06 COVID Prosser 508

Economic Analysis of Vaccination
with mRNA Booster Dose
against COVID -19 Among Adults
University of Michigan
COVID -19 Vaccination Modeling Team
Presentation to ACIP
September 12, 2023
1
Study Team
University of Michigan
•Lisa A. Prosser, PhD, Principal Investigator
•David W. Hutton, PhD, Co -Investigator
•Acham Gebremariam, MS, Programmer/Analyst
•Angela Rose, MS, MPH, Project Manager
•Kerra Mercon, MS, Research Assistant
Wake Forest University
•Cara Janusz, PhD
Additional contributors to 2021 Covid Vaccination Model:
Marisa Eisenberg, Emily Martin, Grace Chung, Janamarie
Perroud, Ellen Kim Deluca, Chris Cadham, Huey -Fen Chen,
Anton L.V. Avancena, Tran Doan, David SuhCenters for Disease Control and Prevention
•Jamie Pike, PhD, Health Economist, Project officer
•Megan Wallace, DrPH, Epidemiologist
•Ismael Ortega -Sanchez, PhD, Senior Economist
•Andrew Leidner, PhD, Economist
•Fangjun Zhou, PhD, Health Scientist
•Melisa Shah, MD, MPH, Medical Epidemiologist
•Danielle Moulia, MPH, Health Scientist
•Ruth Link -Gelles, PhD, Epidemiologist
•Sharon Saydah, PhD, Epidemiologist
2
Conflict of interest statement
3Authors have no known conflicts of interest.
Objectives
•Estimate annual disease burden and healthcare utilization associated with
COVID -19 illness and COVID -19 booster vaccination, including cases of
symptomatic illness, hospitalizations, deaths, adverse events, costs, and quality -
adjusted life years
•Project cost -effectiveness of an updated mRNA booster against COVID -19-
associated illness in persons ages ≥18 years
4
Methods
•Intervention strategies:
oVaccination against COVID -19 illness with an updated “generic” mRNA booster
oNo updated mRNA booster (vaccination against COVID -19 illness with primary series only or
primary series plus current booster)
•Target population: all US adults, stratified by age
o18-49 y, 50 -64 y, 65+ y
oPediatric and adolescent age groups excluded from current analysis, insufficient data to
incorporate into this first phase analysis
•Time horizon: 1 year*
•Perspective: Societal
•Costing year: 2023$
•Discount rate: 3%
* Costs and QALYs lost due to long -term sequelae and deaths beyond one year are included
5
VaccinationSymptomatic
COVID -19
(non -hospitalized)
Hospitalized
COVID -19Non -medically
attended*
Outpatient visit
No ICU
admission
ICU admissionNo side
effects
Systemic
reaction
Anaphylaxis
Severe
adverse eventA
A
A
ANo booster
AB
No
complications
Long Covid
No ventilator
VentilatorB
CDeathModel schematic
No
COVID -19
COVID -19No long Covid
Long Covid
Long -term
sequelae C
No
complications
Long Covid
Death
6ED visit B
*Includes probability and costs of testing
ED= emergency department; ICU= intensive care unit
Analysis Plan
•Project health and economic outcomes stratified by intervention strategy and by
age subgroups (18 -49y, 50 -64y, 65+y)
oCases
oHospitalizations
oDeaths
oCosts
oQALYs
oAdverse events
•Calculate incremental cost -effectiveness ratios comparing updated mRNA booster
to no booster
•Conduct base case and uncertainty analyses (one -way sensitivity and scenario
analyses)
***This presentation reports preliminary results from the first phase of an ongoing
analysis***
7
Natural history:
probability of symptomatic infection, outpatient/ED
visits, hospitalization, and critical illness
8
Annual probability of symptomatic infection
