06 COVID Miller 508

1
Booster Doses of Moderna COVID -19 Vaccines in Adults,
Adolescents & Children
ACIP
September 1, 2022
Jacqueline Miller, MD
2Indication for Use of Moderna COVID -19 Vaccine, Bivalent
(Original And Omicron BA.4/BA.5)
EUA of Aug 31, 2022
Moderna COVID -19 Vaccine, Bivalent (Original And
Omicron BA.4/BA.5) is authorized for use in individuals 18
years of age and older as a single booster dose
administered at least 2 months after either:
▪Completion of primary vaccination with any authorized
or approved monovalent1COVID -19 vaccine, or
▪Receipt of the most recent booster dose with any
authorized or approved monovalent COVID -19
vaccine.
1Monovalent refers to any authorized or approved COVID -19 vaccine that contains or encodes the spike protein of only the Original SARS -CoV-2.

3
Rationale for Variant -Containing Booster Vaccines
▪Goals of variant -containing booster vaccines1,2
▪Retain neutralization for Original SARS -CoV-2
▪Stronger immune response against current variants
▪Broader cross -neutralization against future variants
▪Extend durability of protection
1. FDA Briefing Document for June 26, 2022 VRBPAC Meeting.
2. WHO Interim Statement on the Composition of Current COVID -19 Vaccines (June 17, 2022).
4Moderna COVID -19 Investigational Variant -containing
Vaccine Candidates Evaluated In Clinical Trials
▪Extensive evaluation of 3 monovalent and 4 bivalent investigational variant vaccines in
past year
▪>7,000 individuals boosted across all variant vaccine candidates
▪Bivalent vaccine candidates include :
25 µg
Original SARS -CoV-2
Beta -
containing vaccine
(mRNA -1273.211)
25 µg
Beta Variant
(B.1.351)
BA.1 Omicron -
containing vaccine
(mRNA -1273.214)
25 µg
Original SARS -CoV-2
25 µg
Omicron Variant
(BA.1)
BA.4/BA.5 Omicron -
containing vaccine
(mRNA -1273.222)
25 µg
Original SARS -CoV-2
25 µg
Omicron Variant
(BA.4/BA.5)
5
Clinical Studies of Booster Doses of Bivalent
Vaccines in Adults
6
Clinical Studies with Moderna COVID -19 Investigational
Bivalent Vaccine Candidates in Adults (≥ 18 Years of Age)
▪All participants previous received a primary series of mRNA -1273 (100 g); participants in Parts G & H
also previously received a 3rddose (50 µg) of mRNA -1273
▪Part G enrolled Mar 8 -23, 2022; Part H enrolled Aug 10 -23, 2022Bivalent Vaccine Study (Part) Dose NMedian
Follow -up
Beta
(mRNA -1273.211)205 (A)3rd (1st
booster)300 245 days
BA.1 Omicron
(mRNA -1273.214)205 (G)4th (2nd
booster)437 43 days
BA.4/BA.5 Omicron
(mRNA -1273.222)205 (H)4th (2nd
booster) 512 Ongoing
Total 1249
Chalkias et al. Research Squa re 2022, doi: 10.21203/rs.3.rs -1555201/v1; in press Nat Med
Chalkias et al. medRxiv 2022, doi: 10.1101/2022.06.24.22276703; in press New Engl J Med
7Study of 4thDose (2ndBooster) in Adults Using BA.1 Omicron
Bivalent Vaccine (mRNA -1273.214) -
Demographics and Baseline Characteristics
Study 205, Safety Set
Characteristic4thDose (2ndBooster)
Original
(mRNA -1273)
N = 377BA.1 Omicron
Bivalent
(mRNA -1273.214)
N = 437
Mean Age -Years (range) 57.5 (20, 96) 57.3 (20, 88)
≥ 65 years 39.8% 39.8%
Female 50.7% 59.0%
Non-White Race 14.6% 12.8%
Hispanic / Latino Ethnicity 9.8% 10.5%
Interval between 2ndand 3rdDose
(months) –median (range)8.0 (5.6, 14.4) 8.0 (4.7, 15.0)
Interval between 3rdand 4thDose
(months) –median (range)4.4 (3.0, 10.2) 4.5 (2.9, 13.4)
Prior SARS -CoV-2 Infection 26.8% 22.0%
Chalkias et al. medRxiv 2022, doi: 10.1101/2022.06.24.22276703; in press New Engl J Med
8
Solicited local adverse reactions within 7 days after injection. No Grade 4 events reported.
2nddose mRNA -1273 (Baden et al, NEJM 2021); 3rddose mRNA -1273 (Choi et al, Nat Med 2022); 4thdose mRNA -1273.214 ( Chalkias et al. medRxiv 2022; in press New Engl J Med ).Local Reactogenicity of BA.1 Omicron Bivalent (mRNA -1273.214) as 4thDose
Similar to 2ndDose of Primary Series and 3rdDose of Original (mRNA -1273) in
Adults
Study 205, Safety Set
88%84%
77%
9%5% 7%12%
5% 7%14%20%17%
0%20%40%60%80%100%Pain Erythema
Grade 1 -2Grade 3Axillary Swelling
or Tenderness
4thDose (2ndbooster) using BA.1 Omicron
(mRNA -1273.214)
N = 437Swelling
3rdDose (1stbooster) Original
(mRNA -1273)
N = 1672ndDose Original
(mRNA -1273)
N = 14,677
9Systemic Reactogenicity of BA.1 Omicron Bivalent (mRNA -1273.214) as 4th
Dose Generally Lower than 2ndDose of Primary Series and 3rdDose of
mRNA -1273 in Adults
Study 205, Safety Set
16%
7%4%59%55%
44%65%
59%55%58%
49%
40%43% 41%
31%
19%
11% 10%44%
35%
24%
0%20%40%60%80%100%Fever Headache Fatigue Myalgia ArthralgiaNausea /
VomitingChills
Solicited systemic adverse reactions within 7 days after injection. a) Grade 4 systemic reactions only with 2nddose of mRNA -1273 (<0.1%).
2nddose mRNA -1273 (Baden et al, NEJM , 2021); 3rddose mRNA -1273 (Choi et al, Nat Med , 2022); 4thdose mRNA -1273.214 ( Chalkias et al. medRxiv, 2022; in press New Engl J Med ).Grade 1 -2Grade 3a
4thDose (2ndbooster) using BA.1
Omicron bivalent (mRNA -1273.214)
N = 4373rdDose (1stbooster) Original
(mRNA -1273)
N = 1672ndDose Original
(mRNA -1273)
N = 14,677
10
Similar Overall Safety Profile of BA.1 Omicron Bivalent
(mRNA -1273.214) and Original mRNA -1273 as 4thDose (2ndBooster)
Study 205, Safety Set
Unsolicited AEs within 28 Days After Any Injectionn (%)
Original
(mRNA -1273)
N = 377BA.1 Omicron
Bivalent
(mRNA -1273.214)
N = 437
Any AE 78 (20.7%) 81 (18.5%)
SAE 1 (0.3%) 2 (0.5%)
Fatal AE 0 0
Medically Attended AE 52 (13.8%) 43 (9.8%)
AE Leading to Discontinuation from Study 0 0
Severe AE 3 (0.8%) 4 (0.9%)
11 Omicron BA.1 Neutralizing Titers Were Significantly Higher Following 4thDose
(2ndBooster) Using Omicron BA.1 Bivalent (mRNA -1273.214) than with mRNA -1273
Study 205, Per -Protocol Immunogenicity Set with No Prior Infection
1Based on ANCOVA model adjusting for age group (<65, ≥65 years) and pre -booster titer
2Common risk difference and 97.5% CI were calculated by Miettinen -Nurminen method adjusted for age group (<65, ≥65 years)
Chalkias et al. medRxiv 2022, doi: 10.1101/2022.06.24.22276703 –in press New Engl J MedSuccess
Criteria MetParameter                                   4thDose (2ndBooster)
Original
(mRNA -1273)
N = 260Omicron BA.1 Bivalent
(mRNA -1273.214)
(N = 334)
GMT Pre -booster
95% CI332
(282, 391)298
(259, 343)
GMT at Day 291
95% CI1421
(1283, 1574)2480
(2264, 2716)
GMT Ratio1(Bivalent vs Original)
97.5% CI1.75
(1.49, 2.04)
Seroresponse rate at Day 29
95% CI99.2%
(97.2, 99.9)100%
(98.9, 100)
Difference in seroresponse rates2
97.5% CI1.5
(-1.1, 4.0)
Superiority ofGMTs: Lower 97.5% CI of GMT Ratio > 1.0
Non-inferiority ofSeroresponse Rates: Lower 97.5% CI of difference > -10%
12 Original Strain (D614G) Neutralizing Titers Were Higher Following 4thDose (2ndBooster)
Using Omicron BA.1 Bivalent (mRNA -1273.214) than with mRNA -1273
Study 205, Per -Protocol Immunogenicity Set with No Prior Infection
1 Based on ANCOVA model adjusting for age group (<65, ≥65 years) and pre -booster titer
2Common risk difference and 97.5% CI (Miettinen -Nurminen) cannot be calculated when SRR in both group is 100%, absolute differen ce is reported.
Chalkias et al. medRxiv 2022, doi: 10.1101/2022.06.24.22276703 –in press New Engl J MedSuccess
Criteria MetParameter4thDose (2ndBooster)
Original
(mRNA -1273)
N = 260Omicron BA.1 Bivalent
(mRNA -1273.214)
(N = 334)
GMT Pre -booster
95% CI1521
(1353, 1710)1267
(1120, 1432)
GMT at Day 291
95% CI5287
(4887, 5719)6422
(5990, 6886)
GMT Ratio1(Bivalent vs Original)
97.5% CI1.22
(1.08,1.37)
Seroresponse rate at Day 29
95% CI100%
(98.9, 100)100%
(98.6, 100)
Difference in seroresponse rates2
97.5% CI0
Non-inferiority ofGMTs: Lower 97.5% CI of GMT Ratio >0.67
Non-inferiority ofSeroresponse Rates: Lower 97.5% CI of difference > -10%
13
3.8-fold
rise
7.1-fold
rise
4.4-fold
rise
8.0-fold
rise
2.5-fold
rise
4.8-fold
rise
512
3321558 1933
14733886
432
29816153070
23727676
2002,00020,000
All Participants SARS-CoV-2 Negative Pre-Booster SARS-CoV-2 Positive Pre-BoosterOmicron BA.1 Neutralizing Titers After 4thDose (2ndBooster) Significantly
Higher with BA.1 Omicron Bivalent (mRNA -1273.214) than mRNA -1273 in Adults
Study 205, Per -Protocol Immunogenicity Set
Omicron
Neutralizing
Antibody
ID50 GMT
(95% CI)
All Participants
 No Prior Infection
 Prior Infection
Omicron BA.1 Bivalent
(mRNA -1273.214)Original
(mRNA -1273) (N = 367) (N = 428) (N = 260) (N = 334) (N = 98) (N = 94)Pre
BoostDay
29Pre
BoostDay
29Pre
BoostDay
29Pre
BoostDay
29Pre
BoostDay
29Pre
BoostDay
29
GMR: 1.78
95% CI: 1.56, 2.04
GMR: 1.75
95% CI: 1.49, 2.04
GMR: 1.90
95% CI: 1.50, 2.40
Chalkias et al. medRxiv 2022, doi: 10.1101/2022.06.24.22276703;
in press New Engl J Med
14
18 –< 65 years
 ≥ 65 years
 18 –< 65 years
 ≥ 65 yearsOmicron BA.1 and Original Strain (D614G) Neutralizing Titers After 4thDose (2nd
Booster) of BA.1 Omicron Bivalent Were Consistent in Persons ≥65 Years of Age
Study 205, Per -Protocol Immunogenicity Set with No Prior Infection
13041820
30037344947378
12351811
11111522
28431951987272
22292590
1001,00010,000
18-<65 - Ancestral 65+ - Ancestral 18-<65 - Omicron 65+ - OmicronNeutralizing
Antibody
ID50 GMT
(95% CI)
Original SARS -CoV-2
Pre
BoostDay
29Pre
BoostDay
29
BA.1 Omicron Bivalent
(mRNA -1273.214)Original
(mRNA -1273) (N = 120) (N = 139)Pre
BoostDay
29Pre
BoostDay
29Pre
BoostDay
29Pre
BoostDay
29Pre
BoostDay
29Pre
BoostDay
29
Omicron BA.1
(N = 120) (N = 139) (N = 140) (N = 195) (N = 140) (N = 195)
VRBPAC, June 28, 2022 https://www.fda.gov/media/159492/download
15
Omicron B.1 and Original Strain (D614G) Neutralizing Antibodies After 4th
Dose (2ndBooster) Comparable Across Racial Groups
Study 205, Per -Protocol Immunogenicity Set with No Prior Infection
(N=316) (N=376) (N=316) (N=376) (N=26) (N=30) (N=26) (N=30) (N=25) (N=22) (N=25) (N=22)
PBD29PBD29 PBD29PBD29PBD29PBD29PBD29PBD29PBD29PBD29PBD29PBD29101001,00010,000100,000
3092333
207699
3403352
3232114
2942308
3431520 12346086
14585639
12236988
10354685
12735894
15535700Neutralizing Antibody
(GM Titer, 95%CI)Black/African
AmericanOther White
N=234     N=291         N=11        N=24        N=15        N=19       N=234      N=291       N=11        N=24        N=15        N=19
Prototype (mRNA-1273) Vaccine 50 μg BA.1 Omicron Bivalent Vaccine (mRNA-1273.214) 50 μg Omicron Original SARS-CoV-2
Black/African
AmericanOther White
Pre-booster ( PB), Day 29 post -boost ( D29)
164thDose (2ndBooster) with BA.1 Omicron Bivalent Booster (mRNA -
1273.214) Resulted in Higher Neutralizing Antibody Titers against Omicron
BA.4 & BA.5 than mRNA -1273 in Adults
Pre-booster ( PB), Day 29 post -boost ( D29)
PBD29PBD29PBD29PBD29 PBD29PBD29101001,00010,000
7202337
6091271
116727
140492
173941
209645Neutralizing Antibody
(GM Titer, 95%CI)No Prior InfectionPrior Infection All Participants
N=367        N=428        N=260       N=334           N=98          N=94
Original (mRNA-1273) 50 μg BA.1 Omicron Bivalent Vaccine (mRNA-1273.214) 50 μg
174th Dose (2ndBooster) with BA.1 Omicron Bivalent Booster (mRNA -1273.214)
Resulted in Higher Neutralizing Antibody Titers against Omicron BA.4/BA.5
Across Age Groups, Including ≥65 Year Olds, than mRNA -1273
Pre-booster ( PB), Day 29 post -boost ( D29)
PBD29PBD29PBD29PBD29PBD29PBD29PBD29PBD29PBD29PBD29PBD29PBD29101001,00010,000
8442783
5321375
6582118
6311245
132817
161588
105670
123422
1901039
192679
162879
222624Neutralizing Antibody
(GM Titer, 95%CI)No Prior Infection Prior Infection All Participants
Original (mRNA-1273) 50 μg BA.1 Omicron Bivalent Vaccine (mRNA-1273.214) 50 μgN=221       N=255      N=146       N=173       N=140      N=195       N= 120     N= 139       N=78        N=60         N=20         N=3418-64 yrs ≥65 yrs 18-64 yrs ≥65 yrs 18-64 yrs ≥65 yrs
18
GMR –ratio of GMT of BA.1 Omicron bivalent/GMT of mRNA -1273 at day 29
VOC –Variant of Concern
Meso Scale Discovery (MSD) Assay. Nominal alpha = 0.05.
mRNA -1273 N = 350 -351; mRNA -1273.214 N = 398 -402Binding Antibody Titers Against VOCs Are Significantly Higher after 4thDose
(2ndBooster) with BA.1 Omicron Bivalent (mRNA -1273.214) than mRNA -1273 in
Adults
Study 205, Per -Protocol Immunogenicity Set
569
353502
384652
403546
442
1001,000
Alpha Beta Delta GammaBinding
Antibody
Titer GMT
(AU/mL) at
Day 29
(95% CI)
GMR: 1.17
95% CI: 1.09, 1.24
Alpha
GMR: 1.14
95% CI: 1.07, 1.22
Beta
GMR: 1.10
95% CI: 1.03, 1.16
Delta
GMR: 1.16
95% CI: 1.09, 1.24
Gamma
500
BA.1 Omicron Bivalent
(mRNA -1273.214)Original
(mRNA -1273) Thousands
19
19
Bivalent Beta Vaccine (mRNA -1273.211) as 3rd Dose Elicited Higher
Neutralizing Antibody Responses in Adults through 6 Months Compared to
mRNA -1273
Study 205 Part A & Study 201 Part B, Per -Protocol Immunogenicity Set, No Prior Infection
Geometric Mean Ratio –GMT of bivalent beta vaccine (mRNA.1273.211)/GMT of original mRNA -1273 vaccine ofvramRNA -
1273 N = 149; Bivalent Beta vaccine (mRNA -1273.211) N = 295
Chalkias et al. Research Square 2022, doi: 10.21203/rs.3.rs -1555201/v1 –in press Nature Medicine
20
Pre-Clinical Studies of Booster Doses of Bivalent
BA.4/5 -Containing Vaccine (mRNA -1273.222) in
Mice
21
Increased Immunogenicity after Booster Dose of the BA.1 & BA.4/BA.5
Omicron Bivalent Vaccines (mRNA -1273.214 & mRNA -1273.222) in Mice
BA.1, pre and post boost comparison•K18 hACE2 mice previously vaccinated with primary series of mRNA -1273 (n = 8 -10 per group)
•Boosted with Original (mRNA -1273),  BA.1 Omicron Bivalent (mRNA -1273.214), or BA.4/BA.5 Bivalent (mRNA -
1273.222
•~31 weeks between primary series & booster
•Low 0.25 µg dose used to allow for differences between dose regimens to be captured
Neutralization (before and 4 weeks after booster)
Scheaffer et al, manuscript under preparationBA.1 neuts:
•7-and 3 -fold increase from bivalent
vaccines
BA.5 neuts:
•4.2-and 4.5 -fold increase from
bivalent vaccines
Limited boost from mRNA -1273 ns –not significant
*   p <0.05
**  p <0.01
PBS = 1273 primary series + PBS boosterBA.5, pre and post boost comparison
22
Increased Protection from BA.5 Challenge after Booster Dose of BA.4/BA.5
& BA.1 Omicron Vaccines (mRNA -1273.214 & mRNA -1273.222) in Mice
Scheaffer et al, manuscript under preparationBivalent vaccines
better protect from
BA.5 infection in lungs
ns –not significant
*       p <0.05
**      p <0.01
***    p <0.001
****   p <0.0001
Control = PBS primary series & booster
PBS = 1273 primary series + PBS booster•Mice challenged with 104PFU of BA.5 virus 4 weeks after booster dose

