01 DT Hughes Santoli 508

National Center for Immunization & Respiratory Diseases
VFC Resolution Update: Tetanus and Diphtheria Toxoid Containing Vaccines
Michelle Hughes
Division of Bacterial Diseases
National Center for Immunization and
Respiratory DiseasesJeanne Santoli
Immunization Services Division
National Center for Immunization and
Respiratory Diseases
February 2024
Background
Background
•CDC recommends a primary series of 5 DTaP vaccines for children <7
years
•For children aged <7 years who developed a contraindication to pertussis -containing vaccines, CDC previously recommended DT instead
of DTaP
•The sole DT vaccine manufacturer in the U nited States  discontinued DT
production
•Last lot expired in April 2023
•No DT vaccin e is av ailable in the United States
Contraindication specific to pertussis vaccine
component
•The only contraindication specific to the pertussis component in DTaP is
encephalopathy within 7 days of vaccination, not attributed to another cause.
•Exact numbers are unknown, but occurrence of this adverse reaction is extremely rare.
•CDC issued updated vaccination guidance for young children with a contraindication to pertussis -containing vaccines.
Guidance
•CDC recommends young children receive DTaP as the first dose in the
diphtheria, tetanus, and pertussis childhood vaccination series.
•CDC recommends continued use of DTaP unless a contraindication to pertussis -containing vaccines develops.
•For young children who develop a contraindication to pertussis -
containing vaccines, vaccine providers may administer Td for all recommended remaining doses in place of DTaP .
Uncertain impact on diphtheria protection
•Td is licensed for ages ≥7 years
•Td contains a lower dose of diphtheria toxoid compared to DT
•Limited data suggest that low -dose diphtheria toxoid -containing
vaccines may not reliably generate a protective diphtheria
seroresponse.
https://www.cdc.gov/vaccines/vpd/dtap- tdap -td/hcp/td- offlabel.html

VFC Resolution Updates
•MassBiologics  has discontinued production of their Td vaccine, TdVax.TM Grifols, who is the
exclusive distributor for TdVax,TM expects to have product available through approximately
June 2024.
•Sanofi, who manufacturers Tenivac ,® the only other US- licensed Td vaccine, is taking steps to
augment their available supply of Td for the US.  However, it is anticipated that the supply of
Td vaccine in the US market will be constrained during 2024.  Temporary ordering controls
have been put into place in the public and private sectors to help manage the gap in supply.
•Tdap vaccine is available from both US- licensed manufacturers without supply constraints at
this time.
•Based on the rarity of developing a contraindication to pertussis -containing vaccines,  the
temporarily constrained supply of Td vaccine is not anticipated to prevent providers from
utilizing Td vaccine for these children in the VFC program. Td Vaccine Supply Update
The purpose of this resolution is to (1) add Td vaccine for use in children < 7 years of
age for whom receipt of the pertussis component is contraindicated and to (2) update the language regarding the Tdap booster to align with ACIP recommendations. Purpose of the Resolution
Children and adolescents aged 6 weeks through 18 years. Eligible Groups
Vaccines containing tetanus toxoid, diphtheria toxoid, and acellular pertussis antigens
recommend for use in persons aged <7 years.Recommended Schedule and Intervals (1)
Vaccine Type Vaccine Brand (1) Age for approved use in the
routine schedule (2)
2 mos 4
mos6
mos15-18
mos4-6 yrs
(3)
DTaP DTaP (4) Daptacel X X X X X
DTaP (4) Infanrix X X X X X
Combination
vaccines with
DTaPDTaP -HepB- IPV (4, 5) Pediarix X X X
DTaP -IPV/Hib (4, 6) Pentacel X X X X
DTaP -IPV-Hib-HepB (4,
7)  Vaxelis X X X
DTaP -IPV (8) Kinrix X
DTaP -IPV (8) Quadracel X
Td Td (9) Tenivac  X X X X
Td Td (9) TdVax  X X X X
(1)The use of brand names is not meant to preclude the use of other comparable licensed
vaccines.
(2)Minimal intervals: Dose 1 to 2: 4 weeks. Dose 2 to 3: 4 weeks. Dose 3 to 4: 6 months. Dose 4 to 5: 6 months. For more information on age for use in catch -up immunization schedules please
see: https://www.cdc.gov/vaccines/schedules/hcp/imz/catchup.html

(3)The fifth dose is not necessary if the fourth dose was given after the fourth birthday.
(4)FDA-approved for use in infants as young as 6 weeks.
(5)FDA-approved for use through age 6 years (prior to 7th birthday). The combined DTaP-HepB -IPV
vaccine may be used when any component of the combination is indicated, and if the other
components are not contraindicated. Approved for the primary series only (Doses 1 -3). For
adequate immune response, the last dose of hepatitis B vaccine should be given at ≥24 weeks
of age and therefore this combination vaccine should not be administered as a complete
primary series on an accelerated schedule at 4 -week intervals for prevention of pertussis.  Recommended Schedule and Intervals (2)
(6) FDA-approved for use through age 4 years (prior to 5th birthday). The combined DTaP-IPV/Hib
vaccine may be used when any component of the combination is indicated, and if the other
components are not contraindicated. Approved for the primary series and first booster dose (Doses
1-4). The combined DTaP -IPV/Hib vaccine is not indicated for children 5 years of age and older.
(7) FDA-approved for use through age 4 years (prior to 5th birthday). The combined DTaP-IPV -Hib-
HepB vaccine may be used when any component of the combination is indicated, and if other
components are not contraindicated.  Approved for the primary series only (Doses 1 -3). For
adequate immune response, the last dose of hepatitis B vaccine should be given >24 weeks of age
and therefore this combination vaccine should not be administered as a complete primary series
on an accelerated schedule at 4 -week intervals for prevention of pertussis.
(8) The combined DTaP -IPV vaccines may be used when any component of the combination is
indicated, and if the other components  are not contraindicated. Only approved for the booster
dose at age 4 through 6 years.  Earlier doses should use another vaccine.
(9) Use tetanus toxoid - and diphtheria toxoid-containing vaccine if encephalopathy not attributable to
another identifiable cause occurs within 7 days of administration of previous dose of pertussis -
containing vaccine. For more information on the use of Td in children <7 please see: About Young
Children with a Contraindication to Pertussis -Containing Vaccines | CDCRecommended Schedule and Intervals (3)
Vaccines containing tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis
antigens recommended for use in persons aged 7– 18 years. Recommended Schedule and Intervals (4)
Vaccine Type Brand
Tdap (1, 2, 3, 4) Adacel
Boostrix
Td (4, 5, 6) Tenivac
TdVax
(1)The use of brand names is not meant to preclude the use of other comparable licensed
vaccines.
(2)Persons aged 11 -18 years should receive a single booster dose of Tdap, preferably at a
preventive care visit at ages 11- 12 years.  The booster dose is not necessary if the Tdap
dose was given after the ninth birthday.
(3)Catch -up immunization:  Persons aged 7- 18 years who have never been vaccinated
against pertussis, tetanus, or diphtheria should receive a series of three tetanus and
diphtheria toxoid -containing vaccines, which includes at least 1 dose of Tdap. The
preferred schedule is a dose of Tdap, followed by a dose of either Td or Tdap at least 4
weeks afterward and another dose of either Td or Tdap 6 to 12 months later. Persons
aged 7- 18 years who are not fully immunized against pertussis, tetanus, or diphtheria
should receive one dose of Tdap (preferably the first) in the catch -up series; if
additional tetanus toxoid -containing doses are required, either Td or Tdap vaccine can
be used. The catch -up immunization schedule and minimum intervals between doses
are available at: https://www.cdc.gov/vaccines/schedules/hcp/child- adolescent.html  Recommended Schedule and Intervals (5)
(4) Adolescents who are pregnant should receive Tdap, irrespective of past history of Tdap receipt.
Tdap should be administered from 27 through 36 weeks’ gestation, preferably during the earlier part of this time period, although it may be administered at any time during pregnancy. If an adolescent did not receive Tdap during her current pregnancy and did not receive a prior dose of Tdap ever, then Tdap should be administered immediately postpartum.  If an adolescent did not receive Tdap during her current pregnancy but did receive a prior dose of Tdap, then she should not receive a dose of Tdap postpartum.
(5) Tetanus prophylaxis for wound management: A tetanus toxoid –containing vaccine is indicated as
part of wound management if more than five years has passed since the last tetanus toxoid –
containing vaccine dose. If a tetanus toxoid –containing vaccine is indicated for persons aged ≥11
years, Tdap is preferred for persons who have not previously received Tdap or whose Tdap history is unknown. If a tetanus toxoid–containing vaccine is indicated for a pregnant woman,
Tdap should be used. For nonpregnant persons with documentation of previous vaccination with
Tdap, either Td or Tdap can be used if a tetanus toxoid–containing vaccine is indicated.
(6) Td should be used if encephalopathy not attributable to another identifiable cause occurs within
7 days of administration of a previous dose of pertussis -containing vaccine. Recommended Schedule and Intervals (6)
Recommended Dosage
Refer to product package inserts available at:
https://www.fda.gov/vaccines -blood- biologics/vaccines/vaccines -licensed- use- united -
states
Contraindications/PrecautionsContraindications and precautions can be found at:  https://www.cdc.gov/mmwr/volumes/67/rr/rr6702a1.htm
 Dosage and Contraindications/Precautions
[If an ACIP recommendation regarding diphtheria, tetanus, and pertussis vaccination is
published within 6 months following this resolution, the relevant language above (except in the eligible groups sections) will be replaced with the language in the
recommendation and incorporated by reference to the publication URL.]  Statement Regarding Update Based on Published
Documents

Summary: National Center for Immunization & Respiratory Diseases VFC Resolution Update: Tetanus and Diphtheria Toxoid Containing Vaccines Michelle Hughes Division of Bacterial Diseases National Center for Immunization and  Respiratory DiseasesJeanne Santoli Immunization Services Division National Center for Immunization and  Respiratory Diseases February 2024 Background Background •CDC recommends a primary series of 5 DTaP vaccines for children <7  years •For children aged <7 years who developed a…


02 influenza Frutos 508

National Center for Immunization & Respiratory Diseases
Interim Estimates of 2023–24 Seasonal Influenza Vaccine
Effectiveness
Aaron M. Frutos, PhD, MPH
On behalf of CDC Influenza Vaccine Effectiveness Collaborators
Advisory Committee on Immunization Practices
February 28, 2024
CDC Influenza Vaccine Effectiveness Networks
Four networks to evaluate vaccine effectiveness (VE) against laboratory -
confirmed influenza for children, adolescents, and adults in the
outpatient and inpatient settings
3CDC Influenza Vaccine Effectiveness Networks
Investigating Respiratory Viruses in the Acutely Ill (IVY)
New Vaccine Surveillance Network (NVSN)
U.S. Flu Vaccine Effectiveness Network (US Flu VE)
Virtual SARS -CoV-2, Influenza, and Other respiratory viruses Network (VISION)
VISION
IVYNVSN
4These networks include all ages across settings
AgeSettingOutpatient
clinic
HospitalizationEmergency
department/
urgent careUS Flu VE
Adults
(≥18 years)Children and adolescents
(6 months – 17 years)
NVSN
5NVSN: all settings
AgeSettingOutpatient
clinic
HospitalizationEmergency
department/
urgent care
Adults
(≥18 years)Children and adolescents
(6 months – 17 years)
NVSN
6US Flu VE: Outpatient clinic and ED/UC
AgeSettingOutpatient
clinic
HospitalizationEmergency
department/
urgent careUS Flu VE
Adults
(≥18 years)Children and adolescents
(6 months – 17 years)
NVSN
7VISION: ED/UC & hospitalization
AgeSettingOutpatient
clinic
HospitalizationEmergency
department/
urgent careUS Flu VE
Adults
(≥18 years)Children and adolescents
(6 months – 17 years)VISION
IVY
8IVY: hospitalization
AgeSettingOutpatient
clinic
HospitalizationEmergency
department/
urgent care
Adults
(≥18 years)Children and adolescents
(6 months – 17 years)
IVY
9US Flu VE: Outpatient clinic and ED/UC
AgeSettingOutpatient
clinic
HospitalizationEmergency
department/
urgent care
Adults
(≥18 years)Children and adolescents
(6 months – 17 years)US Flu VE
IVY
10VISION: ED/UC & hospitalization
AgeSettingOutpatient
clinic
HospitalizationEmergency
department/
urgent care
Adults
(≥18 years)Children and adolescents
(6 months – 17 years)US Flu VE
VISION
VISION
IVYNVSN
11These networks include all ages across settings
AgeSettingOutpatient
clinic
HospitalizationEmergency
department/
urgent careUS Flu VE
Adults
(≥18 years)Children and adolescents
(6 months – 17 years)Outpatient
12CDC influenza VE networks include patients from 22
states
NVSN
IVY
US Flu VE
VISION

