicity; medical complexity; VSD site; birth month and year
15 Schedule and Safety
KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH
•Small positive association between cumulative vaccine -associated aluminum
before 24 months and persistent asthma 24 -59 months
•Positive finding for children with and without eczema
•Secondary analyses: positive associations in some but not all analyses
•Study strengths: deliberate process; extensive feedback; large sample; VSD with
high data quality; sophisticated analyses
•Study limitations: no data on dietary/environmental aluminum exposure (although
little to none of ingested aluminum absorbed per recent AAP report); no data on
social determinants of health; unmeasured confounding; antigen effects
•The first step of a multi -step research processInterpretation: Aluminum and Asthma Study
16Ref: 1) Daley MF et al, Acad Pediatr . 2023 Jan -Feb;23(1):37 -46. 2) Corkins MR, AAP Committee on Nutrition. Pediatrics. 2019;144:e20193148.
Schedule and Safety
KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH
Asthma Prevalence among Children <18 years of Age:
United States, 1980 –2020
17 Schedule and Safety0.02.04.06.08.010.012.0
1980 1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002 2004 2006 2008 2010 2012 2014 2016 2018 2020
YearPCV7DTaP
replaces DTPHib
Hep BHep A
(high incidence)
Hep A
(national)DTaP-Hep B-IPV
(PediarixTM)DTaP-IPV-Hib
(Pentacel ®)
PCV13
replaces PCV7Percent
(%)
Ref: The data from 1980 -1996 and 2001 -2020 are from National Health Interview Survey ( NHIS): 1) 1980 –1996 data are from Akinbami LJ, Schoendorf
KC, Parker J. Am J Epidemiolol . 2003. 2) 2001 –2020 data are from https://www.cdc.gov/asthma/nhis/default.htm
KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH
•Denmark national databases (Dr. Anders Hviid presentation at ACIP)
•New study in VSD:
oCohort: larger cohort, longer follow up time
oExposure: aluminum before 12 months of age
oEczema: treat eczema as covariate
oOutcome: asthma diagnosed at a later age (60 through 84 months of age);
asthma diagnosed earlier may represent viral -induced wheezing (not asthma)
•Additional consideration of other data sources which could help
assess relationship between vaccine aluminum exposure and
subsequent asthma riskFurther Investigations, Vaccine Aluminum and Risk of Asthma
18 Schedule and Safety
KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH
•Totality of available evidence continues to support the safety of the routine childhood
vaccination schedule
•Existing federal vaccine safety surveillance systems robust and responsive to concerns
expressed by parents of young children
•Precipitated by 2013 IOM Report on schedule, new field of study is being developed:
oExamine cumulative, repeated exposures to vaccines and vaccine ingredients
oExamine long -term health outcomes
•At time of IOM Report, few studies of the safety of the schedule “as a whole”
•Evidence accumulating around specific testable hypotheses; results which can be
communicated to parents
•Additional studies related to aluminum and asthma risk planned and ongoing
•Benefits of vaccination strongly outweigh known and potential risksThe Schedule and Safety: Broader Context
19 Schedule and Safety
THANK YOU
20

Summary: The Childhood Immunization Schedule and  Safety: Studies in the Vaccine Safety Datalink Matthew F. Daley MD Advisory Committee on Immunization Practices, June 23, 2023 KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH •No conflicts of interest to disclose •The findings in this presentation are those of the speaker and do not  necessarily represent the official position of the Centers for Disease  Control and PreventionDisclaimers Schedule and Safety 2 KAISER PERMANENTE INSTITUTE FOR HEALTH…


03 VaxSafety Hviid 508

Preliminary evaluation of aluminum content in childhood vaccines and risk of
asthma in a Danish nationwide cohort
Prof. Anders Hviid, Statens Serum Institut, Copenhagen, Denmark
Advisory Committee on Immunization Practices, June 23, 2023

Study cohort
•Born in Denmark 2009 -2016
•Study start 1/1 2011 ; study end 12/31 2018
•Follow -up from 2 to 5 -years -of-age
•Exposure and outcome data from nationwide -
registers
•N=470,477 children
2
The Danish schedule
3Danish schedule
3 mo.:   DiTePeIPVHib1 + PCV1
5 mo.:   DiTePeIPVHib2 + PCV2
12 mo.: DiTePeIPVHib3 + PCV3
15 mo.: MMR1
4 yrs:     MMR2
5 yrs:     DiTePeIPV booster
12 yrs:   HPV1 and HPV2