23
Ongoing Studies of Booster Doses in Adolescents
and Children, 6 Months -17 Years of Age
24
24Studies of Booster Dose of Original (mRNA -1273) Vaccine
inAdolescents & Children, 6 -17 Years
Studies 203 & 204
•3rddose (1stbooster) administered after completion of primary series
Study AgeBooster
DoseMonths between
2ndDose &
Booster (range) N
203 12-17 years 50 g 10.4 (9.0, 13.9) 1346
204 6-11 years 25 g 7.4 (4.1, 12.4) 1294
•Submission of data to the FDA is ongoing
25
25Ongoing Study of BA.1 Omicron Bivalent Vaccine (mRNA -1273.214)
Primary Series & Booster Dose in Infants & Children, 6 Months -5 Years
Study 306
•Open -label, Phase 3 study to evaluate safety & immunogenicity
Part History Vaccine Series Vaccine
Dose N Status
1 Vaccine
naive2-dose
primary series25 g 480
(320 2 -5 years;
160 6 -23 months)Enrollment ongoing
2 Previously
received
primary
series1 booster dose 10 g 480
(320 2 -5 years;
160 6 -23 months) 2-5 year olds fully
enrolled
Enrollment ongoing
for 6-23 month olds
26
Summary of Moderna COVID -19 Vaccine Booster Program
Immunogenicity
Safety ▪Vaccine boosters generally well tolerated in adults ≥18 years
▪Local and systemic reactogenicity of BA.1 Omicron bivalent as 4th dose similar to or lower
than 2nd dose of primary series & 3rd dose of original vaccine (mRNA -1273) in adults
▪No new safety concerns identified
▪Pre-specified immunogenicity objectives met for booster doses in adults
▪BA.1 Omicron bivalent in adults demonstrated:
▪Superior responses against BA.1 Omicron compared to Original mRNA -1273 booster in subjects
who were antibody negative pre -booster
▪Significantly higher neutralizing GMT against both BA.4/BA.5 Omicron & Original (D614G) in
subjects who were anti -N negative pre -booster
▪Significantly higher binding titers against Alpha, Beta, Delta and Gamma, confirming a broad
immune response regardless of VOC
▪Consistent immunogenicity across all ages (including ≥65 year olds)
▪Beta-containing bivalent in adults demonstrated improved durability of neutralizing
antibodies against VOC through 6 months compared to the original vaccine
▪Studies of BA.4/BA.5 Omicron bivalent booster in adults & BA.1 Omicron bivalent booster
in children 6 months -5 years ongoing
27
THANK YOU to Our Study Collaborators,
Investigators, and Participants
•All investigators
•Study site personnel
•Most importantly, the individuals who participated in these trials and
their families

Summary: 1 Booster Doses of Moderna COVID -19 Vaccines in Adults,  Adolescents & Children ACIP September 1, 2022 Jacqueline Miller, MD 2Indication for Use of Moderna COVID -19 Vaccine, Bivalent  (Original And Omicron BA.4/BA.5) EUA of Aug 31, 2022 Moderna COVID -19 Vaccine, Bivalent (Original And  Omicron BA.4/BA.5) is authorized for use in individuals 18  years of age and older as a single booster dose  administered at least 2 months after either: ▪Completion of primary vaccination with any…


03 COVID Klein Shimabukuro 508

cdc.gov/coronavirusSafety update of 1stbooster mRNA
COVID -19 vaccination
Advisory Committee on Immunization Practices
(ACIP)
April 20, 2022
Nicola Klein, MD, PhD
Kaiser Permanente Vaccine Study Center
Kaiser Permanente Northern CaliforniaTom Shimabukuro, MD, MPH, MBA
Vaccine Safety TeamCDC COVID- 19 Vaccine Task Force
Safety Surveillance of 1stBooster Doses in the Vaccine
Safety Datalink
Nicola Klein, MD, PhD
Kaiser Permanente Vaccine Study Center
Kaiser Permanente Northern California

Vaccine Safety Datalink (VSD)
•Established in 1990
•Collaborative project between CDC and 9 integrated healthcare organizations
•Includes ~ 12 million individuals across all sites
3
VSD 1stBoosters by Primary Series Vaccination
Data Through April 9th, 2022
4

VSD 1stBooster Dose by Demographics
5

VSD Rapid Cycle Analysis (RCA) for Boosters
•Pre-specified surveillance outcomes were assessed during weekly
sequential monitoring after 1stCOVID- 19 booster vaccination*
‒Analyses assess the risk of pre- specified outcomes within 1– 21 days following a booster
vaccination compared with boosted individuals who are within 22– 42 days following the
booster dose, adjusting for age, sex, race/ethnicity, VSD site, time since primary series,
and calendar time.
‒Weekly sequential analyses will continue through 2022, with a one- sided p- value
threshold for signaling of 0.01.
‒Due to the association of myocarditis/pericarditis with primary mRNA vaccination, myocarditis/pericarditis cases after the 1
stbooster were also chart reviewed and
adjudicated using the CDC case definitions.
6*Rapid Cycle Analysis (RCA) to monitor the safety of COVID -19 vaccines in near real- time within the Vaccine Safety Datalink.
Available at https://www.cdc.gov/vaccinesafety/pdf/COVID19 -RCA-Protocol -1342- 508.pdf
Vaccinee with Outcome in the Risk Interval and a Concurrent Comparator
“Boosted Individuals Only”
On each calendar day that an outcome occurred
in a vaccinee (e.g., June 3), w e compared
vaccinees in their risk interval (day 1– 21) with
similar vaccinees in their comparison interval (day 22–42)
By similar, we mean they were in the same age group and of the same sex, race, and at the same VSD site
Comparison Interval 22–42 days post- vaccination 42 22 June 3
Vaccinated with Booster
May 31
Risk Interval 1–21 days post- vaccination21June 3
Vaccinated with
Booster May 30
7
Signals for Pre- specified Outcomes in 21- day Risk Interval Through 4/12/22
Primary series with Pfizer -Pfizer OR
Moderna -ModernaPfizer -
PfizerModerna -
ModernaJanssen
Signal after 1stBooster Pfizer OR Moderna Pfizer Moderna Pfizer Moderna Janssen
Outcome Event Signal?
Acute myocardial infarction No No No No No No
Appendicitis No No No No No No
Bell's palsy No No No No No No
Cerebral venous sinus thrombosis No No No - - No
Disseminated intravascular coagulation No No No No - No
Encephalitis / myelitis / encephalomyelitis No No No - - -
Guillain -Barre syndrome No No No No - No
Stroke, hemorrhagic No No No No No No
Stroke, ischemic No No No No No No
Immune thrombocytopenia No No No No No -
Myocarditis / pericarditis Yes No No No No No
Seizures No No No No No No
Transverse myelitis No No No - - -
Thrombotic thrombocytopenic purpura No No No - - No
Thrombosis with thrombocytopenia syndrome No No No - No -
Venous thromboembolism No No No No No No
Pulmonary embolism No No No No No No
8 “-” indicates that analyses are not yet possible.
VSD COVID- 19 RCA
1stBooster Dose
Myocarditis and Pericarditis –
Preliminary Chart Review Analysis
9
Myocarditis and Pericarditis: Electronic
Case Identification using ICD-10 Codes1
Code List (based on consultation with cardiologist)
•B33.22 Viral myocarditis
•B33.23 Viral pericarditis
•I30.* Acute pericarditis
•I40.* Acute myocarditis
•I51.4 Myocarditis, unspecified
•I31.9 Disease of the pericardium, unspecified
101Casedefinition excludes individuals with COVID -19 infection <30 days before
myocarditis/pericarditis diagnosis.
* Includes all subcodes.
Chart Review Summary: Myocarditis and Pericarditis
after a 1stmRNA COVID-19 Booster Vaccine
•All electronically- identified cases among all ages up to 98 days post
vaccination are being chart -reviewed.
•Chart review is completed for 271 cases through March (25 potential
cases pending).
•Adjudicators verified 139/271 (51%) myocarditis/pericarditis cases.
•12–39 years old: 53/68 (78%)
•40+ years old: 86/203 (42%)
11
Chart Review Summary: Verified Myocarditis and
Pericarditis cases after a 1stBooster Vaccine
1212–39 year olds 40+ year olds
Case verification (anytime after vaccination) 53/68 (78%) 86/203 (42%)
Male sex 38/53 (72%) 51/86 (59%)
History of COVID (>30 days prior to diagnosis) 10/53 (19%) 11/86 (13%)
History of myocarditis/pericarditis 2/53 (4%) 4/86 (5%)
Median age 25 years 68.5 years
Median time from vaccination to symptom onset 4 days 29.5 days
Adjudication diagnosis
Myocarditis 12/53 (23%) 12/86 (14%)
Pericarditis 12/53 (23%) 57/86 (66%)
Myopericarditis 29/53 (55%) 17/86 (20%)
Timing of Symptom Onset after 1stBooster: 53 Verified
Myocarditis and Pericarditis Cases in 12– 39-Year -Olds
13