132023- 2024 Influenza VE Methods
Enrollees: Have acute respiratory illness
Dates of enrollment: Fall 2023-  Early 2024
Design: Test-negative design
•Comparing vaccination odds among case patients with influenza confirmed by molecular assay
versus control patients testing negative for influenza and SARS- CoV-2
•Vaccination status: receipt of any 2023 –24 seasonal flu vaccine according to medical records,
immunization registries, claims data, and/or self -report
142023- 2024 Influenza VE Methods
Analysis : VE = (1 – adjusted OR) x 100%
•Adjusted for geographic region, age, calendar time of illness
•IVY , US Flu VE, and VISION also adjusted for sex and race and ethnicity
•US Flu VE also adjusted for days between illness onset and enrollment and self -reported
general health status.
•VE estimates were calculated for influenza A subtypes A(H1N1)pdm09 and A(H3N2) when possible
•Subtype not available for VISION
•VE was not estimated for some age groups and settings when sample size was small or when
models did not converge
Pediatric VE
(aged 6 months –17 years)
16Pediatric VE against any influenza
Influenza test result by influenza vaccination
status, no. vaccinated/Total (%)
Influenza -positive Influenza -negative VE (95% CI)
NVSN (Outpatient) 123/622 (20) 793/2,577 (31) 59 (48, 67)
US Flu VE (Outpatient) 29/283 (10) 182/736 (25) 67 (48, 80)
VISION (Outpatient) 961/6,068 (16) 4,579/15,274 (30) 60 (57, 64)
NVSN (Inpatient) 29/128 (23) 543/1,321 (41) 61 (40, 75)
VISION (Inpatient) 21/113 (19) 299/921 (32) 52 (16, 72)
17Pediatric VE against any influenza

18Pediatric VE against influenza A

19Pediatric VE against influenza A(H1N1)pdm09

20Pediatric VE against influenza A(H3N2)

21Pediatric VE against influenza B

Adult VE
(aged ≥18 years)
23Adult VE against any influenza
Influenza test result by influenza vaccination
status, no. vaccinated/Total (%)
Influenza -positive Influenza -negative VE (95% CI)
US Flu VE (Outpatient) 177/568 (31) 803/1,807 (44) 33 (16, 47)
VISION (Outpatient) 4,501/18,385 (24) 21,356/52,657 (41) 49 (47, 51)
IVY (Inpatient) 200/632 (32) 1,517/3,872 (39) 44 (32, 54)
VISION (Inpatient) 728/1,839 (40) 7,425/14,168 (52) 41 (34, 47)
24Adult VE against any influenza

25Adult VE against influenza A

26Adult VE against influenza A(H1N1)pdm09

27Adult VE against influenza A(H3N2)

28Adult VE against influenza B

Adult (aged ≥65) VE
30Adult (aged ≥65) VE against any influenza
Influenza test result by influenza vaccination
status, no. vaccinated/Total (%)
Influenza -positive Influenza -negative VE (95% CI)
US Flu VE (Outpatient) 41/79 (52) 300/439 (68) 51 (14, 72)
VISION (Outpatient) 1,944/3,687 (53) 12,162/19,571 (62) 41 (36, 45)
IVY (Inpatient) 113/249 (45) 938/1,945 (48) 42 (23, 56)
VISION (Inpatient) 531/1,066 (50) 6,058/10,118 (60) 42 (34, 50)
31Adult (aged ≥65) VE against any influenza

32Adult (aged ≥65) VE against influenza A

33Adult (aged ≥65) VE against influenza B

Discussion
35Summary of four CDC influenza VE networks
Vaccination with a 2023 -24 influenza vaccine reduced the risk  for medically
attended influenza outpatient visits and hospitalizations  among children,
adolescents, and adults across 22 US States
Vaccination was effective against both influenza A (mostly subtype
A(H1N1)pdm09) and B (lineage Victoria) viruses  that have circulated this season
Results were consistent across networks
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.
Aaron M. Frutos, PhD, MPH
Influenza Division
National Center for Immunization and Respiratory Diseases
AFrutos@cdc.govWe’d like to thank our many
collaborators from CDC, IVY , NVSN,
US Flu VE, and VISIONThank you
37Overall VE (pediatric and adults) by season*
*Estimates are from US Flu VE except for 2022 -23 which are from a study from WI

Summary: National Center for Immunization & Respiratory Diseases Interim Estimates of 2023–24 Seasonal Influenza Vaccine  Effectiveness Aaron M. Frutos, PhD, MPH On behalf of CDC Influenza Vaccine Effectiveness Collaborators Advisory Committee on Immunization Practices February 28, 2024 CDC Influenza Vaccine Effectiveness Networks Four networks to evaluate vaccine effectiveness (VE) against laboratory - confirmed influenza for children, adolescents, and adults in the  outpatient and inpatient settings …


03 influenza Zhu 508

1Sophie Zhu, PhD, presenting on behalf of the study team
Epidemic Intelligence Service Officer
California Department of Public Health
Influenza VEData: Interviews,
electronic health records
New: California public
health dataMultiple considerations for vaccine
effectiveness (VE) calculation
Populations:
Pediatric, hospitalizedCare settings
2
New requirements for data reporting in
California
•1/1/23: Influenza vaccination records  became
reportable to the California Immunization
Registry (CAIR)
3•6/15/23: All negative influenza results (in
addition to previously reportable positive
influenza results) became reportable to the
California Reportable Disease Information
Exchange ( CalREDIE )
California VE Calculation
Attribute California
Data source Mandatory influenza results and influenza immunization records
Date available VE estimates and data available each December or earlier
Outcome(s) Laboratory -confirmed influenza using nucleic acid amplification
tests (NAAT)
Population(s) Californians tested for influenza using NAAT from diverse care
settings
4
Methods
5
•Inclusion criteria: California residents aged ≥6 months with molecular tests for
influenza (A/B) captured by the state electronic laboratory reporting system
•Dates: October 1, 2023 —January 31, 2024
•Vaccination status: documented dose of seasonal influenza vaccine in CAIR ≥14
days before testing
•Deduplicate results for persons with multiple records
•Remove results from laboratories weekly with ≥50% positive due to suspected
underreporting of negative results (<5% of data)
•Analysis:  VE = (1 – adjusted OR) x 100%
•Mixed -effects logistic regression model adjusted for age, race, ethnicity,
testing week (random effect), and county (random effect)
6Methods: unmatched case -control study
Number of influenza detections by type and subtype detected in RLN
laboratories and percentage of specimens testing positive at clinical
sentinel laboratories – 2023 -2024 season to date
7

Overall No. (%) Influenza positive No. (%) Influenza negative No. (%)
Total 678,422 (100) 77,501 (11.4) 600,921 (88.6)
Age ( yrs, median) 42 (17 –66) 31 (10 –52) 44 (19 –68)
Race
American Indian or Alaska Native
Asian
Black or African American
Native Hawaiian or Pacific Islander
White
Multiple Races
Other
Unknown2,919 (0.4)
53,419 (7.9)
40,069 (5.9)
2,878 (0.4)
301, 779 (44.5)
1,381 (0.2)
131,284 (19.4)
144,693 (21.3)326 (0.4)
6,252 (8.1)
4,033 (5.2)
300 (0.4)
29,908 (38.5)
130 (0.2)
16,098 (20.8)
20,454 (26.4)2,593(0.5)
47,167 (7.8)
36,036 (6.0)
2,578 (0.4)
271,871 (45.2)
1,251 (0.2)
115,186 (19.2)
124,239 (20.7)
Ethnicity
Hispanic or Latino
Not Hispanic or Latino
Unknown159,676 (23.6)
386,200 (56.9)
132,546 (19.5)21,309 (27.4)
38,653 (49.9)
17,539 (22.7)138,367 (23.1)
347,547 (57.8)
115,007 (19.1)
Vaccinated
Overall
Vaccinated during Oct. 1 –31
Vaccinated during Nov. 1 –30
Vaccinated during Dec. 1 –31
Vaccinated during Jan. 1 –31190,313 (28.1)
11,073 (13.1)
39,497 (25.3)
69,884 (30.1)
69,859 (33.9)13,905 (17.9)
93 (6.5)
1,357 (12.5)
7,104 (17.6)
5,351 (21.4)176,408 (29.3)
10,980 (13.2)
38,140 (26.3)
62,780 (32.7)
64,508 (35.6)Participant characteristics
8
Influenza vaccines protect against laboratory -
confirmed influenza
Influenza positive Influenza negative Adjusted VE*
Total Vaccinated no.
(%)Total Vaccinated no.
(%)% (95% CI)
Influenza A and B**
Overall 75,876 13,629 (18) 600,921 176,408 (29) 45 (44 –46)
<18 years 28,914 3,744 (13) 147,047 32,791 (22) 56 (54 –57)
18–49 years 26,435 3,334 (13) 189,129 36,171 (19) 48 (46 –50)
50–64 years 10,861 2,575 (24) 96,148 28,579 (30) 36 (33 –39)
≥65 years 9,666 3,976 (41) 168,597 78,867 (47) 30 (27 –33)
Study period: October 1, 2023 – January 31, 2024.
*VE was estimated using an unmatched case -control study as 100% x (1 -aOR) where aOR is the ratio of odds of vaccination among influenza
positive cases versus influenza negative controls. ORs were estimated using mixed -effects logistic regression with adjustment fo r age, race,
ethnicity as fixed effects and enrollment week and county of residence as random effects.
**VE for unknown influenza types was not calculated because of small sample size, and unknown influenza type results were exclu ded from
overall influenza A and B VE estimation.
9
VE against influenza A was lower but still
protective in all age groups
Influenza positive Influenza negative Adjusted VE*
Total Vaccinated no.
(%)Total Vaccinated no.
(%)% (95% CI)
Influenza A
Overall 68,716 13,118 (19) 600,921 176,408 (29) 42 (41 –43)
<18 years 25,393 3,517 (14) 147,047 32,791 (22) 52 (51 –53)
18–49 years 23,257 3,136 (14) 189,129 36,171 (19) 44 (42 –46)
50–64 years 10,546 2,532 (24) 96,148 28,579 (30) 35 (32 –38)
≥65 years 9,520 3,933 (41) 168,597 78,867 (47) 29 (26 –32)
Study period: October 1, 2023 – January 31, 2024.
*VE was estimated using an unmatched case -control study as 100% x (1 -aOR) where aOR is the ratio of odds of vaccination among influenza
positive cases versus influenza negative controls. ORs were estimated using mixed -effects logistic regression with adjustment fo r age, race,
ethnicity as fixed effects and enrollment week and county of residence as random effects.
10
VE against influenza B was highly protective
across most age groups
Influenza positive Influenza negative Adjusted VE*
Total Vaccinated no.
(%)Total Vaccinated no.
(%)% (95% CI)
Influenza B
Overall 7,160 511 (7) 600,921 176,408 (29) 76 (73 –78)
<18 years 3,521 227 (6) 147,047 32,791 (22) 79 (76 –82)
18–49 years 3,178 198 (6) 189,129 36,171 (19) 75 (71 –78)
50–64 years 315 43 (14) 96,148 28,579 (30) 67 (55 –76)
≥65 years 146 43 (29) 168,597 78,867 (47) 54 (33–67)
Study period: October 1, 2023 – January 31, 2024.
*VE was estimated using an unmatched case -control study as 100% x (1 -aOR) where aOR is the ratio of odds of vaccination among influenza
positive cases versus influenza negative controls. ORs were estimated using mixed -effects logistic regression with adjustment fo r age, race,
ethnicity as fixed effects and enrollment week and county of residence as random effects.
11
Cumulative VE — Oct. 1, 2023 –Jan. 31, 2024
Influenza positive Influenza negative Adjusted VE*
Total Vaccinated no.
(%)Total Vaccinated no.
(%)% (95% CI)
Influenza A and B**
October 31st 1,455 93 (6) 83,403 11,021 (13) 46 (34, 57)
November 30th 11,703 1,376 (12) 223,921 47,682 (21) 51 (48, 54)
December 31st 53,181 8,695 (16) 416,136 110,816 (27) 47 (46, 48)
Overall (January 31st) 75,876 13,905 (18) 600,921 176,408 (29) 45 (44, 46)
*VE was estimated using an unmatched case -control study as 100% x (1 -aOR) where aOR is the ratio of odds of vaccination among influenza
positive cases versus influenza negative controls. ORs were estimated using mixed -effects logistic regression with adjustment fo r age, race,
ethnicity as fixed effects and enrollment week and county of residence as random effects.
**VE for unknown influenza types was not calculated because of small sample size, and unknown influenza type results were exclu ded from
overall influenza A and B VE estimation.
12
Limitations
1.Likely incomplete documentation and reporting of mandatory vaccination and
testing
2.Cannot assess partial/full vaccination status for children aged <9 years
3.Lack of symptom information, test setting, and outcome status (illness,
hospitalization, or death)
4.Potential lack of generalizability across the US
5.Subtype information not available for positive influenza results
6.Lack of control for other confounders (health seeking behavior, pre -existing
conditions)
13
Summary
•Current seasonal influenza vaccines provide protection against
laboratory -confirmed influenza for persons aged ≥6 months
•Higher VE for influenza B & younger age groups (<18 years, 18 -49
years)
•Mandatory public health data can be leveraged to calculate timely in -
season influenza effectiveness as an additional estimate supporting
existing public health influenza efforts including vaccination messaging
•Useful to promote additional prevention measures prior to peak
•Prepare for increased hospital capacity
14
Acknowledgments
CDPH Division of Communicable Disease Control
Joshua Quint*
Tomás M. León*
Monica Sun*
Nancy J. Li*
Seema Jain*
Cora Hoover*
Robert Schechter*
Erin L. Murray*
Timothy Lo
Celeste Romano
15CDC NCIRD
Mark Tenforde*
Jessie Chung
Sascha Ellington
*co-authorCalifornia’s local
health
departments