9Overall
02000040000
12345678910111212345678910111212345
2021 2022 2023Rate/100,000/month
18-49y 50-64y 65+yLast 6 months
Source: HEROES -RECOVER, unpublished dataAnnualized probability
based on last 6 months
12/22 -5/23
18-49 y 0.3145
50-64 y 0.2841
65+ y 0.3339
Annual probability of symptomatic infection
10Annualized probability based on last 6 months
12/22 -5/23
Age group Base caseRange for sensitivity analysis
Low High
18-49 y 0.3145 0.2858 0.3444
50-64 y 0.2841 0.2438 0.3274
65+ y 0.3339 0.2312 0.4510
Source: HEROES -RECOVER, unpublished data
05001,0001,5002,0002,5003,000
10
202011 12 1
20212 3 4 5 6 7 8 9 10 11 12 1 2
20223 4 5 6 7 8 9 10Visits/100,000 Enrollees/month
18 - 49 Years 50 - 64 Years 65+ YearsProbability of an outpatient visit
11Annualized Probability based on last 6 months
5/22 -10/22
Age
groupBaseRange for sensitivity
analysis
Low High
18-49 y 0.075 0.022 0.110
50-64 y 0.106 0.041 0.159
65+ y 0.111 0.040 0.150Last 6 months
Source: Merative™MarketScan® Research Database, unpublished data
Probability of outpatient visits and ED visits given
symptomatic illness
12Age group BaseRange for sensitivity analysis
Low High
Outpatient visits given symptomatic illness
18 -49 y 0.157 0.1483 0.1664
50 -64 y 0.215 0.1991 0.2335
65+ y 0.244 0.1996 0.3088
Emergency department visits given symptomatic illness
18 -49 y 0.0184 0.0172 0.0196
50 -64 y 0.0191 0.0175 0.0210
65+ y 0.0394 0.0318 0.0505
Source: Derived using probability of an outpatient visit or ED visit from MarketScan data ( Merative™MarketScan® Research
Database, unpublished data) and probability of symptomatic illness in the HEROES -RECOVER data, May 2022 -October 2022
(unpublished)
050100150200250300350400
91011121234567891011121234567891011121234
2020 2021 2022 2023Rate/100,000/month
18-49 years 50-64 years 65+ yearsAnnual probability of hospitalization
13Annualized Probability based on last 6 months
10/22 -3/23
Age group Base caseRange
Low High
18-49 y 0.00144 0.00080 0.00204
50-64 y 0.00335 0.00216 0.00479
65+ y 0.01453 0.00967 0.02090Last 6 months
Source: COVID -NET, unpublished dataRate/100,000 based on last 6 months
10/22 -3/23
Age groupBase case
per 100,000Range
Low High
18-49 y 144 80 204
50-64 y 335 216 479
65+ y 1453 967 2090
Probability of critical illness given hospitalization
14Probability Base caseRange for sensitivity analysis (95% CI)
Low High
Probability ICU given hospitalization
18-49 y 0.123 0.119 0.145
50-64 y 0.200 0.178 0.208
65+ y 0.144 0.138 0.163
Probability ventilator use given ICU
18-49 y 0.525 0.472 0.577
50-64 y 0.488 0.445 0.532
65+ y 0.386 0.342 0.432
Source: COVID -NET, unpublished data
ICU= intensive care unit
Probability of death given hospitalization
15Source: COVID -NET, unpublished data
ICU= intensive care unitProbability Base caseRange (95% CI)
Low High
Probability of death given no ICU
18-49 y 0.006 0.002 0.008
50-64 y 0.009 0.007 0.016
65+ y 0.030 0.022 0.035
Probability of death given ICU without ventilator
18-49 y 0.024 0.003 0.040
50-64 y 0.047 0.026 0.077
65+ y 0.166 0.144 0.233
Probability of death given ICU with ventilator
18-49 y 0.284 0.213 0.368
50-64 y 0.379 0.301 0.435
65+ y 0.628 0.476 0.637
Probability of long COVID
16Age group Base caseRange
Low High
18-49 y 0.072 0.058 0.091
50-64 y 0.072 0.058 0.091
65+ y 0.072 0.058 0.091