Timing of Symptom Onset after 1stBooster: 86 Verified
Myocarditis and Pericarditis Cases in 40+ year -olds
14

1Comparison interval is 22– 42 days after booster dose.
2Adjusted for VSD site, 5- year age group, sex, race/ethnicity, calendar date, and time since primary series.
3“Either” includes heterologous and homologous primary -> booster doses. Product specific analyses include only homologous primar y->booster doses.
4Two additional cases were in the risk interval but were not included because there were no appropriate comparators. These cas es are included in the events/million dose calculation.Analysis
Ages VaccineEvents
inRisk
IntervalEvents in
Comparison
Interval1Adjusted
Rate Ratio295%
Confidence
Interval2-Sided
P-valueEvents/Million
Doses
1st
Booster312–39 Either 28 10 4.89 2.24 –11.31 <0.001 20.3 (13.5 –29.3)
12–39 Pfizer 18 6 5.14 1.86 –15.90 0.001 21.4 (12.7 –33.8)
12–39 Moderna45 3 3.64 0.79 –19.45 0.097 17.0 (6.8 –35.0)Verified Myocarditis and Pericarditis in the 0–7 Day Risk Interval
Compared with Events on the Same Calendar Days Among Primary Series and Boosted Comparators
15
1Comparison interval is 22– 42 days after booster dose.
2Adjusted for VSD site, 5- year age group, sex, race/ethnicity, calendar date, and time since primary series.
3“Either” includes heterologous and homologous primary -> booster doses. Product specific analyses include only homologous primar y-> booster doses.
4Two additional cases were in the risk interval but were not included because there were no appropriate comparators. These cas es are included in the events/million dose calculation.
5One additional case was in the risk interval but not included because there were no appropriate comparators. This case is inc luded in the events/million dose calculation.Analysis
Ages VaccineEvents in Risk
IntervalEvents in
Comparison
Interval1Adjusted
Rate Ratio295%
Confidence
Interval2-Sided
P-valueEvents/Million
Doses
Primary,
Dose 212–39 Either 112 14 24.38 14.00 –44.96 <0.001 38.2 (31.5 –45.9)
12–39 Pfizer 83 10 28.07 14.63 –58.50 <0.001 41.4 (33.1 –51.1)
12–39 Moderna 28 3 24.49 7.82 –105.14 <0.001 30.8 (20.5 –44.5)
1st
Booster312–39 Either 28 10 4.89 2.24 –11.31 <0.001 20.3 (13.5 –29.3)
12–39 Pfizer 18 6 5.14 1.86 –15.90 0.001 21.4 (12.7 –33.8)
12–39 Moderna45 3 3.64 0.79 –19.45 0.097 17.0 (6.8 –35.0)Verified Myocarditis and Pericarditis in the 0–7 Day Risk Interval
Compared with Events on the Same Calendar Days Among Primary Series and Boosted Comparators
16
1Comparison interval is 22– 42 days after booster dose.
2Adjusted for VSD site, 5- year age group, sex, race/ethnicity, calendar date, and time since primary series.
3“Either” includes heterologous and homologous primary -> booster doses. Product specific analyses include only homologous primar y->booster doses.
4Two additional cases were in the risk interval but were not included because there were no appropriate comparators. These cas es are included in the events/million dose calculation.
5One additional case was in the risk interval but not included because there were no appropriate comparators. This case is inc luded in the events/million dose calculation.Analysis
Ages VaccineEvents
inRisk
IntervalEvents in
Comparison
Interval1Adjusted
Rate Ratio295%
Confidence
Interval2-Sided
P-valueEvents/Million
Doses
1st
Booster312–39 Either 28 10 4.89 2.24 –11.31 <0.001 20.3 (13.5 –29.3)
12–39 Pfizer 18 6 5.14 1.86 –15.90 0.001 21.4 (12.7 –33.8)
12–39 Moderna45 3 3.64 0.79 –19.45 0.097 17.0 (6.8 –35.0)
40+ Either511 15 2.30 0.95 –5.43 0.063 4.0 (2.1 –7.0)
40+ Pfizer54 5 1.65 0.34 –7.31 0.509 3.3 (1.1 –7.6)
40+ Moderna44 8 1.85 0.43 –6.85 0.373 4.6 (1.7 –10.1)
17Verified Myocarditis and Pericarditis in the 0–7 Day Risk Interval
Compared with Events on the Same Calendar Days Among Primary Series and Boosted Comparators
1Comparison interval is 22– 42 days after booster dose.
2Adjusted for VSD site, 5- year age group, sex, race/ethnicity, calendar date, and time since primary series.
3“Either” includes heterologous and homologous primary -> booster doses. Product specific analyses include only homologous primar y-> booster doses.
4Two additional cases were in the risk interval but were not included because there were no appropriate comparators. These cas es are included in the events/million dose calculation.Analysis
Ages VaccineEvents
inRisk
IntervalEvents in
Comparison
Interval1Adjusted
Rate Ratio295%
Confidence
Interval2-Sided
P-valueEvents/Million
Doses
1st
Booster312–39 Either 30 10 1.90 0.91 –4.25 0.092 21.9 (14.8 –31.2)
12–39 Pfizer 19 6 2.07 0.79 –6.05 0.146 22.8 (13.7 –35.6)
12–39 Moderna46 3 1.36 0.33 –6.87 0.697 19.5 (8.4 –38.5)Verified Myocarditis and Pericarditis in the 0–21 Day Risk Interval
Compared with Events on the Same Calendar Days Among Primary Series and Boosted Comparators
18
1Comparison interval is 22– 42 days after booster dose.
2Adjusted for VSD site, 5- year age group, sex, race/ethnicity, calendar date, and time since primary series.
3“Either” includes heterologous and homologous primary -> booster doses. Product specific analyses include only homologous primar y-> booster doses.
4Two additional cases were in the risk interval but were not included because there were no appropriate comparators. These cas es are included in the events/million dose calculation.
5Four additional cases were in the risk interval but not included because there were no appropriate comparators. These cases are included in the events/million dose calculation.
6Three additional cases were in the risk interval but not included because there were no appropriate comparators. These cases areincluded in the events/million dose calculation.Analysis
Ages VaccineEvents
inRisk
IntervalEvents in
Comparison
Interval1Adjusted
Rate Ratio295%
Confidence
Interval2-Sided
P-valueEvents/Million
Doses
1st
Booster312–39 Either 30 10 1.90 0.91 –4.25 0.092 21.9 (14.8 –31.2)
12–39 Pfizer 19 6 2.07 0.79 –6.05 0.146 22.8 (13.7 –35.6)
12–39 Moderna46 3 1.36 0.33 –6.87 0.697 19.5 (8.4 –38.5)
40+ Either529 15 1.96 1.02 –3.88 0.044 11.0 (7.5 –15.4)
40+ Pfizer515 5 3.01 1.06 –9.68 0.038 12.5 (7.5 –19.5)
40+ Moderna69 8 1.28 0.42 –3.80 0.650 9.3 (4.8 –16.3)Verified Myocarditis and Pericarditis in the 0–21 Day Risk Interval
Compared with Events on the Same Calendar Days Among Primary Series and Boosted Comparators
19
Summary: Preliminary Findings of RCA Monitoring for 1st
Boosters
•In weekly surveillance, the only safety signal has been for myocarditis/pericarditis
in the 21 days after a 1stbooster dose.
•No other safety signals in weekly monitoring of pre- specified outcomes.
•Myocarditis/pericarditis differed between persons ages 12– 39 and 40+ years.
•12–39 years: mostly myocarditis and myopericarditis with onset <7 days after 1stbooster.
•40+ years: mostly pericarditis; cases more spread out in the 3 weeks after 1stbooster.
•For persons ages 12– 39 years, rate ratios for myocarditis/pericarditis 0– 7 days
after 1stbooster dose were elevated.
•Rate per million 1stbooster doses administered was not higher than after primary series dose
2 mRNA COVID -19 vaccination.
•For persons ages 40 years and older, rate ratios for myocarditis/pericarditis were elevated, but less so, in the 0– 7 and 0– 21 days after the 1
stbooster dose
compared with persons ages 12– 39 years.
•Surveillance is ongoing.
20
cdc.gov/coronavirusSafety update of 1stbooster mRNA
COVID -19 vaccination
Vaccine Adverse Event Reporting System (VAERS)
&
V-safe
Tom Shimabukuro, MD, MPH, MBA
Vaccine Safety Team
CDC COVID- 19 Vaccine Task Force
+co-managed by
CDC and FDA
Vaccine Adverse Event
Reporting System
http://vaers.hhs.govVAERS is the nation’s early warning system for vaccine safety
22
VAERS accepts reports from everyone
Key strengths
Rapidly detects potential
safety problems
Can detect rare adverse
eventsKey limitations
Passive surveillance system
Inconsistent quality and completeness of information
Reporting biases
Generally, cannot determine cause and effectRegardless of the plausibility of the vaccine causing the event or the
clinical seriousness of the event
23
U.S. reports to VAERS following 1stbooster mRNA COVID- 19
vaccination* (as of April 11, 2022)
24* Among persons receiving Pfizer -BioNTech dose 3: children and adolescents ages 12– 15 years vaccinated during Jan 3 – April 11, 2022, and ages 16– 17 years vaccinated during Dec 9, 2021 –
April 11, 2022; adults ages ≥18 years vaccinated during September 22, 2021 –April 11, 2022. Among persons receiving Moderna boo ster doses, adults ages ≥18 years vaccinated during October
20, 2021 –April 11, 2022. All reports received and processed as of April 11, 2022.
†Doses of Pfizer -BioNTech dose 3 administered among children and adolescents ages 12 –15 years during January 6 –Apr 14, 2022; a dolescents ages 16– 17 years during Dec 9, 2021 –April 14,
2022; adults ages ≥18 years during September 22, 2021 –April 14, 2022. Doses of Moderna dose 3 administered among adults ages ≥ 18 years during October 28, 2021 –April 14, 2022
‡ Sex was not reported in approximately 2% of reports.Proportions by seriousness and sex were comparable to primary series
•Most reports (90%) were non- serious
•Most reports (65%) were among femalesDoses
admin†Total
reportsMedian
ageMale‡
n (%)Female‡
n (%)Non -serious
n (%)Serious
n (%)
93,118,318 52,063 53 years 17,281 (33) 33,692 (65) 47,014 (90) 5,049 (10)
U.S. reports to VAERS following 1st
booster mRNA COVID -19 vaccination,
by race and ethnicity * (as of April 11, 2021) Race and ethnicity n (%)
Non -Hispanic White 25,508 (49)
Unknown or not reported 14,787 (28)
Hispanic† 3,616 (7)
Non -Hispanic Other 2,987 (6)
Non -Hispanic Black 2,264 (4)
Non -Hispanic Asian 1,764 (3)
Non -Hispanic multiracial 561 (1)
Non -Hispanic American
Indian/Alaskan Native520 (<1)
Non -Hispanic Native Hawaiian
or Other Pacific Islander56 (<1)
Total 52,063* Among persons receiving Pfizer -BioNTech dose 3: children and adolescents ages 12 –15 years
vaccinated during Jan 3 –April 11, 2022, and ages 16 –17 years vaccinated during Dec 9, 2021 –
April 11, 2022; adults ages ≥18 years vaccinated during September 22, 2021 –April 11, 2022.
Among persons receiving Moderna booster doses, adults ages ≥18 years vaccinated during October
20, 2021 – April 11, 2022. All reports received and processed as of April 11, 2022.
†Includes persons reported as of Hispanic ethnicity, but of unreported or unknown race.
25
Most frequently reported non- serious adverse events to VAERS following 1stbooster
mRNA COVID -19 vaccination (47,014 total non- serious reports) * (as of April 11, 2022)
26Rank Adverse event (not mutually exclusive) n (%)
1 Headache 6,119 (13)
2 Pyrexia 5,840 (12)
3 Pain 5,783 (12)
4 Fatigue 5,420 (12)
5 Expired Product Administered 5,082 (11)
6 Chills 4,836 (10)
7 Product Storage Error 4,030 (9)
8 Pain In Extremity 3,813 (8)
9 Nausea 3,209 (7)
10 Dizziness 2,982 (6)Non-serious reports (all reports) Non-serious reports (clinical outcomes)†
Rank Adverse event (not mutually exclusive) n (%)
1 Headache 6,119 (13)
2 Pyrexia 5,840 (12)
3 Pain 5,783 (12)
4 Fatigue 5,420 (12)
5 Chills 4,836 (10)
6 Pain In Extremity 3,813 (8)
7 Nausea 3,209 (7)
8 Dizziness 2,982 (6)
9 Urticaria 2,966 (6)
10 Lymphadenopathy 2,896 (6)
* Among persons receiving Pfizer -BioNTech dose 3: children and adolescents ages 12 –15 years vaccinated during Jan 3 – April 11, 2022, and ages 16 –17 years vaccinated during Dec 9,
2021 –April 11, 2022; adults ages ≥18 years vaccinated during September 22, 2021 –April 11, 2022. Among persons receiving Mode rna booster doses, adults ages ≥18 years vaccinated
during October 20, 2021 – April 11, 2022. All reports received and processed as of April 11, 2022.
† Determined by subject matter expert consensus
Most frequently reported serious adverse events to VAERS following 1stbooster
mRNA COVID -19 vaccination (5,049 total serious reports) (as of April 11, 2022)
27Rank Adverse event (not mutually exclusive) n (%)
1 Covid -19 1,196 (24)
2 Sars-Cov-2 Test Positive 997 (20)
3 Dyspnoea 817 (16)
4 Death 549 (11)
5 Chest Pain 440 (9)
6 Pyrexia 436 (9)
7 Asthenia 435 (9)
8 Condition Aggravated 396 (8)
9 Fatigue 386 (8)
10 Pain 369 (7)Serious reports (all reports) Serious reports (clinical outcomes)†
Rank Adverse event (not mutually exclusive) n (%)
1 Covid -19 1,196 (24)
2 Sars-Cov-2 Test Positive 997 (20)
3 Dyspnoea 817 (16)
4 Death 549 (11)
5 Chest Pain 440 (9)
6 Pyrexia 436 (9)
7 Asthenia 435 (9)
8 Fatigue 386 (8)
9 Pain 369 (7)
10 Cough 328 (7)
* Among persons receiving Pfizer -BioNTech dose 3: children and adolescents ages 12 –15 years vaccinated during Jan 3 – April 11, 2022, and ages 16 –17 years vaccinated during Dec 9,
2021 –April 11, 2022; adults ages ≥18 years vaccinated during September 22, 2021 –April 11, 2022. Among persons receiving Mode rna booster doses, adults ages ≥18 years vaccinated
during October 20, 2021 – April 11, 2022. All reports received and processed as of April 11, 2022.
† Determined by subject matter expert consensus
28Median age in myocarditis case reports is younger vs. pericarditis
Male predominance observed for myocarditis case reports but not for pericarditisMyocarditis (n=110) Pericarditis (n=38)
Median age (IQR†) 23 (16– 36) 46 (25– 62)
Median time to symptom onset (IQR†) 3 (2– 4) 3 (1– 7)