Summary: 1Sophie Zhu, PhD, presenting on behalf of the study team Epidemic Intelligence Service Officer  California Department of Public Health Influenza VEData: Interviews,  electronic health records New: California public  health dataMultiple considerations for vaccine  effectiveness (VE) calculation Populations: Pediatric, hospitalizedCare settings 2 New requirements for data reporting in  California •1/1/23: Influenza vaccination records  became  reportable to the California Immunization  Registry…


04 influenza Creech 508

Safety of Live Attenuated
Influenza Vaccine in
Children with Asthma
C. Buddy Creech, MD, MPH
Edie Carell Johnson Chair and Professor, Pediatric Infectious Diseases
Director, Vanderbilt Vaccine Research Program
Vanderbilt University Medical Center
Nashville, Tennessee
Advisory Committee on Immunization Practices (ACIP) Meeting
February 28, 2024
Disclaimer
•The findings and conclusions in this presentation are those of the presenter and
do not necessarily represent the official position of the Centers for Disease Control and Prevention
•Mention of a product or company name is for identification purposes only and does not constitute endorsement by CDC
•This study was supported by the CDC Clinical Immunization Safety Assessment (CISA) Project
•Dr. Creech reports the receipt of consulting fees from Pfizer, Moderna, Sanofi, GSK, TD Cowen Investments, and CommenseBio ; grant support from Moderna;
and royalties from UpToDate. None are related specifically to influenza vaccines or asthma
2
Duke University
Amy Stallings, MD
Chris Todd, MPH
Sue Doyle, LPN
Lynn Harrington, RN, BSNLori Hendrickson, RN, BSNBeth Patterson, RN, BSN
Luis Ballon
Joyce Gandee
Erica SuarezCincinnati Children’s Hospital
Mary Allen Staat , MD, MPH
Carolyn Kercsmar , MD
Marilyn Rice, MSValerie Sackenheim , RN, CPN
Joe Sorter, BAJeanne Kleiman, BS, ALC, CCRPVanderbilt University Medical Center
C. Buddy Creech, MD, MPHAndrew Sokolow, MD
Kathryn Edwards, MD
Natalia Jimenez, PhD, MSCIShanda Phillips, RN, BSNKate Sokolow, RN, MSN
Braxton Hern, BS
Paula Campbell, MPHYuwei Zhu, MDCDC
Karen Broder, MDTheresa Harrington, MD, MPHTM (retired)
Frank DeStefano, MD, MPH (retired)
Lisa Grohskopf , MD, MPH
Oidda  Museru , RN, MPH
Suzanne Beavers, MD A. Patricia Wodi, MD

Bottom Line, Up Front
In a study of 142 children
with persistent asthma,
LAIV4 was not associated  with
increased frequency of asthma
exacerbations, increase in asthma -
related symptoms, or decrease in
peak expiratory flow rate (PEFR)
in the 6 weeks following vaccination
4

Ann Allergy Asthma
Immunol 2017
Vaccines 2017
In these studies, children with asthma who received LAIV were not found
to have a higher incidence of lower respiratory events
JACI 2020
6Study Population:
5 – 17-year -old
children with
persistent asthma
Primary Objective and Definitions
To compare the proportion of participants experiencing an asthma
exacerbation during the 42 days after LAIV4 vs. IIV4
•Scientific Hypothesis: LAIV4 is non-inferior to IIV4
•Null Hypothesis: Expressed statistically, the hypothesis was that the proportion of
children experiencing an asthma exacerbation in the LAIV4 group would be ≥10% higher than the proportion in the IIV4 group.
Persistent Asthma: Provider diagnosis of asthma + prescription of a long -
acting controller medication
•Note: This is distinct from intermittent asthma , in which children may have
intermittent, mild symptoms or require infrequent doses of albuterol
Asthma Exacerbation : An acute episode of progressively worsening
shortness of breath, cough, wheezing, chest tightness, or respiratory distress
for which the patient seeks medical attention or receives a new prescription for systemic corticosteroids.
7
Relevant Exclusion Criteria
•Acute illness (with or without fever) within 72 hours of enrollment or use
of antipyretics within 24 hours led to a temporary delay in vaccination
•Recent receipt of inactivated vaccine (14 days) or live vaccine (28 days) or planned receipt of any vaccine within 42 days of vaccination
•Children with immunosuppression, including those who had received 20 mg of prednisone (or greater) for more than 14 days in the previous month, were excluded.
•Children who had a life- threatening exacerbation in the previous 2 years or
any exacerbation in the month prior to enrollment
•Use of influenza- specific antiviral medication within 48 hours of enrollment
•Currently receiving aspirin
8
Additional Eligibility Issues
Post -menarchal  females had urine or serum pregnancy testing prior to
enrollment
For children 5 -8 years of age who required two doses of vaccine based
upon ACIP recommendations, enrollment could occur after either the
first or the second dose of vaccine.
•If enrollment occurred after the first dose, the study staff instructed the
family to delay 2nd vaccination until after study follow- up was completed
unless widespread influenza disease activity was detected in the community.
9
10

11
70% of participants were classified as having moderate or severe asthma
There were slightly more males than females (p=0.5)Black individuals comprised >30% of the study population; approximately 5% were Hispanic or Latino
In the 14 days following vaccination, we observed 3 exacerbations
among LAIV4 recipients and 4 in IIV4 recipients (3.9% vs. 5.7%, p=0.74)
In the 42 days following vaccination, we observed 8 exacerbations in
the LAIV4 group and 10 in the IIV4 group (10.8% vs. 14.7%, p=0.71)
12
Given that the upper bound for non- inferiority was 10% (0.1), a difference in
proportion of - 3.9% (CI: 90% CI:  - 0.15, 0.07) means that we can reject the null
hypothesis that LAIV4 is inferior to IIV4.
LAIV4 was not associated with increased asthma symptoms
13
No significant differences were seen when
comparing across age groups (5 -11 years of
age, 12 -17 years of age), study site, or
asthma severity (mild/moderate vs. severe)
PEFR: Peak Expiratory Flow Rate
Myalgia and sore throat were more common in IIV4 recipients
Strengths and Limitations of the Study
Strengths
•Multicenter, prospective, randomized, and controlled
•Enriched for children with persistent asthma and those with moderate to severe asthma
•Captured asthma symptoms in addition to asthma exacerbations and medical utilization
•Captured reactogenicity data
•Enrolled over two influenza seasons, increasing generalizability
Limitations
•Enrolled fewer participants than originally intended, but posterior power calculations revealed
adequate power (79%) to detect differences between groups
•Enrolled over two influenza seasons, leading to slightly different products
15
Summary and Conclusions
LAIV4 was not associated with increased asthma symptoms or
asthma exacerbations in the 14 - or 42 -days following immunization
Rates of reactogenicity were similar between IIV4 and LAIV4, though myalgia and sore throat were more common in the IIV4 arm
LAIV4 may be a suitable option for children ≥5 years with asthma, including moderate to severe asthma
16
Duke University
Amy Stallings, MD
Chris Todd, MPH
Sue Doyle, LPN
Lynn Harrington, RN, BSNLori Hendrickson, RN, BSNBeth Patterson, RN, BSN
Luis Ballon
Joyce Gandee
Erica SuarezCincinnati Children’s Hospital
Mary Allen Staat , MD, MPH
Carolyn Kercsmar , MD
Marilyn Rice, MSValerie Sackenheim , RN, CPN
Joe Sorter, BAJeanne Kleiman, BS, ALC, CCRPVanderbilt University Medical Center
C. Buddy Creech, MD, MPHAndrew Sokolow, MD
Kathryn Edwards, MD
Natalia Jimenez, PhD, MSCIShanda Phillips, RN, BSNKate Sokolow, RN, MSN
Braxton Hern, BS
Paula Campbell, MPHYuwei Zhu, MDCDC
Karen Broder, MDTheresa Harrington, MD, MPHTM (retired)
Frank DeStefano, MD, MPH (retired)
Lisa Grohskopf , MD, MPH
Oidda Museru, RN, MPHSuzanne Beavers, MD A. Patricia Wodi, MD

Discussion
18

Summary: Safety of Live Attenuated  Influenza Vaccine in  Children with Asthma C. Buddy Creech, MD, MPH Edie Carell Johnson Chair and Professor, Pediatric Infectious Diseases Director, Vanderbilt Vaccine Research Program Vanderbilt University Medical Center Nashville, Tennessee Advisory Committee on Immunization Practices (ACIP) Meeting February 28, 2024 Disclaimer •The findings and conclusions in this presentation are those of the presenter and  do not necessarily represent the official position of…


05 influenza grohskopf 508

National Center for Immunization & Respiratory Diseases
Influenza B/Yamagata Update
Lisa Grohskopf, MD, MPH
Advisory Committee on Immunization Practices
February 28, 2024
•Quadrivalent influenza vaccines introduced in 2013 -14 to provide broader coverage
of influenza B viruses.
–Quadrivalents contain one influenza B virus from each lineage (Victoria and Yamagata).
–Transition from trivalents to quadrivalents complete by the 2021 -22 influenza season.
•No confirmed influenza B/Yamagata viruses in global surveillance since March 2020.
•WHO and the FDA Vaccines and Related Biological Products Advisory Committee
(VRBPAC) have recommended excluding B/Yamagata from influenza vaccines.
•WHO has made recommendations for Northern Hemisphere 2024 -25 vaccines.
–Decisions regarding composition are made by individual national regulatory authorities.
•VRBPAC to discuss composition of 2024- 25 U.S. influenza vaccines on March 5, 2024. Influenza B/Yamagata and 2024 -25 Influenza Vaccines
2Recommended composition of influenza virus vaccines for use in the 2024 southern hemisphere influenza season (who.int)
Vaccines and Related Biological Products Advisory Committee October 5, 2023 Meeting Announcement - 10/05/2023 | FDA
Recommended composition of influenza virus vaccines for use in the 2024 -2025 northern hemisphere influenza season (who.int)
Vaccines and Related Biological Products Advisory Committee March 5, 2024 Meeting Announcement - 03/05/2024 | FDA
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: National Center for Immunization & Respiratory Diseases Influenza B/Yamagata Update Lisa Grohskopf, MD, MPH Advisory Committee on Immunization Practices February 28, 2024 •Quadrivalent influenza vaccines introduced in 2013 -14 to provide broader coverage  of influenza B viruses. –Quadrivalents contain one influenza B virus from each lineage (Victoria and Yamagata). –Transition from trivalents to quadrivalents complete by the 2021 -22 influenza season. •No confirmed influenza B/Yamagata viruses…


01 POLIO Brooks 508

Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation use. No rights  are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.Polio Vaccine Work Group
Oliver Brooks, MD, FAAP
ACIP Meeting
February 28, 2024

nOPV2
▪Considerations for the potential use of novel type 2 oral poliovirus
vaccine (nOPV2) as an outbreak control measure in the United States
fIPV
▪Clinical considerations for children who received fractional dose
inactivated polio vaccine ( fIPV) in other countriesPolio Vaccination Work Group Terms of Reference
Policy topics under consideration:

Summary: Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online…


02 POLIO Kidd 508

Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation use. No rights  are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.Considerations for the Potential Use of Novel Type 2 Oral
Poliovirus Vaccine (nOPV2) as an Outbreak Control
Measure in the United States
Sarah Kidd, MD, MPH
ACIP Meeting
February 28, 2024

▪ACIP voting members
–Oliver Brooks (Chair)
–Lynn Bahta
–Sybil Cineas
▪Liaisons
–Lynn Fisher, American Academy of Family Physicians
–Chandy C. John, American Academy of Pediatrics
–Sandra Fryhofer , American Medical Association
–Kathy Kudish, Association of Immunization Managers
–Marcus Plescia , Association of State and Territorial Health Officials
–Paul R. Cieslak , Council of State and Territorial Epidemiologists
–Christine Hahn, Council of State and Territorial Epidemiologists
–Tina Q. Tan, Infectious Diseases Society of America
–Adenike  Shoyinka , Infectious Diseases Society of America
–Mary Wilson, International Society of Travel Medicine
–Jaqueline Lawler, National Association of County and City Health Officials
–Kathy Edwards, Pediatric Infectious Diseases Society
–Joseline Zafack , Public Health Agency of Canada*Polio Work Group Members
*In the event of a Work Group poll, CDC, FDA, and Public Health Agency of Canada members are not included.▪Consultants
–Edwin Asturias
–Doug E Campos -Outcalt *
–Emily Lutterloh
–Jennifer Rosen
–Eli Rosenberg
▪FDA*
–Robin Levis
▪CDC*
–Cara Burns
–Thomas Clark
–Miranda Delahoy
–Brian Edlin
–Concepcion Estivariz
–Halle Getachew
–Sarah Kidd
–Janelle King
–Adriana Lopez
–M. Steve Oberste
▪Poliovirus infection can cause
poliomyelitis and lifelong paralysis
–Paralytic disease occurs in <1% of
infections (varies by serotype)
–Non -paralytic clinical illness occurs in
~25%, including 1% –5% with aseptic
meningitis
–Approximately 75% of infections are
asymptomaticPublic Health Problem

▪Three poliovirus serotypes: type 1, type 2, and type 3
▪Immunity to one serotype does not result in significant
immunity to other serotypes
▪Ratio of paralytic cases to infections varies by serotype
–Type 1: approximately 1/190
–Type 2: approximately 1/1900
–Type 3: approximately 1/1100Poliovirus Serotypes
Nathanson N, Kew OM. Am J Epidemiol 2010;172:1213 –29.

▪Person -to-person spread of poliovirus occurs via the fecal -oral or oral-oral routes
–Fecal -oral is the most important transmission pathway in settings with suboptimal
hygiene and sanitation
▪Patients are most infectious during days immediately before and after onset of
symptoms, but virus may remain present in stool for up to 6 weeks , sometimes
longer
–Individuals with minor symptoms or no illness can shed virusPoliovirus is highly infectious
▪Only polio vaccine used in the US
▪Contains inactivated polioviruses types 1, 2, and 3 polioviruses
▪Induces effective humoral immunity → prevents paralysis
▪Induces some nasopharyngeal mucosal immunity, butlimited
intestinal immunityInactivated Polio Vaccine (IPV)

▪Live attenuated vaccine (Sabin)
–Trivalent OPV ( tOPV ): contains types 1, 2, and 3
–Bivalent OPV ( bOPV ): contains types 1 and 3
–Monovalent OPV ( mOPV #): contains single type (#=1, 2, or 3)
▪Replicates in gut, is shed in stool
▪Induces humoral and mucosal immunity
–Prevents paralysis and transmission ofpoliovirus
▪Historical vaccine of choice for countries with outbreaks
▪Attenuated virus can revert to a neurovirulent form
that causes paralysisOral Polio Vaccine (OPV)

▪Novel, next -generation version of monovalent type 2 oral polio vaccine (nOPV2)
▪Designed to be more genetically stable, less likely to revert to neurovirulent form
▪March 2021 –December 2023:
–Almost 1 billion doses administered in 35 countries under WHO Emergency Use
Listing (EUL) approval
▪December 2023: Earned WHO prequalificationNovel Type 2 Oral Polio Vaccine (nOPV2)
Paralytic polio decreased rapidly in the US after
introduction of polio vaccine
0500010000150002000025000
1950
1952
1954
1956
1958
1960
1962
1964
1966
1968
1970
1972
1974
1976
1978
1980
1982
1984
1986
1988
1990
1992
1994
1996
1998
2000
2002
2004
2006
2008
2010
2012
2014
2016
2018
20201994: Americas
certified polio -free
YearNumber of poliomyelitis cases1955: Salk IPV
1961: Sabin OPV1979: Last indigenous
wild-type case in US
2000: IPV only1997 : Sequential enhanced -potency
          IPV followed by OPV
Global Paralytic WPV1 and cVDPV  Cases1, Previous 12 Months2
https://polioeradication.org/polio -today/polio -now/
WPV1 cases (latest onset)
Pakistan 5 24-Oct-23
Afghanistan 6 04-Sep-23
cVDPV1 cases (latest onset)
DR Congo 90 24-Nov-23
Mozambique 3 06-Nov-23
Madagascar 17 16-Sep-23
cVDPV2 cases (latest onset)
Niger 2 11-Dec-23
Indonesia 3 06-Dec-23
Nigeria 80 03-Dec-23
Zimbabwe 1 02-Dec-23
Guinea 46 28-Nov-23
Chad 49 26-Nov-23
Côte d'Ivoire 6 22-Nov-23
DR Congo 87 19-Nov-23
Yemen 4 17-Nov-23
Tanzania 3 16-Nov-23
Mali 12 06-Nov-23
South Sudan 2 04-Nov-23
Mauritania 1 17-Oct-23
CAR 10 07-Oct-23
Mozambique 1 28-Sep-23
Somalia 4 16-Sep-23
Kenya 8 21-Aug-23
Burundi 1 15-Jun-23
Burkina Faso 2 04-Jun-23
Zambia 1 03-Apr-23
Benin 2 15-Mar-23Data in WHO HQ as of 20 Feb. 20241Excludes viruses detected from environmental surveillance;   2Onset of paralysis: 21 Feb. 2023 to 20 Feb. 2024Endemic country (WPV1)

Paralytic Polio Case in New York State, July 2022
•A case of paralytic polio caused by vaccine -derived poliovirus type 2 (VDPV2) was
confirmed in an unvaccinated young adult from  Rockland County, New York, on
July 21, 2022
•Genetic  sequencing has indicated a linkage to polioviruses collected in
wastewater in Israel, United Kingdom, and Canada
•Rockland County has reported overall low vaccine coverage for over 20 years
•In summer 2022, 60% of children under 2 years of age had received 3 doses of
IPV (zip code level as low as 37%)
•No additional paralytic cases were identified
https://www.health.ny.gov/diseases/communicable/polio/docs/waste_water_surveillance_report.pdf   ▪Poliovirus type 2 genetically linked to the case detected
in wastewater samples in New York (Rockland, Orange,
Sullivan, and Nassau counties and New York City)
▪Retrospective testing detected poliovirus as early as
April 2022
▪Only 2 positive samples since November 1, 2022 (most
recent February 22, 2023)
▪No detections in samples collected in last 11+ months
(since February 2023)Wastewater Testing for Poliovirus in New York