Cumulative aluminium exposure
4
Asthma outcome definitions
•Hospital contacts, ICD-10 J45 (asthma), J46 (status asthmaticus) , in-and
outpatients
•Community anti -asthmatics prescriptions: Inhaled corticosteroids (n=2), short -
acting beta -agonists (n=3), montelukast (n=2), long -acting beta -agonists (n=1)
•Primary outcome:  Hospitalization and/or anti -asthma drug use
•Exclusion criteria: Any prescriptions orhospitalizations before the age of 2.
•Date of outcome: First among the above events
5
Secondary outcomes -latent class analysis
Inpt.           Outpt .           SABA ICS            LABA        MON  Cluster 1: ” Montelukast ”
6.5%
Cluster 2: ”SABA”
23.3%
Cluster 3: ” Hospitalization ”
7.9%
Cluster 4: ” Inhaled corticosteroids +/-SABA”
62.3%
6SABA: Short-acting beta agonist; LABA: Long-acting beta agonist; ICS: Inhaled corticosteroid; MON: Montelukast.
Cohort characteristics
7Cumulative aluminum received by 2-yrs- of-age
KOEN: Sex; OPR: Mothers country of origin .
Main Results –Hosp. or anti -asthma medication
Table : Association between cumulative aluminum received through vaccines by age 2 and asthma by
age 5 among 470477 Danish children born 2009 to 2016 and followed 2011 to 2018
 Asthma cases1 Person -years of follow -up Hazard ratio (95% CIs)2
0 mg  62 13,082.00  0.90 (0.68 to 1.19)
<2.25mg  327 65,167.16  1.00 ( - to -)
2.25mg  446 78,643.45  1.07 (0.92 to 1.24)
>2.25mg -<3.375mg  1092  206,053.42  1.00 (0.88 to 1.14)
3.375mg  3096  597,727.75  0.98 (0.86 to 1.11)
>3.375mg  838 165,528.63  1.00 (0.84 to 1.18)
1Hospitalization and/or anti -asthma prescription drug use
2Adjusted for sex, year of birth, maternal country of origin, and MMR vaccination by age 2.

8Aluminum
Main Results –Dose -response
9
Association between aluminum and asthma clusters
10Hazard Ratio* (95% CI)
* Adjusted for sex, year of birth , maternal country of origin , MMR vaxbefore 2-yrs-of-age Comparing >3.375mg
cumulative aluminum received
through vaccines by 2-yrs- of-age
to <2.25mg
Limitations
11•Limited variability in cumulative aluminum
•Validity of using asthma diagnosis and anti -
asthma drug use before 5 -yrs-of-age
Take -away
•No support for an association between
aluminium in vaccines and asthma by 5 -
yrs-of-age in Denmark
12

Summary: Preliminary evaluation of aluminum content in childhood vaccines and risk of  asthma in a Danish nationwide cohort Prof. Anders Hviid, Statens Serum Institut, Copenhagen, Denmark Advisory Committee on Immunization Practices, June 23, 2023    Study cohort •Born in Denmark 2009 -2016 •Study start 1/1 2011 ; study end 12/31 2018 •Follow -up from 2 to 5 -years -of-age •Exposure and outcome data from nationwide - registers •N=470,477 children 2 The Danish schedule 3Danish schedule 3 mo.:  …