Male, n (%) / Female, n (%) 89 (81%) / 21 (19%) 18 (47%) / 20 (53%)U.S. reports to VAERS of myocarditis and pericarditis following 1stbooster
mRNA COVID -19 vaccination, by age, time to symptom onset, and sex*
(as of April 11, 2022)
* Among persons receiving Pfizer -BioNTech dose 3: children and adolescents ages 12 –15 years vaccinated during Jan 3 – April 11, 2022, and ages 16 –17 years vaccinated during Dec 9,
2021 –April 11, 2022; adults ages ≥18 years vaccinated during September 22, 2021 –April 11, 2022. Among persons receiving Mode rna booster doses, adults ages ≥18 years vaccinated
during October 20, 2021 – April 11, 2022. All reports received and processed as of April 11, 2022.
†Interquartile range.
29Most myocarditis
reports among ages 12–29 years
Pericarditis reports distributed fairly evenly among age groups*
024681012141618
12 to 15 16 to 17 18 to 24 25 to 29 30 to 39 40 to 49 50 to 64 65+Verified reports to VAERS
Age group, yearsMyocarditis or pericarditis following 1stmRNA COVID -19 booster
vaccination among males , days 0– 7, by age group, VAERS
Pfizer, myocarditis Moderna, myocarditis Pfizer, pericarditis Moderna, pericarditis
* Complicates estimation of reporting rates
024681012141618
12 to 15 16 to 17 18 to 24 25 to 29 30 to 39 40 to 49 50 to 64 65+Verified reports to VAERS
Age group, yearsMyocarditis or pericarditis following 1stmRNA COVID -19 booster
vaccination among males , days 0– 7, by age group, VAERS
Pfizer, myocarditis Moderna, myocarditis Pfizer, pericarditis Moderna, pericarditis
30Most myocarditis
reports among ages 12–29 years
Pericarditis reports distributed fairly evenly among age groups*
* Complicates estimation of reporting rates
31Most myocarditis
reports among ages 12–29 years
Pericarditis reports distributed fairly evenly among age groups*
* Complicates estimation of reporting rates024681012141618
12 to 15 16 to 17 18 to 24 25 to 29 30 to 39 40 to 49 50 to 64 65+Verified reports to VAERS
Age group, yearsMyocarditis or pericarditis following 1stmRNA COVID -19 booster
vaccination among males , days 0– 7, by age group, VAERS
Pfizer, myocarditis Moderna, myocarditis Pfizer, pericarditis Moderna, pericarditis
32Few reports among
females of either condition
Both myocarditis and pericarditis reports distributed fairly evenly among age groups
024681012141618
12 to 15 16 to 17 18 to 24 25 to 29 30 to 39 40 to 49 50 to 64 65+Verified reports to VAERS
Age group, yearsMyocarditis or pericarditis following 1stmRNA COVID -19 booster
vaccination among females , days 0– 7, by age group, VAERS
Pfizer, myocarditis Moderna, myocarditis Pfizer, pericarditis Moderna, pericarditis
Reporting rates of myocarditis (per 1 million doses administered) among
males following 1stmRNA COVID -19 booster vaccination, by risk interval*
41,670,922 1stmRNA COVID -
19 booster vaccinations
administered in males*
Reporting rates exceed background incidence in ages 12 –29 years
Reporting rates highest in males ages 16 –17 years,
followed by 12– 15 years
* Among persons receiving Pfizer -BioNTech dose 3: children and adolescents ages 12 –15 years vaccinated during Jan 3 – April 11, 2022, and ages 16 –17 years vaccinated during Dec 9,
2021 –April 11, 2022; adults ages ≥18 years vaccinated during September 22, 2021 –April 11, 2022. Among persons receiving Mode rna booster doses, adults ages ≥18 years
vaccinated during October 20, 2021 – April 11, 2022. All reports received and processed as of April 11, 2022. Doses administered as of April 14, 2022. An estimated 1 –10 cases of
myocarditis per 100,000 person years occurs among people in the United States, regardless of vaccination status; adjusted for day 0–7 and 0 –21 risk periods, this estimated
background is 0.2 to 2.2 per 1 million person risk period. 33Pfizer -BioNTech Moderna
age group Days 0 –7 Days 0 –7
12 to 15 17.2 N/A
16 to 17 23.2 N/A
18 to 24 5.4 12.1
25 to 29 4.8 4.0
30 to 39 1.5 1.5
40 to 49 0.0 <1.0
50 to 64 <1.0 0.0
65+ <1.0 <1.0
Clinical outcomes of myocarditis and pericarditis following 1stmRNA
COVID -19 booster vaccination*
93,118,318 total
booster doses
administered*
Patients not
hospitalized
received outpatient
care
Patients still recovering are
stable or improving
34* Doses of Pfizer -BioNTech dose 3 administered among children and adolescents ages 12 –15 years during January 6 –Apr 14, 2022; adolescents ages 16 –17 years during Dec 9,
2021 –April 14, 2022; adults ages ≥18 years during September 22, 2021 –April 14, 2022. Doses of Moderna dose 3 administered am ong adults ages ≥18 years during October 28,
2021 –April 14, 2022 Myocarditis
(N=110)Pericarditis
(N=38)
Hospitalized 90/110 (82%) 15/38 (39%)
Discharged 90/90 (100%) 15/15 (100%)
Known outcomes 86/90 (96%) 14/15 (93%)
Recovered from symptoms at
last follow up51/86 (59%) 10/14 (71%)
35Smartphone -based active safety monitoring
http:// cdc.gov/vsafe
Enroll yourself or
your dependent
after any dose!
Active safety monitoring for COVID -19 vaccines
v-safe is a CDC smart phone -based monitoring program for COVID- 19
vaccine safety in the U.S.
•Uses text messaging and web surveys to check in with vaccine recipients after
vaccination
•Can register at any time: after first, second, or third dose
•Solicits participants' reports on how they feel after COVID -19 vaccination
‒Local injection site reactions (i.e., pain, redness, swelling)
‒Systemic reactions (i.e., fatigue, headache, joint pain)
‒Health impacts (unable to perform normal daily activities, missed school or work, or received care)
36
Patterns of vaccination for 729,720 v -safe participants aged
≥18 years who reported a booster dose
Moderna (%) Pfizer -BioNTech (%) Janssen (%) Total
Moderna 311,374 (94) 17,034 23,211 351,619
Pfizer -BioNTech 19,538 336,618 (95) 13,685 369,841
Janssen 247 238 7,775 (17) 8,260
Total 331,159 353,890 44,671 729,720Primary series
Booster
dose
Data as of April 10, 2022. Includes participants who completed at least one survey in the first week after each dose (administered beginning
September 22, 2021 for Pfizer -BioNTech and October 20,2021 for Moderna and Janssen). 37
Demographic summary of 729,720 v -safe participants aged
≥18 years who reported a booster dose
Data as of April 10, 2022. Includes participants who completed at least one survey in the first week after each dose (administered beginning
September 22, 2021 for Pfizer -BioNTech and October 20,2021 for Moderna and Janssen).
Abbreviations: AI/AN = American Indian/Alaska Native; NHPI = Native Hawaiian or other Pacific Islander; AA=African American.Characteristic % of participants
Sex
Female 62.8
Male 36.4
Unknown 0.8
Age group (years)
18–49 268,632
50–64 189,735
65–74 210,566
75–84 56,051
≥85 4,736Characteristic % of participants
Ethnicity
Hispanic or Latino 6.7
Not Hispanic/ Latino 90.2
Unknown 3.1
Race
AI/AN 0.4
Asian 5.4
Black or AA 5.6
NHPI 0.2
White 82.9
Multiracial 1.8
Other 1.9
Unknown 1.8
38
Reactions and health impact events reported by v -safe participants aged ≥18 years at
least once in days 0– 7 after homologous Pfizer -BioNTech vaccination, by dose
Includes 336,618 participants who completed at least one survey in the first week after each dose, data collected during Sept emb er 22 –April 10, 2022
* Dose 2 compared to dose 3: statistically significant difference (p -value <0.05) using multivariable generalized estimating equ ations model that accounted for
the correlation between registrants and adjusted for demographic variables. 390102030405060708090100
Any injection site
reactionAny systemic reaction Any health impact Unable to perform
daily activitiesUnable to work Needed medical carePercentage
Dose 1 Dose 2 Booster* *
**
*
*
Reactions and health impact events reported by v -safe participants aged 12– 17 years
at least once in days 0– 7 after homologous Pfizer -BioNTech vaccination, by dose
Includes 3,694 participants who completed at least one survey in the first week after each dose, data collected during December 9, 2021– April 10, 2022
* Dose 2 compared to dose 3: statistically significant difference (p -value <0.05) using multivariable generalized estimating equ ations model that accounted for
the correlation between registrants and adjusted for demographic variables. 400102030405060708090100
Any injection site
reactionAny systemic reaction Any health impact Unable to perform
daily activitiesUnable to work or
attend schoolNeeded medical carePercentage
Dose 1 Dose 2 Booster*
*
*
*
*
Reactions and health impact events reported by v -safe participants aged ≥18 years at
least once in days 0– 7 after homologous Moderna vaccination, by dose
Includes 311,374 participants who completed at least one survey in the first week after each dose, data collected during Octo ber20–April 10, 2022
* Dose 2 compared to dose 3: statistically significant difference (p -value <0.05) using multivariable generalized estimating equ ations model that accounted for
the correlation between registrants and adjusted for demographic variables. 410102030405060708090100
Any injection site
reactionAny systemic reaction Any health impact Unable to perform
daily activitiesUnable to work Needed medical carePercentage
Dose 1 Dose 2 Booster**
*
**
Summary of the safety of 1stbooster
mRNA COVID -19 vaccination
42
Summary
VSD Rapid Cycle Analysis (RCA) monitoring
The only safety signal detected for any pre -specified outcome following 1stbooster dose has
been for myocarditis/pericarditis in the 21 days after mRNA COVID- 19 vaccination
Myocarditis/pericarditis differed between persons ages 12 –39 and 40+ years
•12–39 years: mostly myocarditis and myopericarditis with onset <7 days after vaccination
•40+ years: mostly pericarditis; cases more spread out in the 3 weeks after vaccination
For persons ages 12 –39 years, rate ratios for myocarditis/pericarditis 0 –7 days after 1st
booster dose were elevated
•Rate per million 1stbooster doses administered was not higher than after dose 2 mRNA
COVID -19 vaccination
For persons ages 40 years and older, rate ratios for myocarditis/pericarditis were elevated,
but less so in the 0 –7 and 0– 21 days after the 1stbooster dose compared to persons ages 12 –
39 years
43
Summary (cont.)
VAERS monitoring (after 93 million 1stmRNA COVID -19 booster vaccinations in the United Sates)
Local and systemic reactions are most commonly reported following 1stbooster dose
110 verified reports of myocarditis and 38 of pericarditis
•Myocarditis reporting rates were highest among young males (ages 12– 29 years)
‒Reporting rates for persons ages 12 –29 years following 1stbooster exceeded
background, but were lower compared to post -dose 2 rates with primary series
•Pericarditis reports were relatively rare, and distributed evenly among males and
females and among the varied age groups
•More myocarditis (82%) than pericarditis (39%) case patients were hospitalized
‒Most hospitalized patients recovered from symptoms at time of follow up*
V-safe monitoring
No unusual or unexpected findings or new safety concerns identified
44 *Follow up varies based on timing of the report and healthcare records availability
Summary (cont.)
45Active surveillance in VSD and passive surveillance in VAERS suggests an increased risk of
myocarditis/pericarditis following the 1stmRNA COVID- 19 booster vaccination
•For myocarditis, the findings are consistent with those observed with primary series vaccination, but the risk appears to be lower following the 1
stbooster dose compared
to dose 2 of primary series
‒Risk of myocarditis is highest in younger males with onset clustering within 0 –7
days of 1stbooster vaccination
‒Pericarditis is less common, more evenly distributed between males and females, and more evenly distributed across age groups
Local and systemic reactogenicity and health impacts appear similar or attenuated for 1st
mRNA COVID- 19 booster vaccination compared to dose 2 of primary series
Monitoring is ongoing
Acknowledgments
VAERS team
CISA team
VSD team
COVID -19 Vaccine Task Force Data Monitoring
and Reporting Group
CDC Immunization Safety Office
FDA/Center for Biologics Evaluation and Research
State and local health departments
Healthcare providers and other stakeholders
reporting to VAERS
V-safe team
V-safe participants
Anne Hause
James Baggs
Paige Marquez
Isaac McCullum
Bicheng Zhang
Tanya Myers
46Kaiser Permanente Northern California
•Nicky Klein, Laurie Aukes, Berwick Chan, Bruce Fireman, Kristin Goddard, Ned Lewis, Karen Nunley, Pat Ross, Arnold
Yee, Ousseny Zerbo, Nandini Bahkshi
Marshfield Clinic Research Institute
•Jim Donahue, Ed Belongia, Tom Boyce, Kayla Hanson, Burney Kieke, Dave McClure, Erica Scotty
CDC Immunization Safety Office
•Eric Weintraub, Tat’Yana Kenigsberg, Mike McNeil, Jonathan Duffy, Frank Destefano, Tanya Myers, Tom
Shimabukuro, Matt Oster
VSD Sites
•HealthPartners Institute, Minneapolis, Minnesota
•Kaiser Permanente Colorado, Denver, Colorado
•Kaiser Permanente Northwest, Portland, Oregon
•Kaiser Permanente Southern California, Los Angeles,
California
•Kaiser Permanente Washington, Seattle, Washington
•Denver Health, Denver, Colorado
For more information, contact CDC
1-800- CDC- INFO (232- 4636)
TTY:  1 -888- 232- 6348    www.cdc.gov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.
Thank you!