https://www.health.ny.gov/diseases/communicable/polio/docs/waste_water_surveillance_report.pdf
▪2022 New York Strategy: Identify unvaccinated and undervaccinated persons, provide
catch -up vaccination with IPV
▪WHO recommendations for poliovirus outbreaks in countries with exclusive IPV
vaccination and high sanitation and hygiene:
–Conduct a timely outbreak response with IPV only if poliovirus transmission is
confined in a well -defined population group or geographic area.
–If transmission persists, consider an OPV response.
▪Work Group asked to discuss considerations for potential use of nOPV2 as an
outbreak response measure in the USOutbreak Response Vaccination
▪Should nOPV2 be used in combination with a catch -up IPV campaign during a
future type 2 poliovirus outbreak in the US?
–Population: Persons living in area with circulating poliovirus
–Intervention: nOPV2 vaccination for all + catch -up IPV vaccination for un - or under -vaccinated
–Comparison: Catch -up IPV vaccination only
–Outcomes:
•Prevention of paralytic poliomyelitis
•Extent and duration of poliovirus circulation in the community
•Serious adverse effects, including vaccine -associated paralytic polio
•Possible introduction of new vaccine -derived poliovirus type 2Theoretical Policy Question for Work Group
▪Problem
–Is the problem of public health importance?
▪Benefits & Harms
–How substantial are the desirable anticipated effects?
–How substantial are the undesirable anticipated effects?
–Do the desirable effects outweigh the undesirable effects?
–What is the overall certainty of this evidence for the critical outcomes?
▪Values
–Does the target population feel 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?
▪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 on health equity?
▪Feasibility
–Is the intervention feasible to implement?ACIP Evidence to Recommendations ( EtR) Framework
Work group interpretation
Is paralytic poliomyelitis a problem of public health importance?EtR Domain: Public Health Problem
NoProbably
noProbably
yesYes VariesDon’t
know
▪Seroconversion among infants who had received 1 dose of IPV (Sáez -Llorens et al)
–86% 28 days after 1 dose
–98% 28 days after 2 doses
▪Seroconversion among vaccine -naïve infants (Zaman et al; Wilkinson et al)
–46% –64% 28 days after 1 dose
–86% –90% 28 days after 2 dosesEffectiveness:
High Rates of Seroconversion Following nOPV2
Sáez -Llorens et al. Lancet 2021;397:27 –38.
Zaman et al. Lancet 2023;401:131 –39.
Wilkinson et al. Lancet Infect Dis 2023;23:1062 –71.
▪Sabin OPV2 reduces odds of fecal shedding of type 2 virus after a challenge ( Hird  and
Grassly )
▪In small Phase 1 study among adults previously vaccinated with IPV ( Brickley  et al)
•33% had detectable stool neutralization titer against PV2 at 28 days after 1 dose of nOPV2
•15% had detectable PV2 -specific IgA in stool at 28 days after 1 dose of nOPV2Effectiveness: Mucosal Immunity
Hird  and Grassly . PLoS  Pathogens 2012;8(4):e1002599.
Brickley  et al. J Infect Dis 2022;26:287 –91.
Fecal Shedding of nOPV2 Virus After 1st Dose of nOPV2
% of Infants* with Detectable nOPV2 Virus in Stool
Days after 1st dose of nOPV2 Measured by PCR Measured by Culture
7 days 85% 40%
14 days 52% 17%
28 days 40% - 57% 1% - 14%
Zaman et al. Lancet 2023;401:131 –39.
Gast et al. J Infect Dis 2022;226:852 –61.*Includes newborn vaccine -naïve infants and infants who had previously received 3 bOPV  doses and 1 IPV dose
▪nOPV2 more genetically stable than Sabin OPV2, less likely to regain neurovirulence
▪Risk of VAPP in recipients
–nOPV2: estimated 0.07 cases per million recipients (1 per 14.3M recipients)
–Sabin OPV: 0.25 –4 cases per million recipients (1 per 0.25M –4M recipients)
–Risk highest in unimmunized children receiving 1st dose of OPV or in
immunocompromised persons
–Could be mitigated by limiting nOPV2 administration to persons who had
previously received ≥1 IPV doseRisk of Vaccine -Associated Paralytic Polio (VAPP) Following
nOPV2
Bandyopadhyay and Zipursky. Lancet ID 2023;23:e67 –71.
▪>700 million nOPV2 doses administered worldwide in 32 countries since March 2021
–At least  7 separate emergences of new cVDPV2 linked to nOPV2 (cVPDV2 -n)
–At least 61 detected paralytic cases associated with cVDPV2 -n
▪Estimates: nOPV2 is 80% less likely than mOPV2 to seed new cVDPV2
▪Risk of new cVDPV  is highest when campaign coverage is low in a population with
low immunity against poliovirusesRisk of Introducing a New Circulating Vaccine -Derived
Poliovirus ( cVDPV ) Following nOPV2
Davlantes et al. MMWR 2023;72(38):1041 –1042.
https://polioeradication.org/wp -content/uploads/2024/01/GPEI -nOPV2 -Factsheet -20240105.pdf
▪Most recipients will already be fully vaccinated with 3 –4 doses of IPV, already
protected against paralytic disease
▪Anticipated benefits of nOPV2 to recipient
–Higher anti -poliovirus type 2 antibody titer
–Increased odds of mucosal immunity to poliovirus type 2
–For undervaccinated persons: additional protection against paralytic disease
–For previously vaccinated persons: unlikely clinical benefit
▪Potential harms of nOPV2 to recipient
–Extremely low, but non -zero risk of VAPP (<1 case per 14.3 million doses administered)
–Risk of chronic infection if given to child with unrecognized immunocompromiseFor Individual nOPV2 Recipients
Potential effects of adding nOPV2 to the IPV outbreak response
▪Potential benefits to population
–Decreased transmission among nOPV2 recipients → outbreak ends earlier → fewer paralytic cases
–Passive vaccination of unvaccinated → decreased transmission and fewer paralytic cases
▪Potential harms to population
–Passive vaccination of unvaccinated → risk of VAPP among unvaccinated
–Possible ongoing transmission of nOPV2 virus → new cVDPV2 -n
–Possible chronic infection in immunocompromised
▪Magnitude of benefits and harms depends on nOPV2 coverage, extent of mixing
between nOPV2 recipients and unvaccinated (and immunocompromised)At the Population Level
Potential effects of adding nOPV2 to the IPV outbreak response
Modeling:
Expected Paralytic Cases Under Different Mixing Scenarios
for a cVDPV2 Outbreak Similar to 2022 New York Outbreak
Thompson et al. Vaccine 2024;42:819 –27.
Note: Model assumed the number of vaccine doses administered was same as number of IPV doses administered
during 2022 New York outbreak.Modeled cVDPV2 cases
Vaccine used for outbreak response IPV None mOPV2 nOPV2 best nOPV2 worst
Subpopulation isolation 0.88 1.89 0.64 0.55 0.67
No isolation 0.64 0.86 0.51 0.44 0.53
Partial isolation 0.35 0.39 0.30 0.27 0.31
Modeling:
Expected Paralytic Cases Under Different Mixing Scenarios
for cVDPV1 Outbreak and Hypothetical Novel Type 1 OPV
Thompson et al. Vaccine 2024;42:819 –27.
Modeled cVDPV1 cases
Vaccine used for outbreak response IPV None mOPV1 nOPV1 best nOPV1 worst
Subpopulation isolation 56 65 45 22 47
No isolation 130 179 91 26 97
Partial isolation 36 163 23 11 25
Note: Model assumed the number of vaccine doses administered was same as number of IPV doses administered
during 2022 New York outbreak.
Minimal Small Moderate Large VariesDon’t
knowEtR Domain: Benefits & Harms
Work group interpretation
How substantial are the desirable  anticipated effects of nOPV2* on the
individual and population levels?
*during a VDPV2 outbreak, when nOPV2 given in addition to any IPV doses received as part of routine immunization
Minimal Small Moderate Large VariesDon’t
knowEtR Domain: Benefits & Harms
Work group interpretation
How substantial are the undesirable  anticipated effects of nOPV2* on
the individual and population levels?
*during a VDPV2 outbreak, when nOPV2 given in addition to any IPV doses received as part of routine immunization
Yes, favors
nOPV2No, favors IPV
onlyFavors either
option equallyVaries Don’t knowEtR Domain: Benefits & Harms
Work group interpretation
Do the desirable effects of nOPV2* outweigh the undesirable effects on
the individual and population levels?
*during a VDPV2 outbreak, when nOPV2 given in addition to any IPV doses received as part of routine immunization
▪Expanded access investigational new drug application (EA -IND)
▪Requires application to FDA and FDA authorization
▪If implemented, nOPV2 EA -IND program must include
–Signed informed consent by vaccinees and/or guardians
–System for monitoring vaccine safety
–Enhanced surveillance for possible VAPP cases
–Environmental surveillance for new cVDPV2s
–System for tracking and accounting for every dose for containment purposesImplementing an nOPV2 Program in the US
NoProbably
noProbably
yesYes VariesDon’t
knowEtR Domain: Resource Use
Work group interpretation
Is an nOPV2 campaign* a reasonable and efficient allocation of
resources?
*during a VDPV2 outbreak, when nOPV2 given in addition to any IPV doses received as part of routine immunization
NoProbably
noProbably
yesYes VariesDon’t
knowEtR Domain: Feasibility
Work group interpretation
Is a nOPV2 campaign* feasible to implement?
*during a VDPV2 outbreak, when nOPV2 given in addition to any IPV doses received as part of routine immunization
▪Trivalent OPV ( tOPV ) was removed from vaccination schedule in 2000 and replaced with IPV because
any risk of VAPP was deemed unacceptable; this might be barrier to acceptance of a new OPV vaccine
▪The need for signed informed consent will likely be a deterrent
▪Unclear whether general public will accept an OPV if they are already protected from paralytic
infection by IPV
▪Unclear whether population most at risk (those with low childhood vaccination coverage and high
rates of vaccine skepticism) will accept an OPV vaccine
▪Perceptions of risk and vaccine acceptance might shift in outbreak setting, if there is >1 paralytic case
in a communityValues and Acceptability Considerations
NoProbably
noProbably
yesYes VariesDon’t
knowEtR Domain: Values of Target Population
Work group interpretation
Does the target population feel that the desirable effects of nOPV2* are
large relative to undesirable effects?
*during a VDPV2 outbreak, when nOPV2 given in addition to any IPV doses received as part of routine immunization
Important
uncertainty
or variabilityProbably
important
uncertainty
or variabilityProbably not
important
uncertainty
or variabilityNo
important
uncertainty
or variabilityNo known
undesirable
outcomesEtR Domain: Values of Target Population
Work group interpretation
Is there important uncertainty or variability in how much people value
the main outcomes?
NoProbably
noProbably
yesYes VariesDon’t
knowEtR Domain: Acceptability to Key Stakeholders
Work group interpretation
Is nOPV2* acceptable to key stakeholders?
*during a VDPV2 outbreak, when nOPV2 given in addition to any IPV doses received as part of routine immunization
Globally
▪Single manufacturer ( BioFarma , Indonesia)
▪Managed via a global stockpile
▪Supply shortages have occurred in the past
▪In US, IPV is readily available, provides protection against paralysis from cVDPV2
▪In many countries with cVDPV2 outbreaks, limited protection against cVDPV2 unless
there are nOPV2 or mOPV2 campaigns
In US
▪Preventing transmission protects unvaccinated/undervaccinated and
immunocompromisedEquity Considerations
Reduced
equityProbably
reduced
equityProbably
no impactProbably
increased
equityIncreased
equityVariesDon’t
knowEtR Domain: Equity
Work group interpretation
What would be the impact of an nOPV2 campaign* in the US on health
equity?
*during a VDPV2 outbreak, when nOPV2 given in addition to any IPV doses received as part of routine immunization
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
consequencesWork Group Judgement: Balance of Consequences
Using nOPV2 as an outbreak control measure in the US*
*during a VDPV2 outbreak, when nOPV2 given in addition to any IPV doses received as part of routine immunization
▪At this time, the work group believes the undesirable consequences probably
outweigh OR are closely balanced with the desirable consequences.
▪Main considerations included
–IPV is readily available in the US and protects against paralytic disease
–Primary benefit of adding nOPV2 to an outbreak response would be to reduce transmission of outbreak virus,
reduce risk of paralytic disease in undervaccinated or immunocompromised persons
–Differences of opinion regarding the value of reducing asymptomatic  transmission or ending asymptomatic
transmission earlier during outbreak
–Extremely low, but non -zero risk of VAPP (est. 1 per 14.3 million recipients) or new cVDPV2
–Uncertainty about public and stakeholder acceptance of nOPV2
▪Balance of undesirable consequences vs. desirable consequences might shift in the
future depending on size and scope of outbreakSummary
Use of nOPV2 During a cVDPV2 Outbreak in the US
Questions and Discussion


Pneumococcal 06 Kobayashi 508

Pneumococcal Vaccines Work Group Considerations and
Next Steps
Miwako Kobayashi, MD, MPH
Pneumococcal Vaccines Work Group
Advisory Committee on Immunization Practices
February 22, 2023

         Proposed Policy Questions
 Should PCV20 be recommended as an option for pneumococcal
conjugate vaccination according to currently recommended dosing and schedules, for U.S. children aged <2 years?
 Should PCV20 without PPSV23 be recommended as an option for pneumococcal vaccination for U.S. children aged 2–18 years with underlying medical conditions that increase the risk of pneumococcal disease?

       Additional Considerations
 Cost-effectiveness analysis will be performed to assess:
• Incremental benefit of PPSV23 use in addition to PCV20 in children
aged 2–18 years with underlying medical conditions.
• Incremental benefit of PCV20 use in children who completed the
recommended PCV series with either PCV13 or PCV15.
Pneumococcal  Disease  Risk in Children  with  Underlying  Medical
Conditions
Asthma,  Chronic  Kidney  Disease,  Chronic  Liver  Disease

 Are childre  n wit  h chroni  c kidne  y disease o  f an  y stag  e a t increase  d risk
o f pneumococca  l disease? Specific Questions Being Considered by the Work
Group
•
•
•  Are  children  with  chroni  c live  r diseas  e a t increase  d risk  o f pneumococcal
disease? Are  children  with  asthma  at  increased  risk  of  pneumococcal  disease
regardless  o f high-dose  oral  corticosteroid  use?

       Differences in the Indications for Children vs Adults
with Asthma
• Pediatric recommendation1,2:
• Including asthma if treated with high-dose oral
corticosteroid therapy
• Adult recommendation3,4:
• Includes chronic obstructive pulmonary disease,
emphysema, and asthma
1. Nuorti et al. MMWR RR 2010
2. Kobayashi et al. MMWR 2022. 71(37); 1174–1181
3. Matanock et al. MMWR 2019
4. Kobayashi et al. MMWR 2022. 71(4); 109–117
Risk-Based Pneumococcal Vaccine Recommendations

  Diabetes mellitus
Cerebrospinal fluid leak Cochlear implant Chronic renal failure or nephrotic syndrome Congenital or acquired asplenia, or splenic
dysfunction
Congenital or acquired immunodeficiency
Diseases and conditions treated with
immunosuppressive drugs or radiation therapy
HIV infection
Sickle cell disease or other hemoglobinopathies
Solid organ transplant
Should we add “chronic liver disease” as part of pediatric
risk-based recommendation? Children Adults
Alcoholism
C
hronic heart disease
Ch
ronic lung disease
Chronic liver disease
Cigarette smoking
Risk-Based Pneumococcal Vaccine Recommendations
Children Adults
Alcoholism
Chronic heart disease
Chronic lung disease Chronic liver disease Cigarette smoking

    Diabetes mellitus
Cerebrospinal fluid leak Cochlear implant
or nephrotic syndrome
Chronic renal failure
Congenital or acquired asplenia, or splenic
dysfunction
Congenital or acquired immunodeficiency
Diseases and conditions treated with
immunosuppressive drugs or radiation therapy
HIV infection
Sickle cell disease or other hemoglobinopathies
Solid organ transplant The intent has been to provide additional protection for
those on dialysis or about to be on dialysis
 Should the risk-based recommendations be expanded to
all CKD stages?
Work  Group  Next  Steps

             Work Group Next Steps
• Review of evidence and Work Group interpretation of remaining EtR domains
(Values, Acceptability, Resource Use, Feasibility )
• Review findings from cost-effectiveness analyses (CDC and other groups)
• Draft policy options on PCV20 use in U.S. children for consideration by the committee

       Questions for the Committee
• Does the Committee agree with the policy questions being
considered by the Work Group?
• Are there additional data the Committee would like to see before deciding on policy options for a vote?