01 COVID Daley 508

cdc.gov/coronavirus
ACIP COVID -19 Vaccines Work Group
Dr. Matthew F. Daley, Work Group Chair
June 23, 2023
▪COVID -19 vaccine program updates
▪Vaccine safety updates
▪Vaccine effectiveness data updates
▪Data and Work Group considerations for updates to vaccine policy
–Single bivalent vaccine dose for most persons aged ≥6 years
–Bivalent vaccines for children aged 6 months –5 years
–Optional additional bivalent doses for persons aged ≥6 months who are moderately or
severely immunocompromised and adults aged ≥65 years
▪Clinical considerations updateApril ACIP COVID-19 Meeting Review
April 19, 2023
2
▪Epidemiology of COVID -19, including among pregnant people and infants
▪Vaccine effectiveness (VE) updates
▪Discussion of populations who still need a primary seriesACIP COVID-19 Work Group Meeting Review
May– June 2023
3
▪June 15, 2023: FDA’s Vaccines and Related Biological Products Advisory
Committee (VRBPAC) met to discuss strain selection for updated COVID -19
vaccines
–Based on the totality of the evidence presented, FDA advised
manufacturers to develop updated COVID -19 vaccines with a monovalent
XBB.1.5 composition
–Anticipate updated vaccine doses will be broadly available in the fall
–Following updated vaccine authorizations, ACIP will review evidence to
inform updated recommendationsCOVID-19 vaccine update:
VRBPAC Meeting
4https://www.fda.gov/vaccines-blood-biologics/updated-covid- 19-vaccines-use-united-states-beginning-fall- 2023
Agenda:
Friday June 23, 2023
•
•
•Updates to COVID-19 epidemiology and vaccine
effectivenessDr. Havers (CDC)
Dr. Galang (CDC)
Dr. Link -Gelles (CDC)
Infection-induced and hybrid immunity Dr. Jones (CDC)
Summary and Work Group considerations Dr. Wallace (CDC)
ACIP members
▪
▪
▪
▪
▪
▪
▪
▪
▪
▪
▪
▪
▪
▪▪
▪
▪
▪
▪
▪
▪
▪
▪
▪
▪
▪▪ Matthew Daley (chair)
Beth Bell
Grace Lee
Keipp Talbot
Oliver Brooks
Ex-officio/government members
FDA: Rachel Zhang, Lucia Lee, Anuja Rastogi
NIH: Chris Roberts
IHS: Uzo Chukwuma
CMS: Jeff Kelman
BARDA: Christine Oshansky
HHS: Valerie Marshall
CDC: Alan Lam
CDC Leads
Sara Oliver
Megan WallaceWork Group members
6Liaisons
AAFP: Jonathan Temte
AAP: Sean O’Leary
ACOG: Denise Jamieson (primary),
Laura Riley (alternate)
ACP: Jason Goldman
ADS: Emily Kahn
AGS: Ken Schmader
AIM: Rob Shechter (primary),
Jane Zucker (alternate)
AMA: Sandra Fryhofer
ANA: Ruth Francis (alternate)
APhA: Michael Hogue
ASTHO: Marcus Plescia
CSTE: Paul Cieslak, Christine Hahn
IDSA: Jeff Duchin (primary)Liaisons, cont’d
NACCHO: Matt Zahn (primary),
Jeff Duchin (alternate)
▪NACI: Matthew Tunis (primary),
Nicole Forbes (alternate)
▪NFID: Bill Schaffner (primary),
Marla Dalton (alternate)
▪NMA: Patricia Whitley-Williams
▪SHEA: Preeti Mehrotra
Marci Drees (alternate)
Consultants
▪Ed Belongia
▪Hank Bernstein
▪Kathy Edwards
▪Robert Hopkins
▪Lisa Jackson
▪Kathy Kinlaw
▪Dayna Matthew ▪Jennifer Nelson
▪Kathleen Neuzil
▪Stanley Perlman
▪Peter Szilagyi
▪Sarah Meyer
▪Elisha Hall
▪Danielle Moulia
▪Lauren Roper
▪Hannah Rosenblum
▪Katherine Fleming -Dutra
▪Monica Godfrey
▪Susan Goldstein
▪Mary Chamberland
▪Stephen Hadler
▪JoEllen Wolicki
▪Melinda Wharton
▪Jessica MacNeil
▪Amanda Cohn
▪Ruth Link -GellesCDC participants
7▪Amadea Britton
▪Carolyn Bridges
▪Allison Ciesla
▪Nicole Dowling
▪Ashley Fowlkes
▪Heather Scobie
▪Natalie Thornburg
▪Tom Shimabukuro
▪John Su
▪Karen Broder
▪Rita Helfand
▪Jefferson Jones
▪Yvonne Bolen
▪Samuel Graitcer
▪Lisa Grohskopf▪Laura Steinhardt
▪Ryan Wiegand
▪Patricia Yu
▪Yon Yu▪Katherina Grusich
▪Aaron Hall
▪Terri Hyde
▪Kristen Nordlund
▪Sierra Scarbrough
▪Andrew Kroger
▪Lauri Markowitz
▪Noelle -Angelique Molinari
▪Michael McNeil
▪Morgan Najdowski
▪Ismael Ortega -Sanchez
▪Pragna Patel
▪Amanda Payne
▪Georgina Peacock
▪Jose Romero
For more information, contact CDC
1-800-CDC-INFO (232-4636)
TTY:  1- 888- 232-6348    www.cdc.gov
The findings and conclusions in this report are those of the authors and do not necessarily represent the
official position of the Centers for Disease Control and Prevention.
Thank you!

Summary: cdc.gov/coronavirus ACIP COVID -19 Vaccines Work Group Dr. Matthew F. Daley, Work Group Chair June 23, 2023 ▪COVID -19 vaccine program updates ▪Vaccine safety updates ▪Vaccine effectiveness data updates  ▪Data and Work Group considerations for updates to vaccine policy –Single bivalent vaccine dose for most persons aged ≥6 years  –Bivalent vaccines for children aged 6 months –5 years –Optional additional bivalent doses for persons aged ≥6 months who are moderately or  severely…