Summary: cdc.gov/coronavirusSafety update of 1stbooster mRNA       COVID -19 vaccination Advisory Committee on Immunization Practices  (ACIP) April 20, 2022 Nicola Klein, MD, PhD Kaiser Permanente Vaccine Study Center Kaiser Permanente Northern CaliforniaTom Shimabukuro, MD, MPH, MBA Vaccine Safety TeamCDC COVID- 19 Vaccine Task Force Safety Surveillance of 1stBooster Doses in the Vaccine  Safety Datalink Nicola Klein, MD, PhD Kaiser Permanente Vaccine Study Center Kaiser Permanente Northern…


03 Pneumococcal Self 508

Public
Interim Results from the PNEUMO Study
.
Pneumococcal pNeumonia Epidemiology, Urine serotyping, and
Mental Outcomes study
February 29, 2024
Study Leadership
Wesley H. Self, MD
Vanderbilt UniversityJ. Jackson Resser , MS
Vanderbilt UniversityKelly D. Johnson, PhDMerck & Co., Inc.
1 Funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USANadine Rouphael , MD
Emory University
Public
PNEUMO study overview
•Adults 18+ years hospitalized with
community acquired pneumonia (CAP)Target
Population
•Multi -country, prospective, population -
based active surveillance studyDesign
•Estimate pneumococcal pneumonia
incidence and serotype prevalence (using
Merck PCV15 and V116 SSUADs), with
longitudinal evaluation of functional status, quality of life and costObjectives►Incidence hospitalized pneumococcal CAP
►Incidence hospitalized PCV15-  and
V116 - type pneumococcal CAP
►Direct medical cost
►Work loss
►Functional status
►Cognitive status
►Quality of Life (EQ -5D)Up to 6
months
post -
discharge
2
Public
Pneumonia surveillance  with prospective, real -time enrollment of
adults hospitalized with CAP (including HCAP)
HCAP, healthcare associated pneumonia US PNEUMO sites: enrollment Sept 2018 - present
Nashville, Tennessee
(2 hospitals) Atlanta, Georgia
3
PublicEligibility criteria
Inclusion  Criteria
1.Age ≥ 18 years  old
2.Hospitalized
3.Clinical signs and/or  symptoms of an acute  respiratory  illness (e.g., new  shortness of breath,  cough)
4.Clinical signs and/or  symptoms of an acute  infection (e.g., fever,  leukocytosis)
5.Radiologic  evidence  of pneumonia  interpreted  by a radiologist  (x-ray or CT)
Exclusion  Criteria
1.Prior enrollment  in this study  within  the past  30 days  (to avoid  multiple  enrollments for same  episode  of
pneumonia).
2.Development  of pneumonia  >72 hours  after  hospital admission
3.Inability  to obtain  consent  within  72 hours  of hospital admission
4.Inability  or unwillingness of the patient  to provide  a urine  sample  within  72 hours  of hospital admission .
5.Non -pneumonia  illness completely  explains the patient’s  acute  symptoms.  4
Public
Tests for S. pneumoniae
•Urine collection from patients at enrollment
    (1) BinaxNow pneumococcal urinary antigen test (local testing by research team)

 (2) Serotype- specific urinary antigen detection (SSUAD) assays:
•Developed and performed by Merck laboratory
•30 serotypes:
•1, 3, 4, 5, 6A*, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15A, 15C#, 16F, 17F, 18C, 19A, 19F, 20A, 22F,
23A, 23B, 23F, 24F, 31, 33F, 35B
•All serotypes in PCV15, PCV20, and V116 included except 15B
•Results of clinically -obtained bacterial cultures:
•Sterile sites: blood, pleural fluid, BAL fluid, CSF, synovial fluid
•Non -sterile sites: high-quality respiratory samples (>25 WBC, <10 epi)
•sputum, endotracheal aspirate
5* assay for serotype 6A has cross- reactivity with serotype 6C
# assay for serotype 15C has mild cross- reactivity with serotype 15B
Public
Hospitalized adults screened for
eligibility
(n = 5,385)
Enrolled: adults hospitalized with
community acquired pneumonia (CAP)
(n = 3,278)
Analyzed
[All-cause CAP population]
(n = 2,917)
S. pneumoniae detected
[Pneumococcal CAP population]
(n = 352)S. pneumoniae not  detected
[Non -pneumococcal CAP]
(n = 2,565)
S. pneumoniae culture positive
from normally sterile site
[Invasive pneumococcal CAP]
(n = 51)S. pneumoniae detected outside
normally sterile site only
[Non -invasive pneumococcal CAP]
(n = 301)Not enrolled (n =2,107)
Enrolled, not analyzed (n = 361)
•No radiographic evidence of pneumonia (n=235)
•Urine not tested by SSUAD (n = 114)
•Patient withdrew (n = 12)Enrolled Patients
12.1%
pneumococcal
prevalence
85.5%
of pneumococcal pneumonia
was non- invasive
PublicPatient Characteristics: Demographics
Characteristic Pneumonia with
S. pneumoniae detected
(n= 352)Pneumonia without
S. pneumoniae detected
(n= 2565)P-value
Age in years, median (IQR) 60.3 (50.6, 70.2) 60.5 (46.8, 70.2) 0.34
Age category, n (%) 0.01
18-49 years 85 (24.1%) 767/2564 (29.9%)
50-64 years 141 (40.1%) 817/2564 (31.9%)
≥65 years 126 (35.8%) 980/2564 (38.2%)
Female sex assigned at birth, n (%) 167/350 (47.7%) 1147/2558 (44.8%)
Race, n (%) <0.01
White 198 (56.2%) 1771 (69.0%)
Black 145 (41.2%) 703 (27.4%)
Asian 1 (0.3%) 38 (1.5%)
American Indian/Native
Alaskan2 (0.6%) 14 (0.5%)
Native Hawaiian/Pacific Islander2 (0.6%) 6 (0.2%)
Other 6 (1.7%) 54 (2.1%)
Ethnicity, n (%) 0.95
Not Hispanic 328 (93.2%) 2394 (93.3%)
Hispanic 14 (4.0%) 94 (3.7%)
Unknown 10 (2.8%) 77 (3.0%)7
Public
Characteristic Pneumonia with
S. pneumoniae detected
(n= 352)Pneumonia without
S. pneumoniae detected
(n= 2565)P-value
Type of home before illness, n (%) 0.27
Community dwelling 320 (90.9%) 2382 (92.9%)
Nursing Home 6 (1.7%) 43 (1.7%)
Assisted Living 6 (1.7%) 33 (1.3%)
Rehabilitation hospital 1 (0.3%) 13 (0.5%)
School housing 0 (0.0%) 0 (0.0%)
Homeless/shelter 12 (3.4%) 40 (1.6%)
Other 3 (0.9%) 33 (1.3%)
Unknown 4 (1.1%) 21 (0.8%)
Ever regularly smoked tobacco, n (%) 205/349 (58.7%) 1232/2554 (48.2%) <0.01
Alcohol use >3 days/week, n (%) 30/348 (8.6%) 145/2543 (5.7%) 0.03
Use of opioids at least weekly, n (%) 68/339 (20.1%) 438/2462 (17.8%) 0.31
Interacts with child <5 years old at
least once per week, n (%)122/340 (35.9%) 682/2468 (27.6%) <0.01
Lives with children, n (%) 83/346 (24.0%) 517/2534 (20.4%)Patient Characteristics: Social History
8
Public
Characteristic Pneumonia with
S. pneumoniae detected
(n= 352)Pneumonia without
S. pneumoniae detected
(n= 2565)P-value
Chronic medical conditions, n (%)
Dementia 11/349 (3.2%) 65/2528 (2.6%) 0.362
COPD 97/346 (28.0%) 487/2510 (19.4%) <0.001
Asthma 72/346 (20.8%) 474/2518 (18.8%) 0.413
Heart failure 61/340 (17.9%) 446/2509 (17.8%) 0.824
Prior MI 37/344 (10.8%) 231/2525 (9.1%) 0.359
Prior stroke 38/347 (11.0%) 255/2516 (10.1%) 0.651
End stage kidney disease with
chronic kidney replacement14/342 (4.1%) 125/2515 (5.0%) 0.424
Diabetes mellitus 82/348 (23.6%) 684/2525 (27.1%) 0.159
Chronic liver disease 30/343 (8.7%) 173/2508 (6.9%) 0.254
Immunosuppression 72/343 (21.0%) 529/2499 (21.2%) 0.983
Solid organ cancer 80/348 (23.0%) 589/2501 (23.6%) 0.981
Hematologic cancer 30/346 (8.7%) 193/2511 (7.7%) 0.598
Solid organ transplant 25/347 (7.2%) 205/2528 (8.1%) 0.545
Pregnant 0/348 (0.0%) 22/2533 (0.9%) 0.081
Obesity with body mass index
>30 kg/m289/355 (25.9%) 1009/2479 (40.7%) <0.001Patient Characteristics: Chronic Medical Conditions
9
Public
Characteristic Pneumonia with
S. pneumoniae detected
(n= 352)Pneumonia without
S. pneumoniae detected
(n= 2565)P-value
Received antibiotics for current illness before
hospitalization, n (%)71/328 (21.6%) 613/2297 (26.7%) 0.05
Duration of acute illness prior to hospital admission [days], median (IQR)2.6 (1.3, 5.0) 2.7 (1.1, 5.7) 0.36
CURB- 65* score at hospital admission, n (%) 0.17
0 (low risk) 123/345 (35.7%) 943/2523 (37.4%)
1 (low risk) 126/345 (36.5%) 869/2523 (34.4%)
2 (moderate risk) 60/345 (17.4%) 547/2523 (21.7%)
3 (high risk) 31/345 (9.0%) 150/2523 (5.9%)
4 (high risk) 5/345 (1.4%) 14/2523 (0.6%)
5 (high risk) 0/345 (0.0%) 0/2523 (0.0%)
Timing of Enrollment <0.01
Before COVID- 19 in US (October 2018 –
February 2020)231/345 (67.0%) 1249/2519 (49.6%)
After COVID- 19 in US (March 2020 –
October 2022)114/345 (33.0%) 1270/2519 (50.4%)Patient Characteristics: Acute Illness
10* CURB -65: pneumonia severity scoring system, consisting of the following variables: confusion, uremia, respiratory rate, blood pressure, age >65
Public
BinaxNOW
125 patients positive
Cultures
56 patients positive44 53 SSUAD
283 patients positive 199
1117523352 Patients with ≥1 Positive Pneumococcal Test
12Percentage of Pneumococcal Serotype Detections
14.6%
9.8%
7.0%
6.0%5.7%5.4%5.1%4.7%4.1%3.5%3.2%2.8%2.2%1.9%1.6%1.3%0.9% 0.3% 0.0%
n=46 n=31 n=22 n=19 n=18 n=17 n=16 n=15 n=13 n=11 n=10 n=9 n=7 n=6 n=5 n=4 n=3n=1n=0
3 22F 19A 35B 9N 19F 23A 11A 23B 7F, 8,
17F, 316A/C 16F,
20A1, 5 9V, 15C 15A 33F 4, 6B,
24F14, 10A,
12F18C,
23F
Serotype316 serotypes detected by SSUAD (denominator) among 283 unique patients
13Vaccine Category Pneumococcal serotypes% of serotypes in adults
hospitalized with CAP
(n=2917)
V116 (21 serotypes) 3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 15A, 15C, 16F, 17F, 19A, 20A, 22F, 23A, 23B, 24F, 31, 33F, 35B 9.3%
PCV20  (19 serotypes; serotype 15B not tested) 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 18C, 19A, 19F, 22F, 23F, 33F 6.7%
PCV15  (15 serotypes) 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, 33F 5.8%
V116 and not PCV15 or PCV20 (11 serotypes) 9N, 15A, 15C, 16F, 17F, 20A, 23A, 23B, 24F, 31, 35B 4.1%8.0%11.3%
8.7%
4.7%8.4%
6.9%
4.0%7.3%
5.8%
4.0%4.8%
3.1%
0%2%4%6%8%10%12%
18-49 years old (n=852) 50-64 years old (n=958) 65+ years old (n=1107)% of patients with ≥1 serotype in categoryV116 PCV20 PCV15 11 unique V116 serotypesPercentage of Pneumococcal Serotype by Vaccine in Adults Hospitalized with CAP
Public
Conclusions
•Pneumococcal CAP remains a major cause of adult hospitalizations
•SSUAD assays greatly increase S. pneumoniae detection over traditional testing
•Among adults hospitalized with CAP:
•12.1% with S. pneumoniae detected
•9.3% with a pneumococcal serotype in V116
•4.1% with a serotype unique to V116 (not PCV15 or PCV20)
•Most commonly detected serotypes unique to V116: 35B, 9N, 23A, 23B
14