         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: Pneumococcal Vaccines Work Group Considerations and  Next Steps  Miwako Kobayashi, MD, MPH  Pneumococcal Vaccines Work Group  Advisory Committee on Immunization Practices  February 22, 2023                                                            Proposed Policy Questions   Should PCV20 be recommended as an option for pneumococcal  conjugate vaccination according to currently recommended dosing and schedules, for U.S. children aged <2 years?   Should PCV20 without PPSV23 be recommended as…


Mening 01 Poehling 508

National Center for Immunization & Respiratory Diseases
ACIP Meningococcal Vaccines Work Group
Introduction
Katherine Poehling, MD, MPH
Work Group Chair
February 23, 2023

  Meningococcal Vaccines Work Group
 ACIP Members
– Kat
herine Poehling (Chair)
– Lynn Bahta
– Jam
ie Loehr
 Ex Officio Members
– Mar
garet Bash (FDA)
– Mark Connelly (FDA)
– Fra
ncisco Leyva (NIH)
 CDC Lead
– Sam Crowe (DBD/NCIRD)
 Liaisons and Consultants
– A
mra Resic (AAFP)
– Samir Shah (AAP)
– Sharon McMullen (ACHA)
– Cacky Tate (AIM)
– Paul Cieslak (CSTE)
– Jeff Goad (NFID)
– Jessica Cataldi (PIDS)
– Amy Middleman (SAHM) – David Stephens (Emory)
 CDC Contributors
– L
eAnne Fox (DBD/NCIRD)
– Susan Hariri (DBD/NCIRD)
– Lucy McNamara (DBD/NCIRD)
– Alison Albert (DBD/NCIRD)
– Noele Nelson (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
– D
oug Campos-Outcalt (Arizona)
– Rebecca Morgan (McMaster)
2

 October ACIP Meeting Recap
 Menveo one-vial presentation

 Introduction to the two new MenABCWY vaccines
–
 Manufacturers: GSK and Pfizer
– Policy questions
– PICOs
– Next steps
3

    Work Group Schedule Updates
Task 2022 2023 2024
6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 6
Menveo Solution
Pfizer Pentavalent Vaccine
GSK Pentavalent Vaccine
4

  Proposed Timeline of ACIP Presentations
February
2023 June
2023 October
2023
• Epidemiology of • Pfizer GRADE, EtR, • Pfizer vote
meningococcal and cost study
• GS
K GRADE, EtR, di
sease
• GS
K trial data and cost study
• Pf
izer trial data
5

      Summary of Recent Work Group Activities
 GSK and Pfizer presented on their pentavalent vaccines and work group
asked clarifying questions
 Work group discussed whether to reconsider adolescent immunization schedule
 Decided to postpone any reviews of the schedule until after both pentavalent vaccines have been assessed
– Vaccine reviews will be complex and challenging
– Need to understand epidemiology of meningococcal disease after COVID-19
6

  Agenda for Today
 Epidemiology of Meningococcal Disease in the United States
–
 A
my Rubis, CDC

 Pfizer’s MenABCWY Vaccine Clinical Trials Data
–
 P
fizer Representative

 Work Group Interpretation of Pfizer’s MenABCWY Vaccine Clinical Trials Data
–
 Sam Crowe, CDC
7

   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: National Center for Immunization & Respiratory Diseases  ACIP Meningococcal Vaccines Work Group  Introduction  Katherine Poehling, MD, MPH  Work Group Chair  February 23, 2023                                                                                Meningococcal Vaccines Work Group   ACIP Members  – Kat herine Poehling (Chair)  – Lynn Bahta  – Jam ie Loehr   Ex Officio Members  – Mar garet Bash (FDA)  – Mark Connelly (FDA)  – Fra ncisco Leyva (NIH)   CDC Lead  – Sam…


Mening 02 Rubis 508

National Center for Immunization & Respiratory Diseases
Epidemiology of Meningococcal Disease in the
United States
Amy Rubis, MPH
Advisory Committee on Immunization Practices Meeting
February 23, 2023

  Agenda
 Overall epidemiology of meningococcal disease in the
United States
 Recent notable epidemiology
– C
iprofloxacin- and penicillin-resistant serogroup Y
meningococcal disease cases
– Outbreaks
2

 Meningococcal Disease Surveillance
 Cases reported through National Notifiable Diseases
Surveillance System (NNDSS)

 Additional serogroup, outcome, and clinical characteristics collected nationally through Enhanced Meningococcal Disease Surveillance (EMDS)
–
 Isolates submitted for whole genome sequencing
3

   Meningococcal Disease Surveillance Data, 2020–2022
 2020 data are final
 Delays in obtaining and finalizing surveillance data for 20
21
an
d 20
22
– Ser
ogroup missing for 17% of cases
– Clinical characteristics not yet complete for 20
22
– Al
l available isolates not yet received and tested to confirm
serogroup and antimicrobial susceptibility
4

 Meningococcal Disease Incidence –
United States, 1996–2019 1.2 cases/100,000
population Incidence per 100,000 1.40
1.20
1.00 0.80 0.60
0.40
0.20
0.11 cases/100,000
population MenACWY vaccine
MenB vaccine
0.00
1996 2000 2005 2010 2015 2019
Year
Abbreviations: MenACWY vaccine = quadrivalent conjugate meningococcal vaccine against serogroups A, C, W, Y; MenB vaccine = serogroup B meningococcal vaccine
Source: 1996–2019 NNDSS Data
5

 Meningococcal Disease Incidence –
United States, 1996–2021* 1.2 cases/100,000
population Incidence per 100,000 1.40
1.20
1.00 0.80 0.60
0.40
0.20
0.06 cases/100,000
population MenACWY vaccine
MenB vaccine
0.00
1996 2000 2005 2010 2015 2021
Year
Abbreviations: MenACWY vaccine = quadrivalent conjugate meningococcal vaccine against serogroups A, C, W, Y; MenB vaccine = serogroup B meningococcal vaccine
Source: 1996–2021 NNDSS Data. *2021 NNDSS data are preliminary. 6

 Meningococcal Disease Incidence –
United States, 1996–2022* 1.2 cases/100,000
population Incidence per 100,000 1.40
1.20
1.00 0.80 0.60
0.40
0.20
0.09 cases/100,000
population MenACWY vaccine
MenB vaccine
0.00
1996 2000 2005 2010 2015 2020 2022
Year
Abbreviations: MenACWY vaccine = quadrivalent conjugate meningococcal vaccine against serogroups A, C, W, Y; MenB vaccine = serogroup B meningococcal vaccine
Source: 1996–2022 NNDSS Data. *2021–2022 NNDSS data are preliminary. 7

     Trends in Meningococcal Disease Incidence by
Serogroup – United States, 2006–2022* Incidence per 100,000 0.12
B C Y W Other
0.1
0.08
0.06
0.04
0.02
0
2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022
Year
Source: NNDSS data with additional serogroup data from Active Bacterial Core surveillance (ABCs) and state health departments
*2021 and 2022 data are preliminary
8

 0 0.2 0.4 0.6 0.8 1 1.2 1.4 Incidence per 100,000 B ACWY Oth/Unk Average Annual Meningococcal Disease Incidence by
Age-Group and Serogroup―United States, 2010–2019
<1 year 1 year 2-4 years 5-10 11-15 16-20 21-25 26-44 45-64 65-84 85+
years years years years years years years years
A
ge Group
Source: NNDSS data with additional serogroup data from ABCs and state health departments
 9
Average Annual Meningococcal Disease Incidence by
Age-Group and Serogroup―United States, 2020–2022*
1.4
B ACWY Oth/Unk
1.2
1
0.8
0.6 0.4 0.2
0
<1 year 1 year 2-4 5-10 11-15 16-20 21-25 26-44 45-64 65-84 85+
years years years years years years years years years

 Age Group
Source: NNDSS data with additional serogroup data from ABCs and state health departments
*2021 and 2022 data are preliminary
Incidence per 100,000
10

    Recent Meningococcal Disease Cases
 Historically resistance in N. meningitidis was rare
 Ciprofloxacin- and penicillin-resistant serogroup Y cases
detected in 2020
– 27 cases from 2019–2022
– 7
8% among Hispanic or Latino persons
– Age range <1–97 years, mean 31, median 23
• Only 1 case 11–20 years of age
– No cases in vaccinated individuals
11

Resistant Serogroup Y Meningococcal Disease
Cases―United States, 2013–2022
Data are not final and
0 0.02 0.04 0.06 0.08 0.1 0.12 0.14 0.16 0.18 0.2
0 5 10 15 20 25
Incidence per 100,000 Number of cases numbers may increase
2013 2014 2015 2016 2017 2018 2019 2020 2021 2022
β-lactamase-positive only Dual-resistant Meningococcal Disease Incidence
*2021 and 2022 data are preliminary 12

       Recent Meningococcal Disease Outbreaks
 Largest outbreak predominantly in men who have sex with
men (MSM) reported to date
– January 2022–present*
– 4
3 serogroup C cases, 9 deaths (21% CFR)
– 12/43 non-MSM (5 women) in outbreak
– 15 (35%) cases in people living with HIV
– Age range 20–77 years, mean 35, median 31
13
*The outbreak is ongoing. Case counts may change.

       Recent Meningococcal Disease Outbreaks
 Unusually lethal strain of serogroup Y
– June 2022–present*
– 11 cases, 3 deaths (27% CFR)
–
 10/11 cases in Black or African American persons
– Age range 30–78 years, mean 46, median 39
– Sequence type 1466, clonal complex 174
14
*The outbreak is ongoing. Case counts may change.

    Recent Meningococcal Disease Outbreaks
 People experiencing homelessness
– 2021
• 1 out
break of 3 serogroup C cases
• Age
range 22–37 years
– 2022
• 1 ou
tbreak of 2 serogroup C cases at the same shelter
• Ag
es: 37 and 41 years
15

        Conclusions
 Incidence of meningococcal disease declined during 2020–
2021, but increased in 2022
 New strains emerging in the US
– Pr
edominantly affecting racial and ethnic minority groups
– Unclear how this will change overall epidemiology
 More complete 2021 and 2022 data are needed
 More years of data needed to understand post-COVID-19
ep
idemiology
16

    Thank You
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: National Center for Immunization & Respiratory Diseases  Epidemiology of Meningococcal Disease in the  United States  Amy Rubis, MPH  Advisory Committee on Immunization Practices Meeting  February 23, 2023                      Agenda   Overall epidemiology of meningococcal disease in the  United States   Recent notable epidemiology  – C iprofloxacin- and penicillin-resistant serogroup Y  meningococcal disease cases  – Outbreaks  2                      Meningococcal Disease Surveillance  …