Summary: Public Interim Results from the PNEUMO Study .  Pneumococcal pNeumonia Epidemiology, Urine serotyping, and  Mental Outcomes study February 29, 2024 Study Leadership Wesley H. Self, MD Vanderbilt UniversityJ. Jackson Resser , MS Vanderbilt UniversityKelly D. Johnson, PhDMerck & Co., Inc. 1 Funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USANadine Rouphael , MD Emory University Public PNEUMO study overview •Adults 18+ years hospitalized with  community acquired…


03 Rabies Rao 508

National Center for Emerging and Zoonotic Infectious Diseases
Summary of Evidence to Recommendations
Framework for Rabies Pre -Exposure Prophylaxis Vote
Advisory Committee on Immunization Practices
February 24, 2021Agam Rao, MD
CAPT, US Public Health Service
Poxvirus and Rabies Branch
Centers for Disease Control and Prevention
Rabies antibody response
▪Target response, i.e., ≥ minimum antibody titer, 0.5 IU/mL, regardless of
series
–Children
–Pregnant women
–Persons ≥ 65 years of age
▪Persons with altered immunity
–Efficacy can be a concern
–Titer check after primary series (and boosters until ≥ 0.5 IU/mL)
Rabies vaccines licensed in U.S.
▪Been used in the U.S. for decades
▪No change in favorable safety profileBiologicProduct
nameManufacturer Administration Potency
Human
diploid cell
vaccine
(HDCV)Imovax Sanofi Pasteur intramuscularly≥2.5 IU of
rabies
antigen
Purified
chick
embryo cell
vaccine
(PCECV)RabAvertBavarian
Nordicintramuscularly≥2.5 IU of
rabies
antigen
Estimated* PrEP use in the United States
▪Doses:  170,000 including 500 booster doses
▪Categories of people receiving PrEP :  60,535 / year
–Travelers and “other risk groups”: 41,117
–Veterinary technicians:  13,860
–Veterinary students:  3,500
–Animal control: 1,178
–Rabies laboratory personnel: 480
–Wildlife biologists:  400* Mathematical model based on
workforce statistics produced by
Bureau of Labor Statistics and market
research provided by Bavarian Nordic
Adherence to ACIP PrEP recommendations*
▪Veterinary students:  100% (required for clinics)
▪Laboratory personnel:  100% (required)
▪Animal control:  78.5%
▪Veterinary technicians/staff:  69.3% (in other published studies, 30 -40% adherence)
▪Wildlife biologists:  ~50%
▪Other risk groups:  ?
▪Travelers:  ?
*Some results from unpublished CDC data; Blanton
et al.
Includes data obtained from ~2,000 persons
Survey sent to members of professional
organizations who were certified providers and
were likely more compliant with the ACIP recs
than persons not captured by the survey
EtRfor policy question #1:  Primary
immunogenicity
PrEP policy question #1
Policy question: Should a two dose pre -exposure prophylaxis ( PrEP ) series
involving HDCV* or PCECV †IM [0, 7 days] replace the 3 dose series IM[0, 7,
21/28 days] for all those for whom rabies vaccine PreP is recommended?
Population Persons for whom rabies vaccine PrEP is recommended
Intervention [0, 7 days] rabies vaccine PrEP schedule
Comparison [0, 7, 21/28 days] rabies vaccine PrEP schedule
Outcome Primary immunogenicity
*Human diploid cell vaccine
† Purified chick embryo cell vaccine
Problem: Rabies and PrEP
▪Rabies is nearly always fatal
▪PrEP is important component of preventing human rabies in U.S.
▪PrEP critically important to some persons
–Unusual exposures (e.g., aerosolized) or high concentration virus
–Unrecognized exposures
–Frequent exposure to potentially rabid animals
–Travel abroad to canine -rabies endemic regions without quick PEP access
Primary immunogenicity of PrEP for rabies
▪Rabies modern cell culture vaccines are effective
▪ACIP has recommended PrEP for decades
▪Noncompliance among some for whom it is recommended
–Out-of-pocket costs
–Some occupations do not require it
–Insufficient time to complete 3 -dose series before international travel
EtR:  Policy question #1
Domains WG interpretation
Benefits:  How substantial are the desired
anticipated effectsMinimal; 100% of people seroconvert for proposed and
for previous schedule
Harms:  How substantial are undesirable
anticipated effects?Minimal; No expected safety concerns
Benefit / Harm:  Do desirable effects outweigh
undesirable effects?Favors both
Overall certainty for evidence:  effectiveness Moderate certainty of evidence (Level 2) due to
concerns for risk of bias
PrEP costs
▪Reimbursement price for vaccine
dose:  $331*(Source: CMS/ASP)
▪Additional costs are variable
depending on location PrEP is
administered
▪We estimate $1100 -$3500 for
PrEP series
(3 vaccines + additional costs)
Figure: Location of pre -exposure vaccine administration by occupation
in the United States; not shown is PrEP received in Emergency
Departments which was the location for PrEP in 2% of respondents
(Source:  Blanton et al, unpublished data from CDC survey)
Proportion of PrEP costs that are out -of-pocket
Vaccination indication # reporting
insurance would
cover at least part
of cost
Booster       Titer#  reporting
employer would
cover at least
part of cost
Booster       Titer# reporting
EITHER would
cover at least part
of the cost
Booster      Titer
Veterinary professionals 25% 25% 20% 40% 25% 30%
Animal control 50% 40% 54% 20% 60% 60%
Animal rehabilitationists 25% 33% 12% 20% 25% 40%
Source:  Unpublished CDC data; Blanton et al
EtR:  Policy question #1
Domains WG interpretation
Target population sentiments:  uncertainty about
or variability in how much people value outcomes?No:  Target population values “protection” from rabies
and there is likely no important variability
Acceptability to stakeholders? Yes:  Shorter schedule preferred by patients & providers
Reasonable and efficient allocation of resources? Yes:  Cost savings and because rabies vaccine shortages
have occurred in U.S.
Impact on equity? Probably reduced because of decreased costs
Feasible to implement? Yes: Shorter series than current series
EtR:  Policy question #1
Domains WG interpretation
Target population sentiments:  Does the target
population feel desirable effects are large relative
to undesirable effectsProbably yes
•Data supports high costs incurred by PrEP
recipients
•Persons who should receive PrEP for travel are
known to not receive it because <21 days from
clinic appointment to travel
Balance of Consequences
Undesirable                                        Undesirable Balance between
consequences clearly                       consequences probably               desirable and undesirable
outweigh desirable                           outweigh desirable                       consequences is closely
consequences in most                      consequences in most                 balanced or uncertain
settings settings
Desirable consequences Desirable consequences             There is insufficient evidence
probably outweigh clearly outweigh                           to determine the balance of
undesirable consequences undesirable consequences          consequences
inmost settings in most settingsX
Proposed recommendation for vote
ACIP recommends a 2 -dose [0, 7 days] intramuscular
rabies vaccine series in immunocompetant persons
>= 18 years of age for whom rabies vaccine pre -
exposure prophylaxis ( PrEP ) is indicatedRecommendation
EtRfor policy question #2: Long -term
immunogenicity
PrEP policy question #2
Policy question: Should an IM booster dose of rabies vaccine (*PCECV or
†HDCV) be recommended as an alternative to a titer check no sooner than
day 21 and no later than 3 years after the two dose pre -exposure prophylaxis
(PrEP ) series IM [0, 7 days] for those in the #3 risk category of people who
receive PreP ?
PopulationPersons in the #3 risk category for whom rabies vaccine PrEP is
recommended
InterventionDay 21 -year 3 rabies vaccine booster after [0, 7 days] rabies
vaccine PrEP schedule
ComparisonNo rabies vaccine booster after [0, 7 days] rabies vaccine PrEP
schedule
Outcome Long -term immunogenicity
*Human diploid cell vaccine
† Purified chick embryo cell vaccine
Problem: Long -term immunogenicity for rabies
▪Immunology suggests that anamnestic response to an exposure occurs
▪WHO approved 2 -dose series (no booster or titers)
▪Rabies is nearly 100% fatal
▪WG opted for most cautious route to ensure long -term immunogenicity for [0, 7
days] series
–Strong data for long -term immunogenicity only exists for up to 3 years
–Data shows that titer at ≥ 1 year, is marker of long -term immunogenicity
–WG proposed titer at 1 -3 years (and boost accordingly) OR
–Booster no sooner than day 21 and no later than year 3
Long -term immunogenicity reported in recently
published article*
▪6 persons who received [0, 7 days] IM series, were evaluated after 10 -11
years
–3 male; 3 female
–Ages 34 -46
–5 had titers ≥ 0.5 IU/mL
–All had 4 -fold increase in titers after booster
▪More data expected about long -term immunogenicity of 2 -dose series because
WHO recommendations made in 2018
*De Pijper et al, Long -term memory response after a single intramuscular rabies booster vaccination, 10 -24
years after primary vaccination. Journal of Infectious Diseases.  Epub January 2021
EtR:  Policy question #2
Domains WG interpretation
Benefits:  How substantial are the desired
anticipated effectsModerate
•Booster at day 21 is equivalent to current 3 -dose
series and is known to provide long -term
immunogenicity
•100% of subjects mounted anamnestic response to
booster at 1 -3 years
Harms:  How substantial are undesirable
anticipated effects?Minimal; No expected safety concerns
Benefit / Harm:  Do desirable effects outweigh
undesirable effects?Favors intervention
Overall certainty for evidence:  effectiveness Low certainty of evidence (Level 3)
EtR:  Policy question #2
Domain WG interpretation
Target population sentiments:  Does the target
population feel desirable effects are large relative
to undesirable effectsProbably yes
•Stakeholders want to avoid acquiring high -stakes
infection
•Booster provides reassurance that outweighs any
inconvenience
Target population sentiments:  uncertainty about
or variability in how much people value outcomes?No:  Target population values “protection” from rabies
and there is likely no important variability
Acceptability to stakeholders? Yes:  Stakeholders accustomed to accommodating third
dose of rabies vaccine and will find it acceptable to
have booster as an option
Reasonable and efficient allocation of resources? Yes:  Cost savings
Costs of titer compared to booster
▪Titer:  Cost ~$50 -$75* + cost of blood draw / clinic appointment
▪Booster:  ~$331 for cost of booster + additional costs
*KSU website and word of mouth
EtR:  Policy question #2
Domains WG interpretation
Impact on equity? Don’t know:  some PrEP costs are out -of-pocket;
because titer is offered as option, inequity could be
resolved by choosing that option
Feasible to implement? Yes: Administrators could opt to schedule booster dose
at the time of primary vaccination
Balance of Consequences
Undesirable                                        Undesirable Balance between
consequences clearly                       consequences probably               desirable and undesirable
outweigh desirable                           outweigh desirable                       consequences is closely
consequences in most                      consequences in most                 balanced or uncertain
settings settings
Desirable consequences                   Desirable consequences             There is insufficient evidence
probably outweigh                             clearly outweigh                           to determine the balance of
undesirable consequences               undesirable consequences          consequences
in most settings                                  in most settings

Proposed recommendation for vote
ACIP recommends an intramuscular booster dose of rabies
vaccine, as an alternative to a titer check, for
immunocompetent persons >=18 years who have sustained and
elevated risk for only recognized rabies exposures (i.e., those in
risk category #3 of rabies PrEP recommendations table).  The
booster dose should be administered no sooner than day 21
but no later than 3 years after the 2 -dose PrEP series. Recommendation
Clinical guidance scenarios
Time (in years)Days [0, 7 days]2-dose PrEP
Year 3Rabies
exposure
To be cautious:
PEP = RIG + vaccine IM[0, 3, 7, 14 days]No titer or
booster
Clinical guidance scenarios
Time (in years)Days [0, 7 days] 2-dose PrEP
Year 3Traveling againNo titer or
boosterThese situations currently are handled
on case -by-case basis
Acknowledgements
▪Rabies WG
▪Ryan Wallace
▪Jesse Blanton
▪Doug Campos -Outcalt
▪Rebecca Morgan
▪Florence Whitehill
▪Jessica MacNeil
▪Whitni Davidson
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.
National Center for Emerging and Zoonotic Infectious Diseases
Division of High -Consequence Pathogens and PathologyQuestions?
Implications of proposed changes
Risk
groupPopulation Primary
immunog
enicityImplications Long -term
immunogenicityImplications
#1 Research laboratorians
Diagnostic laboratorians
#2 Bat biologists
#3Animal care professionals in
terrestrial rabies regions
Animal care professionals in
non -terrestrial rabies regions,
students, spelunkers,
persistent travelers
Short -term animal care
professionals and persons
without sustained risk for
rabiesTiter every 6 months
IM [0, 7
days]Fewer vaccine doses
but equivalent
efficacyMakes sense to
consider all
laboratorians equallyTiter check ever 6
months1
Titer check every 2
years2No change
No change
Fewer vaccine doses
and/or  fewer titer checks
Same number of vaccine
doses OR instead of 3rd
vaccine, a titer
No additional vaccine
and no titersTiter once (1 -3
years after
primary series)
OR
Booster no sooner
than day 21 and no
later than year 3
PrEP Policy Question #1
Table 3a: Summary of Randomized Control Trial Studies Reporting Outcome
Authors last
name, pub
yearAge (years) N
interventionN
comparisonVaccine Risk Ratio
[95% CI]Study limitations
(Risk of Bias)
Endy , 2019 Mean 32.4,
Range 18 -5922 24 PCEC, IM, ID 1.00
[0.89, 1.12]Some concerns1
Soentjens ,
2019Median 29.0,
Range NR242 240 HDCV, ID 1.00
[0.99, 1.01]Some concerns2
1Allocation concealment not reported. Study did not blind participants or healthcare personnel; however, unlikely that co -interve ntions would
have influenced the outcome.
2Method of randomization and allocation not reported. Study did not blind participants or healthcare personnel; however, unlik elythat co -
interventions would have influenced the outcome .
PrEP Policy Question #1
Table 3b: Summary of Observational Studies Reporting Outcome
Authors last name, pub
yearAge (years) N
interventionN
comparisonVaccine Risk Ratio [95%
CI]1Study limitations (Study
quality2)
Ajjan , 1989 Mean 22, Range 19 -41 72 69 HDCV, IM 1.00 [0.97, 1.03] 9/9 No concerns
Arora, 2004 Mean 26.2, NR 44 44 HDCV, IM 1.00 [0.96, 1.04] 9/9 No concerns
Briggs, 1996 NR 146 146 HDCV, IM 1.00 [0.99, 1.01] 9/9 No concerns
Cramer 2016 Mean 36.7, SD 12.9 371 364 PCEC, IM 0.99 [0.98,
1.01]47/9 Minimal concerns
Hacibektasoglu , 1992 Mean 20, Range 18 -24 30 30 HDCV, IM 0.90 [0.79, 1.03] 9/9 No concerns
Jaijaroensup, 1999 NR, Range 17 -22 138 129 PCEC, IM, ID 0.94 [0.87,
1.02]49/9 No concerns
Kitala, 1990 NR 37 37 HDCV, IM 1.00 [0.95, 1.05] 8/9 Minimal concerns
Recuenco, 2017 Median 41.0, Range 20 -
6260 59 PCEC, IM, ID 1.00 [0.96, 1.05]49/9 No concerns
Sabchareon, 1999 Mean 10,
SD 1.33190 190 HDCV, IM 1.00 [0.99, 1.01] 7/9 Minimal concerns
Vodopija , 1986 NR 49 46 HDCV, PCEC,
IM1.00 [0.94, 1.06]49/9 No concerns
1Data from observational studies, where intervention and comparison data were taken from the same people at different time poi nts, were analyzed using M -H Risk Ratio
random effects procedure.  Due to unavailable raw data on pairing, a matched analysis was not possible.
2Study quality for observational studies was assessed using the Newcastle Ottawa Scale.
3Age for total study population was not reported in this paper. Numbers in this cell are from the study arm from which data we re extracted.
4Studies contained multiple arms relative to the analysis. Risk ratio reflects pooled analysis from eligible arms.
PrEP Policy Question #2
Table 3: Summary of Studies Reporting Outcome
Authors
last name,
pub yearAge (years) N intervention N comparison Comparator
vaccineRisk Ratio
[95% CI]Study limitations (Study
quality3)
Endy , 2019 Mean 32.4,
Range 18 -5920 No comparison1PCEC, IM Not able to
calculate28/9 Minimal concerns
Soentjens ,
2019Median 29.0, NR 183 No comparison1 HDCV, IM Not able to
calculate28/9 Minimal concerns
1No comparison data available for this policy question available in these studies.
2No comparison data available to calculate effect estimate.
3Study quality for observational studies was assessed using the Newcastle Ottawa Scale.
Reminder: proposed changes
Highlighted:  Proposed
changes to 2008 ACIP
recommendations
Red box:   Today’s votes Primary
immunogenicity Long -term
immunogenicity
#1 risk group
(i.e., laboratorians) IM [0, 7 days] Titers every 6 months
after primary series
#2 risk group
(i.e., persons who
handle bats or enter
high density bat
environments)IM [0, 7 days] Titers every 2 years after
primary series
#3 risk group (i.e.,
veterinarians, vet
assistants, animal
handlers, vet students,
travelers etc.)IM [0, 7 days]Titer once at 2 years after
primary series
OR
Booster once no sooner
than day 21 and no later
than 3 yearsȽ

Summary: National Center for Emerging and Zoonotic Infectious Diseases Summary of Evidence to Recommendations  Framework for Rabies Pre -Exposure Prophylaxis Vote Advisory Committee on Immunization Practices February 24, 2021Agam Rao, MD CAPT, US Public Health Service Poxvirus and Rabies Branch Centers for Disease Control and Prevention Rabies antibody response ▪Target response, i.e., ≥ minimum antibody titer, 0.5 IU/mL, regardless of  series –Children –Pregnant women –Persons ≥ 65 years of age…


01 Loehr influenza 508

National Center for Immunization & Respiratory Diseases
Influenza Work Group— Introduction
Dr. Jamie Loehr (Work Group Chair)
Advisory Committee on Immunization Practices
April 15, 2025
Influenza Work Group
ACIP Members
•Jamie Loehr (Chair)
•Robert Schechter
•Albert Shaw
•Keipp Talbot
Ex Officio
•Timothy Brennan (FDA)
•Uzo Chukwuma (IHS)
•Walter Greenhalgh (HRSA)
•Michael Ison (NIH)
•Cynthia Nolletti (FDA)
•Jo Resnick (FDA)
•Chris Roberts (NIH)Liaison Representatives and
Consultants
•Robert Atmar
•Kevin Ault
•Ed Belongia
•Hank Bernstein
•Kris Bryant
•Sarah Coles
•Sandra Fryhofer
•Robert Hopkins
•Wendy Keitel
•Camille Kotton
•Krissy Moehling•Zackary Moore
•Flor Munoz
•Caitlin Newhouse
•Jesse Papenburg
•William Schaffner
•Ken Schmader
•Tamara Sheffield
•Angela Sinilaite
•Peter Szilagyi
•Matthew Zahn
CDC Lead
•Lisa Grohskopf
2
CDC Participants
•Lenee Blanton
•Karen Broder
•Alicia Budd
•Kayla Calhoun
•Jessie Chung
•Jennifer DeCuir
•Sascha Ellington
•Tarayn Fairlie
•Jill Ferdinands
•Brendan Flannery
•Andrew Kroger
•Samantha Olson
•David Shay
•Tom Shimabukuro
•Naomi Tepper
3
Influenza Vaccine Composition for 2025 -26
• On March 15, 2025, the U. S. Food and Drug Administration made recommendations for the
composition of U.S. -licensed influenza vaccines for the 2025- 26 influenza season.
• The 2025- 26 vaccine composition includes an update to the influenza A(H3N2 ) component.
-For egg -based vaccines:
›an A/Victoria/4897/2022 (H1N1)pdm09-like virus;
›an A/Croatia/10136RV/2023 (H3N2) -like virus; and
›a B/Austria/1359417/2021 (B/Victoria lineage) -like virus
-For cell culture and recombinant vaccines:
›an A/Wisconsin/67/2022 (H1N1)pdm09-like virus;
›an A/District of Columbia/27/2023 (H3N2) -like virus; and
›a B/Austria/1359417/2021 (B/Victoria lineage) -like virus
4https://www.fda.gov/vaccines -blood -biologics/influenza -vaccine -composition -2025 -2026 -us-influenza- season
Influenza Vaccine Effectiveness (VE) Estimates
Updates:
• Interim Estimates of 2024 –25 Seasonal Influenza Vaccine Effectiveness
⁻Dr. Aaron Frutos (CDC/NCIRD/ID)
• Interim Influenza Vaccine Effectiveness Against Laboratory -Confirmed Influenza , California ,
October 2024— January 2025
⁻Dr. Sophie Zhu (California Department of Public Health and CDC/PHIC) and Dr. Joshua Quint
(California Department of Public Health)Issue:
• Influenza vaccine effectiveness varies and is assessed annually through several CDC platforms
focusing on laboratory- confirmed influenza outpatient visits and hospitalizations in adult and
pediatric populations.
• VE estimates are presented to the ACIP as they become available.
• Preliminary 2024 -25  VE estimates are available from CDC platforms and from the California
Department of Public Health.
5
FluMist (LAIV3) Self -/Caregiver Administration
Updates:
•FluMist Self/Caregiver Administration
⁻Dr. Allyn Bandell, AstraZenecaIssue:
•On September 20, 2024, FDA approved FluMist for self or caregiver administration.
•This program is expected to be available for the 2025 -26 influenza season.
6
Upcoming Votes
7•Vote concerning updates to the 2025-26 ACIP influenza statement is
expected at the June 2025 ACIP meeting.
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 Work Group— Introduction Dr. Jamie Loehr (Work Group Chair) Advisory Committee on Immunization Practices April 15, 2025 Influenza Work Group ACIP Members •Jamie Loehr (Chair) •Robert Schechter •Albert Shaw •Keipp Talbot Ex Officio •Timothy Brennan (FDA) •Uzo Chukwuma (IHS) •Walter Greenhalgh (HRSA) •Michael Ison (NIH) •Cynthia Nolletti (FDA) •Jo Resnick (FDA) •Chris Roberts (NIH)Liaison Representatives and  Consultants •Robert…


02 Frutos influenza 508

Interim Estimates of 2024 –25 Seasonal Influenza
Vaccine Effectiveness
Aaron M. Frutos, PhD, MPH
On behalf of CDC Influenza Vaccine Effectiveness CollaboratorsNational Center for Immunization & Respiratory Diseases