Mening 03 Maguire 508

1 Pfizer ConfidentialMenABCWY
Meningococcal  Vaccine
Jason D. Maguire, MD, MPH
Clinical Lead, Phase 3 Program
Pfizer Vaccines Clinical R&D
2 Pfizer Confidential
For Internal and Restricted Pfizer Use Only –Not for Distribution. Privileged and Confidential.MenABCWY vaccine composition
Confidential•MenABCWY vaccine is composed of drug substance from:
–Trumenba®(MenB-fHbp): licensed in the US for the prevention of invasive disease caused by Neisseria meningitidis group
B in individuals 10 through 25 years of age
–Nimenrix® (MenACWY- TT): licensed ex -US for the prevention of invasive disease caused by Neisseria meningitidis
serogroups A, C, W, and Y in individuals 6 weeks of age and older. •Active immunization of individuals 10 through 25 years of age against invasive meningococcal diseases
caused by Neisseria meningitidis serogroups A, B, C, W, Y
•Dosing:
–Administer two doses at least 6 months apart for prevention of meningococcal disease caused by serogroups A, B, C, W
and Y .
–Administer one dose for prevention of meningococcal disease caused by serogroups A, C, W and Y .
–A booster dose may be administered to individuals who have previously completed a primary series with MenABCWY or
MenB-fHbp vaccine or who have previously received MenACWY conjugated vaccinesIndication and dosing being sought for MenABCWY vaccineMenABCWY Vaccine Overview
3 Pfizer ConfidentialAdolescent meningococcal vaccination platform options for MenABCWY
vaccine
11-12 years 16-23 years
B B ACWY ACWY
ABCWY ABCWY ABCWY
ABCWY ABCWY ABCWY
Study Population 10- 25 years (ACWY -naïve and primed)Current Vaccine
Recommendation
MenABCWY
vaccine options
MenABCWY
vaccine clinical
data
0, 6-12 monthsACWY
protectionABCWY
pr
otectionBooster dos e (4 years)
for ABCWY protection
4 Pfizer ConfidentialMenABCWY vaccine clinical program overview
Blood vial image source: Flaticon.com•ABCWY responses after 2
doses (0,6m)
•ACWY responses after 1 doseKey immunogenicity ( hSBA) data to
be discussed
•ABCWY responses after 2 doses (0,12m)
•ABCWY 4 -year persistence
and booster response
•All participants were meningococcal serogroup B vaccine naïve prior to study entry
•80% of participants in the Phase 3 study were Caucasian; 10% black and African Americans; 25% of participants being Hispanic or Latino
5 Pfizer Confidential Breakthroughs that change patients’ livesImmunogenicity
6 Pfizer ConfidentialImmunogenicity objectives and endpoints
Abbreviations: hSBA=human serum bactericidal assay; GMT=geometric mean titer ;MenB =serogroup B
*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. †hSBA titer ≥1:8 (1:16 for A22) for all 4 primary strains 1 month after Dose 2.MenB immunogenicity analysis: Same approach taken as for Trumenba licensure in the US
•4 MenB test strains utilized, 2 from Factor H Binding Protein ( fHbp ) subfamily A (A22, A56) and 2 from subfamily B (B24, B44)
•hSBA results provide information on breadth of coverage against MenB strains
•All strains express vaccine -heterologous fHbp variants
•Strains and fHbp variants expressed are representative of known genetic diversity; strains were randomly selected
•hSBA seropositivity defined as titers ≥1:8 or ≥1:16, which is greater than the 1:4 correlate of protectionFDA agreement for licensure
ACWY evaluation
(non-inferiority after 1 and 2
doses of MenABCWY vaccine
versus MenACWY -CRM)B ev aluation
(non
-inferiority after 2 doses of
MenABCWY vaccine versus
MenB -fHbp)A BCWY evaluation
(O
ther endpoints)
•h
SBA seroresponse* (4 - fold)
•Naïve and primed participants•hSBA seroresponse* (4 - fold)
•Composite response†•hSBA thresholds (1:4, 1:8, 1:16)
•G
MTs
7 Pfizer ConfidentialImmunogenicity
ACWY-naive
8 Pfizer Confidential
A single dose of MenABCWY vaccine can be used as an alternative to
ACWY vaccines in ACWY-naïve adolescentsStudy C3511001 | Evaluable Immunogenicity Population
Percentage of participants achieving hSBA seroresponse*1 month after
vaccination for serogroups
0102030405060708090100
A C W Y%ACWY
Abbreviations: hSBA=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, seroresponse is a titer ≥4 times the 1:8. For those with a baseline hSBA
titer ≥1:8, seroresponse is a titer ≥4 times the baseline titer.
N=492- 501 for MenABCWY group; N=244- 254 for MenB -fHbp + MenACWY -CRM group.
Data on File, Study C3511001 (NCT04440163) Aug 2022, Pfizer Inc.MenABCWY MenB -fHbp + MenACWY -CRM
•1 dose of MenABCWY vaccine was noninferior to 1 dose of MenACWY -CRM in ACWY -naïve participants
•82.4% -99.4% of participants had serogroups ACWY hSBA titers ≥1:8 after 1 dose of MenABCWY vaccineComparisons (ACWY -naïve participants):
•MenABCWY vaccine 1 month after first dose
•MenACWY -CRM 1 month after single dose
9 Pfizer Confidential0102030405060708090100
A C W Y%Percentage of participants achieving hSBA seroresponse*1 month after
vaccination for serogroups ACWY
MenABCWY MenB -fHbp + MenACWY -CRM2 doses of MenABCWY vaccine elicit higher responses versus a single
dose of MenACWY-CRM in ACWY -naïve participants
Abbreviations: hSBA=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, seroresponse is a titer ≥4 times the 1:8. For those with a baseline hSBA
titer ≥1:8, seroresponse is a titer ≥4 times the baseline titer.
N=439- 451 or MenABCWY group; N=244- 254 for MenB -fHbp + MenACWY -CRM group.
Data on File, Study C3511001 (NCT04440163) Aug 2022, Pfizer Inc.Study C3511001 | Evaluable Immunogenicity Population
•2 doses of MenABCWY vaccine were noninferior to 1 dose of MenACWY -CRM in ACWY -naïve participants
•99.1-99.8% of participants had serogroups ACWY hSBA titers ≥1:8 after 2 doses of MenABCWY vaccine
Comparisons (ACWY -naïve participants):
•MenABCWY vaccine 1 month after second dose
•MenACWY -CRM 1 month after single dose
10 Pfizer Confidential0102030405060708090100
A22 A56 B24 B44 Composite%
MenABCWY MenB -fHbp + MenACWY -CRMresponse†1 month after vaccination for serogroup B Percentage of participants achieving hSBA seroresponse*and composite Study C3511001 | Evaluable Immunogenicity Population
Abbreviations: hSBA=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. †hSBA titer ≥1:8 (≥1:16 for A22) for all 4 MenB strains 1 month after Dose 2. ^≥1:16 for A22 strain
N=755- 845 for MenABCWY group; N=383- 419 for MenB -fHbp + MenACWY -CRM group.
Data on File, Study C3511001 (NCT04440163) Aug 2022, Pfizer Inc.•2 doses of MenABCWY vaccine were noninferior to 2 doses of MenB -fHbp
•83.4-98.7% of participants had serogroup B hSBA titers ≥1:8^after 2 doses of MenABCWY vaccine2 doses of MenABCWY vaccine elicit higher responses versus 2 doses of
MenB -fHbp in B-naïve participants
Comparisons  (B -naïve participants):
•MenABCWY vaccine 1 month after second dose
•MenB -fHbp 1 month after second dose

11 Pfizer ConfidentialMenABCWY vaccine protects against all 5 serogroups with 2 doses given 6
to 12 months apart
Seroresponse* 1m PD2MenABCWY 0, 6m
(Study 1001)MenABCWY 0, 12m
(Study 1004)
Serogroups N^ % 95% CI N^ % 95% CI
A 447 97.8 95.9, 98.9 116 99.1 95.3, 100
C 451 93.3 90.6, 95.5 115 99.1 95.3, 100
W 439 97.3 95.3, 98.6 113 99.1 95.2, 100
Y 446 94.4 91.8, 96.3 111 98.2 93.6, 99.8
MenB strain
A22 778 83.0 80.2, 85.6 111 95.5 89.8, 98.5
A56 807 95.9 94.3, 97.2 115 100 96.8, 100
B24 833 68.1 64.8, 71.2 113 92.9 86.5, 96.9
B44 845 86.5 84.0, 88.7 116 94.8 89.1, 98.1
MenB composite hSBA response†
Before Dose 1 812 1.2 0.6, 2.3 114 0.9 0.0, 4.8
1 Month after Dose 2 755 78.3 75.2, 81.2 110 96.4 91.0, 99.0Study C3511001, Evaluable Immunogenicity Population │ Study C3511004, Evaluable Immunogenicity Population
Abbreviations: hSBA=serum bactericidal assay using human complement; MenB =serogroup B.
*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.  ^ Number of subjects with valid and determinate hSBA titer for the given
strain; for study 1001, population includes ACWY -naïve participants for serogroups ACWY.†hSBA titer ≥ 1:8 (1:16 for A22) for all 4 MenB strains 1 month after Dose 2.
Data on File, Study C3511001 (NCT04440163) and C3511004 (NCT04440176) Aug 2022, Pfizer Inc.•2 doses of MenABCWY vaccine given 12 months apart elicit higher serogroup B responses
•98.3-100% of participants had serogroups ABCWY hSBA titers ≥1:8 following 2 doses of MenABCWY
vaccine given 12 months apart
12 Pfizer ConfidentialMenACWY seroprotection persists up to 4 years in ACWY -naïve participantsStudy B1971057 | mITT and Booster Evaluable Immunogenicity Populations
Percentage of individuals* with hSBA titers ≥ 1:8 at all timepoints
A
WC
Y020406080100
Baseline 1m PD2 12m PD2 24m PD2 36m PD2 48m PD2Percentage (%)
020406080100
Baseline 1m PD2 12m PD2 24m PD2 36m PD2 48m PD2
020406080100
Baseline 1m PD2 12m PD2 24m PD2 36m PD2 48m PD2Percentage (%)020406080100
Baseline 1m PD2 12m PD2 24m PD2 36m PD2 48m PD2Baseline           7m PD1         18m PD1       30m PD1         42m PD1        54m PD1
Baseline          7m PD1        18m PD1        30m PD1        42m PD1        54m PD1Baseline        7m PD1       18m PD1        30m PD1      42m PD1      54m PD1
Baseline         7m PD1       18m PD1       30m PD1       42m PD1       54m PD1
MenABCWY MenB -fHbp + MenACWY -CRM
Abbreviations: hSBA=serum bactericidal assay using human complement; PB=post booster; PD1=post dose 1; PD2=post dose 2.
*Number of subjects with valid and determinate hSBA titer for the given strain ranged from 95- 112 for MenABCWY and 54- 64 for MenB -fHbp + MenACWY -CRM (Stage 2 mITT population [baseline through
36m PD2/42m PD1]), and 59- 60 for MenABCWY and 36- 37 for MenB -fHbp + MenACWY -CRM (Booster evaluable immunogenicity population [48m PD2 /54m PD1 Post Primary and Post Booster]).
Data on File, Study B1971057 (NCT03135834) Aug 2022, Pfizer Inc.
13 Pfizer ConfidentialStudy B1971057 | Booster Evaluable Immunogenicity Population
Booster response observed following a dose of MenABCWY vaccine 4
years after a 2 dose primary series (0,6m) in ACWY -naïve participants
100% of participants had ACWY hSBA titers ≥1:8 following a booster dose of MenABCWY vaccine at 4 years
Abbreviations: hSBA=serum bactericidal assay using human complement; GMT= geometric mean titer; Post primary series =2 doses for MenABCWY and a single dose for MenACWY -CRM.
*Number of subjects with valid and determinate hSBA titer for the given strain ranged from 59- 60 for MenABCWY and 35- 37 for MenB -fHbp + MenACWY -CRM. ^Pre booster= 4 years after
second dose of MenABCWY and 4.5 years after single dose of MenACWY -CRM.
Data on File, Study B1971057 (NCT03135834) Aug 2022, Pfizer Inc.
Comparisons (ACWY -naïve participants):
•MenABCWY vaccine 4 years^ after second dose (pre booster) and 1 month after
booster
•MenACWY -CRM 4.5 years^ after single dose (pre booster) and 1 month after
boosterA C W Y
248163264128256512102420484096
Post
primaryPre^ Post Post
primaryPre^ Post Post
primaryPre^ Post Post
primaryPre^ PostGMTGMTs* 4 years after primary vaccination and 1 month after booster for
serogroups ACWY
booster booster booster booster
MenABCWY MenB -fHbp + MenACWY -CRM
14 Pfizer Confidential020406080100
Baseline 1m PD2 12m PD2 24m PD2 36m PD2 48m PD2Percentage (%)A22†
B24A56
B44020406080100
Baseline 1m PD2 12m PD2 24m PD2 36m PD2 48m PD2Percentage (%)
020406080100
Baseline 1m PD2 12m PD2 24m PD2 36m PD2 48m PD2
020406080100
Baseline 1m PD2 12m PD2 24m PD2 36m PD2 48m PD2
MenABCWY MenB -fHbp + MenACWY -CRMMenB seroprotection up to 4 years after 2 doses of MenABCWYStudy B1971057  | mITT and Booster Evaluable Immunogenicity Populations
Percentage of individuals* with hSBA titers ≥ 1:8†at all timepoints
Abbreviations: hSBA=serum bactericidal assay using human complement; PD2=post dose 2.
*Number of subjects with valid and determinate hSBA titer for the given strain ranged from 162- 212 for MenABCWY and 83- 137 for MenB -fHbp + MenACWY -CRM (Stage 2 mITT population [baseline through
36m PD2]), and 121- 129 for MenABCWY and 81- 87 for MenB -fHbp + MenACWY -CRM (Booster evaluable immunogenicity population [48m PD2 Post Primary and Post Booster]).†hSBA ≥1:16 for A22.
Data on File, Study B1971057 (NCT03135834) Aug 2022, Pfizer Inc.
15 Pfizer ConfidentialStudy B1971057 | Booster Evaluable Immunogenicity Population
A22 A56 B24serogroup B
B441024
512
256128
64MT G
3216
84
2
Post Pre Post Post Pre Post Post Pre Post Post Pre Post
primary booster primary booster primary booster primary booster
MenABCWY MenB -fHbp + MenACWY -CRMGMTs* 4 years after primary vaccination and 1 month after booster for
•95.1-100% of participants had B hSBA titers ≥1:8^ following a booster dose of MenABCWY vaccine 4 years
Abbreviations: hSBA=serum bactericidal assay using human complement; GMT= geometric mean tier; Post primary series (2 doses for both MenABCWY and MenB -fHbp )
*Number of subjects with valid and determinate hSBA titer for the given strain ranged from 121- 130 for MenABCWY and 81- 88 for MenB -fHbp + MenACWY -CRM. ^≥1:16 for A22 strain
Data on File, Study B1971057 (NCT03135834) Aug 2022, Pfizer Inc.Comparisons (B -naïve participants):
•MenABCWY vaccine 4 years after second dose (pre booster) and 1
month after booster
•MenB -fHbp 4 years after second dose (pre booster) and 1 month after
booster
Booster response observed following a dose of MenABCWY vaccine 4
years after a 2 dose primary series (0,6m) in B-naïve participants
16 Pfizer ConfidentialImmunogenicity
ACWY-primed
17 Pfizer Confidential0102030405060708090100
A C W Y(%)Percentage of participants achieving hSBA seroresponse*1 month after
vaccination for serogroups ACWY
MenABCWY MenB -fHbp + MenACWY -CRM
•1 dose of MenABCWY vaccine was noninferior to 1 dose of MenACWY -CRM in ACWY -primed participants
•99.5-100% of participants had serogroups ACWY hSBA titers ≥1:8 after 1 dose of MenABCWY vaccineA single dose of MenABCWY vaccine can be used as an alternative to
ACWY vaccines in ACWY-primed adolescentsStudy C3511001 | Evaluable Immunogenicity Population
Abbreviations: hSBA=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, seroresponse is a titer ≥4 times the 1:8. For those with a baseline
hSBA titer ≥1:8, seroresponse is a titer ≥4 times the baseline titer.
N=428- 442 for MenABCWY group; N=222- 227 for MenB -fHbp + MenACWY -CRM group.
Data on File, Study C3511001 (NCT04440163) Aug 2022, Pfizer Inc. Comparisons (ACWY -primed participants):
•MenABCWY vaccine 1 month after first dose
•MenACWY -CRM 1 month after single dose