CDC Influenza Vaccine Effectiveness
Networks
Four networks to evaluate vaccine effectiveness (VE) against laboratory -
confirmed influenza for children and adolescents and adults in the
outpatient and inpatient settings
•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)CDC Influenza Vaccine Effectiveness Networks
3
VISION
IVYNVSNThese networks include all ages across settings
AgeSettingOutpatient
clinic
HospitalizationEmergency
department/
urgent careUS Flu VE
Adults
(≥18 years)Children and adolescents
(6 months – 17 years)
4
NVSNNVSN: all settings
AgeSettingOutpatient
clinic
HospitalizationEmergency
department/
urgent care
Adults
(≥18 years)Children and adolescents
(6 months – 17 years)
5
NVSNUS Flu VE: Outpatient clinic and ED/UC
US Flu VE
AgeSettingOutpatient
clinic
HospitalizationEmergency
department/
urgent care
Adults
(≥18 years)Children and adolescents
(6 months – 17 years)
6
NVSNVISION: ED/UC & hospitalization
US Flu VE
VISION
AgeSettingOutpatient
clinic
HospitalizationEmergency
department/
urgent care
Adults
(≥18 years)Children and adolescents
(6 months – 17 years)
7
IVYIVY: hospitalization
AgeSettingOutpatient
clinic
HospitalizationEmergency
department/
urgent care
Adults
(≥18 years)Children and adolescents
(6 months – 17 years)
8
IVYUS Flu VE: Outpatient clinic and ED/UC
US Flu VE
AgeSettingOutpatient
clinic
HospitalizationEmergency
department/
urgent care
Adults
(≥18 years)Children and adolescents
(6 months – 17 years)
9
IVYVISION: ED/UC & hospitalization
US Flu VE
VISION
AgeSettingOutpatient
clinic
HospitalizationEmergency
department/
urgent care
Adults
(≥18 years)Children and adolescents
(6 months – 17 years)
10
These networks include all ages across settings
Outpatient
VISION
IVYNVSN
AgeSettingOutpatient
clinic
HospitalizationEmergency
department/
urgent careUS Flu VE
Adults
(≥18 years)Children and adolescents
(6 months – 17 years)
11
CDC influenza VE networks include patients from 23
states
12
•Enrollees: Received medical care for an acute respiratory illness
•Dates of enrollment: Fall 2024 – Early 2025
•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 2024 –25 seasonal flu vaccine according to medical
records, immunization registries, claims data, and/or self -report2024 –2025 Influenza VE Methods
13
•Analysis : VE = (1 – adjusted OR) x 100%
–Adjusted for geographic region, age, calendar time of illness
»US Flu VE, and VISION also adjusted for sex and race and ethnicity
–VE estimates were calculated for influenza A subtypes A(H1N1)pdm09 and A(H3N2)
when possible
»Influenza A subtype estimates were not calculated for VISION because of
limited subtype data
–VE was not estimated for some age groups and settings when sample size was small or
when models did not converge2024 –2025 Influenza VE Methods
14
Influenza A subtype by network
Influenza A subtype by network
Influenza A subtype by network, total (%)
Influenza A(H1N1)pdm09 Influenza A(H3N2)
IVY 50 (31) 110 (69)
NVSN 284 (52) 262 (48)
US Flu VE 168 (33) 337 (67)
16
Pediatric VE
(aged 6 months –17 years)
Pediatric VE against any influenza
Influenza test result by influenza vaccination
status, no. vaccinated/Total (%)
Influenza -positive Influenza -negative VE (95% CI)
NVSN (Outpatient) 100/482 (21) 855/2,487 (34) 59 (47 –68)
US Flu VE (Outpatient) 54/217 (25) 256/917 (28) 32 (1 –54)
VISION (Outpatient) 1,322/9,563 (14) 5,943/27,356 (22) 60 (56 –63)
NVSN (Inpatient) 28/119 (24) 613/1,523 (40) 63 (41 –76)
VISION (Inpatient) 16/157 (10) 406/1,481 (27) 78 (60 –89)
18
Pediatric VE against any influenza
19
Pediatric VE against influenza A(H1N1)pdm09
20
Pediatric VE against influenza A(H3N2)
21
Adult VE
(aged ≥18 years)
Adult 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) 112/475 (24) 592/1,735 (34) 34 (16 –51)
VISION (Outpatient) 5,631/26,011 (22) 25,842/76,628 (34) 54 (52 –56)
IVY (Inpatient) 211/675 (31) 873/2,500 (35) 41 (28 –52)
VISION (Inpatient) 905/2,959 (31) 10,869/28,074 (39) 55 (51 –59)
23
Adult VE against any influenza
24
Adult VE against influenza A(H1N1)pdm09
25
Adult VE against influenza A(H3N2)
26
Adult (aged ≥65) VE
Adult (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) 28/56 (50) 195/332 (59) 18 (-69–60)
VISION (Outpatient) 2,575/5,731 (45) 14,978/27,525 (54) 51 (47 –54)
IVY (Inpatient) 150/341 (44) 591/1,313 (45) 38 (19 –52)
VISION (Inpatient) 693/1,897 (37) 8,903/19,271 (46) 57 (52 –61)
28
Adult (aged ≥65) VE against any influenza
29
Discussion
•Vaccination with a 2024 –25 influenza vaccine reduced the risk  for
medically attended influenza outpatient visits and hospitalizations  among
children and adolescents and adults across 23 US states
•Influenza v accination was effective against influenza A viruses  with
variation by subtype across networks
•Interim Estimates of 2024 –2025 Seasonal Influenza Vaccine Effectiveness —
Four Vaccine Effectiveness Networks, United States, October 2024 –
February 2025 | MMWRSummary of four CDC influenza VE networks
31
For more information, contact CDC
1-800-CDC-INFO (232 -4636)
TTY:  1 -888-232-6348    www.cdc.gov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official
position of the Centers for Disease Control and Prevention.
Thank you
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
VISION
Adult (aged 18 –64) VE
Adult (aged 18 –64) 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) 84/419 (20) 397/1,403 (28) 37 (15 –53)
VISION (Outpatient) 3,056/20,280 (15) 10,864/49,103 (22) 56 (53 –58)
IVY (Inpatient) 61/334 (18) 282/1187 (24) 48 (28 –63)
VISION (Inpatient) 212/1,062 (20) 1,966/8,803 (22) 51 (41 –59)
34
Adult (aged 18 –64) VE against any influenza
35
Pediatric VE Tables
Pediatric VE against Influenza A(H1N1)pdm09
Influenza test result by influenza vaccination
status, no. vaccinated/Total (%)
Influenza -positive Influenza -negative VE (95% CI)
NVSN (Outpatient) 32/224 (14) 855/2,487 (34) 72 (59 –81)
US Flu VE (Outpatient) 9/50 (18) 256/917 (28) 53 (3 –79)
NVSN (Inpatient) 13/60 (22) 613/1,523 (40) 63 (30 –81)
37
Pediatric VE against Influenza A(H3N2)
Influenza test result by influenza vaccination
status, no. vaccinated/Total (%)
Influenza -positive Influenza -negative VE (95% CI)
NVSN (Outpatient) 62/218 (28) 855/2,487 (34) 42 (19 –58)
US Flu VE (Outpatient) 29/107 (27) 256/917 (28) 16 (-34–49)
NVSN (Inpatient) 12/44 (27) 613/1,523 (40) 55 (14 –77)
38
Adult VE Tables
(aged ≥18 years)
Adult VE against Influenza A(H1N1)pdm09
Influenza test result by influenza vaccination
status, no. vaccinated/Total (%)
Influenza -positive Influenza -negative VE (95% CI)
US Flu VE (Outpatient) 36/118 (31) 592/1,735 (34) 42 (8 –64)
IVY (Inpatient) 12/50 (24) 873/2,500 (35) 39 (-14–67)
40
Adult VE against Influenza A(H3N2)
Influenza test result by influenza vaccination
status, no. vaccinated/Total (%)
Influenza -positive Influenza -negative VE (95% CI)
US Flu VE (Outpatient) 56/230 (24) 592/1,735 (34) 25 (-6–48)
IVY (Inpatient) 8/110 (26) 873/2,500 (35) 51 (22 –69)
41

Summary: Interim Estimates of 2024 –25 Seasonal Influenza  Vaccine Effectiveness Aaron M. Frutos, PhD, MPH On behalf of CDC Influenza Vaccine Effectiveness CollaboratorsNational Center for Immunization & Respiratory Diseases  CDC Influenza Vaccine Effectiveness  Networks Four networks to evaluate vaccine effectiveness (VE) against laboratory - confirmed influenza for children and adolescents and adults in the  outpatient and inpatient settings  •Investigating Respiratory Viruses in the Acutely Ill…


03 zhu influenza 508

Confidential -Low
Interim Influenza Vaccine
Effectiveness Against Laboratory -
Confirmed Influenza, California,
October 2024 –January 2025
Sophie Zhu, PhD and Joshua Quint, PhD
California Department of Public Health
Advisory Committee on Immunization Practices Meeting
April 15, 2025
Confidential -Low
Influenza VEData Type :
Electronic records
Patient interviewsData Sources :
Hospital networks
Public health surveillance
Population :
Pediatric
AdultSetting :
Inpatient
Outpatient
Considerations for calculating vaccine effectiveness
Confidential - Low
Influenza VEData Type :
Electronic records
Patient interviewsData Sources :
Hospital networks
Public health surveillance
Population :
Pediatric
AdultSetting :
Inpatient
Outpatient
Considerations for calculating vaccine effectiveness
Confidential - Low
•January 1, 2023
•All vaccination records  must be
reported to the California Immunization
Registry (CAIR)
•Previously, only certain types of providers
were required to report
•June 15,  2023:
•All influenza test results  must be
reported to California Reportable Disease
Information Exchange (CalREDIE)
•Previously, only positive results were
reported
New California Data Reporting Requirements
Confidential - Low

Confidential - Low
Pediatric : 6 mo–18 yrs
2023–2024 CA estimates similar to  other VE platforms
Confidential - Low
Methods
Confidential - Low
•Dates: October 1, 2024 - January 31, 2025
•Eligibility/inclusion criteria: California residents aged ≥6 months with a test result reported
through the state electronic laboratory reporting (ELR) system
•Outcome (test result): molecular (NAAT) or culture test results for influenza (A/B)
•Exposure (vaccination status): documented dose of seasonal influenza vaccine at least 14
days prior to test date
•Exclusions: duplicate test results for persons with multiple records, laboratories with greater
than 50% weekly positive results
•Analysis:  VE = (1 – adjusted OR) x 100%
•Mixed -effects logistic regression model
•Adjusted for continuous age (natural cubic spline), categorical race and ethnicity; testing
week and county as random effectsCase control study (unmatched)
Confidential - Low
Number of positive influenza detections by laboratories
2024 -2025 season to date
Flu Type
Confidential - Low
•About 5% of influenza positive tests
are subtyped, mostly from public
health laboratories
•Influenza A
•53% A(H3)
•43% A(H1)
•4% A not subtyped
•Only ~300 influenza B samples
lineage typed this season
•Persons with severe disease may be
more likely to have results subtyped
Influenza subtyping
Confidential - Low
Total
N = 591,321
Influenza Positive
22.8%
Vaccinated
17.6%Not Vaccinated
82.4%Influenza Negative
77.2%
Vaccinated
25.9%Not Vaccinated
74.1%Study Population
Test Positivity and Vaccination Status
Confidential - Low
Test Negative Test Positive
Total No. 456,437 134,884
Median Age
       25th percentile
       75th percentile43 yrs
20 yrs
67 yrs30 yrs
11 yrs
55 yrs
Ethnicity - Hispanic or Latino 24% 29%
Race
White
Unknown
Other
Asian
Black
NHPI, AI/AN, or Multiple46%
20%
19%
8%
6%
<1%*39%
22%
23%
8%
6%
<1%*
NHPI = Native Hawaiian or Pacific Islander; AI/AN = American Indian or Alaska Native; * <1% each Study Population
Demographics
Confidential - Low
•Age group by Type (A/B)
•Influenza A subtype (H1N1/H3N2)
•Mode of administration (LAIV/non -LAIV)
•Weekly cumulative
•Month -specific by Type (A/B)Vaccine effectiveness estimates
Confidential - Low
43.7 45.6Vaccine effectiveness by age group
California 2024 –2025
VE (%)
Confidential - Low
VE (%)
Vaccine effectiveness by type and age group
California 2024 –2025
Confidential - Low
Vaccine effectiveness by influenza A subtype
California 2024 –2025

Confidential - Low
Year Vaccine Type VE (95% CI) Count Median Age (IQR)
2024 LAIV 61 (51, 69) 455 7.3 (4.9 –10.4)
2024 Not LAIV 48 (46, 50) 21,980 7.8 (4.4 –12.4)
2023 LAIV 45 (35, 54) 1,387 7.9 (5.3 –10.9)
2023 Not LAIV 52 (51, 54) 66,088 7.3 (4.2 –11.9)Live Attenuated Influenza Vaccine (LAIV)
estimates among children ages 2 –17
Confidential - Low
Positive
Test
Results
VE (%)Cumulative Influenza vaccine effectiveness
California 2024 –2025
Confidential - Low
October November December JanuaryVE (%)Vaccine effectiveness by month  of influenza test
California 2024 –2025
Confidential - Low
October November December JanuaryVaccine effectiveness by month  and type
California 2024 –2025VE (%)
Confidential - Low
Limitations
1.Incomplete documentation and reporting of vaccination and testing
2.Inability to 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.Incomplete and potentially biased reporting for influenza subtypes
5.Lack of control for other confounders (health seeking behavior, pre -existing
conditions)
Confidential - Low
Summary
1.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)
2.Expanded and improved public health data can be leveraged to
calculate timely in -season influenza effectiveness
•Useful to promote additional prevention measures prior to peak
•Prepare for increased hospital capacity
Confidential - Low
Acknowledgements
California Local Health Departments
CDPH Division of Communicable
Disease Control
•Tomás León
•Monica Sun
•Nancy J. Li
•Cynthia Yen
•Cora Hoover
•Robert Schechter
•Seema Jain
•Erin L. MurrayNCIRD Influenza Division
•Brendan Flannery
•Mark Tenforde
•Sascha Ellington
•Jessie Chung

Summary: Confidential -Low Interim Influenza Vaccine  Effectiveness Against Laboratory - Confirmed Influenza, California,  October 2024 –January 2025 Sophie Zhu, PhD and Joshua Quint, PhD California Department of Public Health Advisory Committee on Immunization Practices Meeting April 15, 2025 Confidential -Low Influenza VEData Type :  Electronic records  Patient interviewsData Sources :  Hospital networks Public health surveillance Population : Pediatric AdultSetting : Inpatient Outpatient…