18 Pfizer Confidential0102030405060708090100
A C W Y A22 A56 B24 B44 Composite%Percentage of participants achieving hSBA seroresponse*1 month after
vaccination
MenB -fHbp +       MenACWY -CRM MenABCWYSerogroups ACWY Serogroup B
•2 doses of MenABCWY vaccine were noninferior to 1 dose of MenACWY-CRM in ACWY- primed participants
•99-100% had serogroups ACWY hSBA titers ≥1:8 after 2 doses of MenABCWY vaccine
•100% of ACWY -primed participants have protective titers four years after 2 doses of MenABCWY vaccine (Study B1971057)2 doses of MenABCWY vaccine can be used as an alternative to 1 dose
MenACWY -CRM and 2 doses MenB -fHbp in ACWY -primed adolescentsStudy C3511001 | Evaluable Immunogenicity Population
Abbreviations: hSBA=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 t iter ≥1:4 and <1:8, seroresponse is a titer ≥4 times the 1:8. For those with a baseline
hSBA titer ≥1:8, seroresponse is a titer ≥4 times the baseline titer.N=376- 387 for MenABCWY group; N=22- 227 for MenB -fHbp + MenACWY -CRM group.
Data on File, Study C3511001 (NCT04440163) and Study B1971057 (NCT03135834) Aug 2022, Pfizer Inc
Comparisons (ACWY -primed participants):
•MenABCWY vaccine 1 month after second dose
•MenACWY -CRM 1 month after single dose
Comparisons (All participants group B vaccine naive):
•MenABCWY vaccine 1 month after second dose
•MenB -fHbp 1 month after second dose
19 Pfizer Confidential020406080100
Baseline 1m PD2 12m PD2 24m PD2 36m PD2 48m PD2Percentage (%)
020406080100
Baseline 1m PD2 12m PD2 24m PD2 36m PD2 48m PD2A
WC
Y020406080100
Baseline 1m PD2 12m PD2 24m PD2 36m PD2 48m PD2Percentage (%)
020406080100
Baseline 1m PD2 12m PD2 24m PD2 36m PD2 48m PD2
Baseline          7m PD1         18m PD1       30m PD1        42m PD1        54m PD1
Baseline          7m PD1        18m PD1       30m PD1        42m PD1        54m PD1Baseline         7m PD1         18m PD1       30m PD1        42m PD1       54m PD1
Baseline          7m PD1        18m PD1       30m PD1         42m PD1       54m PD1
MenABCWY MenB -fHbp + MenACWY -CRMMenACWY seroprotection persists up to 4 years in ACWY -primed populationStudy B1971057 | mITT and Booster Evaluable Immunogenicity Populations
Percentage of participants* (95% CI) with hSBA titers ≥ 1:8
Abbreviations: hSBA=serum bactericidal assay using human complement; PB=post booster; PD1=post dose 1; PD2=post dose 2.
*Number of subjects with valid and determinate hSBA titer for the given strain. Lower N for groups A, W, Y compared to C due to receipt of monovalent C vaccine prior to study entr y.
For groups A, W, and Y, N=48- 61 for MenABCWY and 22- 38 for MenB -fHbp + MenACWY -CRM (Stage 2 mITT population [baseline through 36m PD2/42m PD1]), and 32- 33 for MenABCWY and 16- 17 for MenB -
fHbp + MenACWY -CRM (Booster evaluable immunogenicity population [48m PD2 /54m PD1 Post Primary and Post Booster]). For group C, N=54- 100 for MenABCWY and 23- 72 for MenB -fHbp + MenACWY -
CRM (Stage 2 mITT population), and 68- 70 for MenABCWY and 51 for MenB -fHbp + MenACWY -CRM (Booster evaluable immunogenicity population).
Data on File, Study B1971057 (NCT03135834) Aug 2022, Pfizer Inc.
20 Pfizer ConfidentialSafety
21 Pfizer ConfidentialLocal reactions*within 7 days after vaccinationLocal reactogenicity by doseStudy C3511001 | Safety Population
0255075100 Percentage of participants (%)
0255075100Dose  1
Pain† Redness‡Swelling‡MenABCWY MenB -fHbp MenABCWY MenB -fHbp MenABCWY MenB -fHbpMenABCWY MenB -fHbp MenABCWY MenB -fHbp MenABCWY MenB -fHbp89.3% 85.1%
25.8%
19.5%24.9%21.4%
84.4%78.6%
23.2%
14.7%24.2%
14.7%Dose  2
Percentage of participants (%)
*Local reactions are summarized only for the left arm, which is the MenABCWYvaccine or MenB+fHbp injection site; †Mild=does not interfere with activity, moderate=interferes with activity, severe=prevents daily activity.
‡Mild=>2.0 to 5.0 cm, moderate=>5.0 to 10.0 cm, and severe is >10.0 cm.
Data on File, Study C3511001 (NCT04440163) Aug 2022, Pfizer Inc.Mild Moderate SevereSeverity10-25 years
No differences observed between: ACWY -Naïve and Primed participants or Primary and Booster vaccination
22 Pfizer ConfidentialSystemic events within 7 days after vaccinationSystemic reactogenicity by doseStudy C3511001 | Safety Population
1   e Dos 2   e Dos0255075100
MenABCWY MenB -fHbp +
MenACWY -CRM*46.8%52.1%54.7%
25.7%27.4%
20.2%22.6%46.9%
Fatigue† Headache† Muscle Pain† Joint Pain†Percentage of participants (%)
MenABCWY MenB -fHbp +
MenACWY -CRM*MenABCWYMenB -fHbp +
MenACWY -CRM*MenABCWY MenB -fHbp +
MenACWY -CRM*
0255075100
39.8%47.6%43.6%
22.8% 22.2% 18.3%15.6%37.8%
MenABCWY MenB -fHbp * MenABCWYMenB -fHbp * MenABCWY MenB -fHbp * MenABCWY MenB -fHbp *Percentage of participants (%)Mild Moderate SevereSeverity
*MenB -fHbp + MenACWY -CRM group: MenB -fHbp and MenACWY -CRM given at dose 1 and 3, MenB -fHbp given at dose 2.
†Mild: does not interfere with activity; Moderate: some interference with activity; Severe: prevents daily routine activity.
Data on File, Study C3511001 (NCT04440163) Aug 2022, Pfizer Inc.10-25 years
No differences observed between: ACWY -Naïve and Primed participants or Primary and Booster vaccination
23 Pfizer Confidential0255075100Dose  1 Dose  2MenABCWY MenB -fHbp +
MenACWY -CRM*11.0%20.1% 19.6%
3.2% 3.0%5.9% 5.8%13.5%
Chills† Diarrhea‡ Vomiting§ FeverǁMenABCWY MenB -fHbp +
MenACWY -CRM*MenABCWYMenB -fHbp +
MenACWY -CRM*MenABCWY MenB -fHbp +
MenACWY -CRM*
0255075100
8.2%16.4% 16.2%
1.5% 0.9% 2.3% 1.5%8.5%
MenABCWY MenB -fHbp * MenABCWYMenB -fHbp * MenABCWY MenB -fHbp * MenABCWY MenB -fHbp *Percentage of participants (%) Percentage of participants (%)38.0- 38.4 39.0- 40.0 38.5- 38.9Systemic events within 7 days after vaccinationSystemic reactogenicity by doseStudy C3511001 | Safety Population
*MenB -fHbp + MenACWY -CRM group: MenB -fHbp and MenACWY -CRM given at dose 1 and 3, MenB -fHbp given at dose 2. †Mild: does not interfere with activity; Moderate: some interference with activity;
Severe: prevents daily routine activity. ‡Mild: 2 –3 loose stools in 24 hours; Moderate: 4– 5 loose stools in 24 hours; Severe: 6 or more loose stools in 24 hours.
§Mild: 1 –2 times in 24 hours; Moderate: >2 times in 24 hours; Severe: requires intravenous hydration. ǁNofevers >40oCwere reported.
Data on File, Study C3511001 (NCT04440163) Aug 2022, Pfizer Inc.10-25 years
Moderate Mild SevereSeverity
Fever Severity (oC)
No differences observed between: ACWY -Naïve and Primed participants or Primary and Booster vaccination
24 Pfizer ConfidentialNumber (%) of participants reporting ≥ 1 adverse event during the vaccination phase*
MenABCWY + Saline
N=1763MenB-fHbp + MenACWY -CRM
N=649
Endpointn % (95% CI)Number of
Events n % (95% CI)Number of
Events
All AEs 368 20.9 (19.0, 22.8) 638 132 20.3 (17.3, 23.6) 202
Related 11 0.6 (0.3, 1.1) 19 4 0.6 (0.2, 1.6) 5
Severe 13 0.7 (0.4, 1.3) 17 4 0.6 (0.2, 1.6) 4
All SAEs 7 0.4 (0.2, 0.8) 9 0 0 (0.0, 0.6) 0
Related 0 0 (0.0, 0.2) 0 0 0 (0.0, 0.6) 0
All MAEs 263 14.9 (13.3, 16.7) 436 93 14.3 (11.7, 17.3) 141
Related 2 0.1 (0.0, 0.4) 2 1 0.2 (0.0, 0.9) 1
Severe 8 0.5 (0.2, 0.9) 9 3 0.5 (0.1, 1.3) 3
All NDCMCs 20 1.1 (0.7, 1.7) 23 2 0.3 (0.0, 1.1) 2
Related 0 0 (0.0, 0.2) 0 0 0 (0.0, 0.6) 0
Severe 1 <0.1 (0.0, 0.3) 2 0 0 (0.0, 0.6) 0Study C3511001 | Safety Population
Abbreviations: AE=adverse event; MAE=medically attended event (nonserious AE that results in an evaluation at a medical facil ity); NDCMC=newly diagnosed chronic medical condition (a disease
or medical condition, not previously identified, that is expected to be persistent or is otherwise long- lasting in its effects); SAE=serious adverse event.
*Vaccination phase refers to the time from the first study vaccination (Visit 1) through 1 month after the second study vacci nation (Visit 4).
Data on File, Study C3511001 (NCT04440163) Aug 2022, Pfizer Inc.
Higher number of NDCMCs of ADHD in the MenABCWY group – most of them with ADHD- related symptoms before
entering the study10-25 years
25 Pfizer ConfidentialOverall conclusion: Data support the use of MenABCWY vaccine in the
US adolescent meningococcal vaccination platform
•MenABCWY vaccine was safe and well tolerated in adolescents and young adults
Safety
•A single dose of MenABCWY vaccine can be used as an alternative to ACWY vaccines in
ACWY -naïve or primed adolescents and young adults
ACWY protection
•MenABCWY vaccine protects against all 5 serogroups with 2 doses given 6 to 12 months
apart
•Booster response was observed following a dose of MenABCWY vaccine 4 years after a 2 dose primary series (0,6m) for all 5 serogroups
•If 2 doses of MenABCWY vaccine are administered at 11-12 yrsof age, data support that a
single (booster) dose from 16 years of age can provide protection against all 5 serogroups
ABCWY protection
26 Pfizer ConfidentialPfizer wishes to thank:
•The clinical trial participants
•Sites, investigators, CRO, our partners, and their staffA
cknowledgements

Summary: 1 Pfizer ConfidentialMenABCWY  Meningococcal  Vaccine Jason D. Maguire, MD, MPH Clinical Lead, Phase 3 Program  Pfizer Vaccines Clinical R&D 2 Pfizer Confidential For Internal and Restricted Pfizer Use Only –Not for Distribution. Privileged and Confidential.MenABCWY vaccine composition Confidential•MenABCWY vaccine is composed of drug substance from: –Trumenba®(MenB-fHbp): licensed in the US for the prevention of invasive disease caused by Neisseria meningitidis group  B in individuals 10…