Source: Montoy JCC et al. Prevalence of Symptoms ≤12 Months After Acute Illness, by COVID -19 Testing Status Among Adults —Unite d States, December 2020 –
March 2023. MMWR 2023; 72 (32): 859 -865.Assumptions :
•Derived to reflect 5 -month median duration of episode of long covid for individuals who experience
symptoms for 3+ months
•Average prevalence of HEENT, constitutional, pulmonary, musculoskeletal, cognitive, and fatigue symptoms
at 5 months
•Current estimates do not reflect higher risk associated with age or with severity of illness
Vaccine effectiveness & adverse events
17
Vaccine effectiveness: hospitalization, 18+ y
1862%
47%
24%57%
41%
12%67%
53%
33%
0%20%40%60%80%100%
0 73 146 219 292 365Vaccine Efficacy Against Hospitalization (%) Interval Days since Last Dose (days)VISION(Sep 2022 -May 2023)
62%
47%
24%
0%20%40%60%80%100%
0 73 146 219 292 365Vaccine Efficacy Against Hospitalization (%)
Interval Days since Last Dose (days)VISION (Sep 2022 -May 2023)
Source: VISION, bivalent booster, Sept 2022 -May 2023 . Link -Gelles R. Monovalent and bivalent VE against hospitalization among adults aged
≥18 years. Paper presented at: Advisory Committee on Immunization Practices. June 2023Conservative scenarioOptimistic scenario
Vaccine effectiveness: hospitalization, 18+ y
1954%
34%
6%39%
15%65%
50%
30%
0%20%40%60%80%100%
0 73 146 219 292 365Vaccine Efficacy against Hospitalization (%)
Interval Time since Last Dose (days)IVY (Sep 2022 -May 2023)
54%
34%
6%
0%20%40%60%80%100%
0 73 146 219 292 365Vaccine Efficacy against Hospitalization (%)
Interval Time since Last Dose (days)IVY (Sep 2022 -May 2023)
Source: IVY , bivalent booster, Sept 2022 -May 2023. Link-Gelles R. Monovalent and bivalent VE against hospitalization among adults aged
≥18 years. Paper presented at: Advisory Committee on Immunization Practices. June 2023Conservative scenarioOptimistic scenario
Vaccine effectiveness: hospitalization, 18+ y
20Source: VISION and IVY, bivalent vaccination,
Sept 2022 -May 2023 . Link -Gelles R. Monovalent
and bivalent VE against hospitalization among
adults aged ≥18 years. Paper presented at:
Advisory Committee on Immunization Practices.
June 2023Area under the curve: 0.2690%20%40%60%80%100%
0 73 146 219 292 365Vaccine Efficacy Against Hospitalization (%)
Interval Days since Last Dose (days)Lower boundUpper boundVISION (Sep 2022 -May 2023)
0%20%40%60%80%100%
0 73 146 219 292 365Vaccine Efficacy Against Hospitalization (%)
Interval Days since Last Dose (days)Lower boundUpper boundIVY (Sep 2022 -May 2023)
61%
46%
22%
0%20%40%60%80%100%
0 73 146 219 292 365Vaccine Efficacy Against Hospitalization (%)
Interval Days since Last Dose (days)Combined -VISION and IVY (Sep 2022 -May 2023)
Vaccine effectiveness, hospitalization, 18+ y
21Linear waning Conservative Optimistic
VISION
Base case 0.278 0.217 0.339
Lower bound 0.210 0.180 0.240
Upper bound 0.334 0.250 0.418
IVY
Base case 0.168 0.153 0.183
Lower bound 0.088 0.088 0.088
Upper bound 0.313 0.237 0.389
Base Case* 0.269 0.088 0.418
* Base case includes a weighted average of the area under the vaccine effectiveness (VE) curve with the assumption that VE wane s linearly after 180 days. Range s were
selected by taking the minimum and maximum of the individual dataset VEs, applying a conservative approach (assuming VE drops to0 at 180 days) for the lower bound
and an optimistic approach for the upper bound (assuming VE at 365 days=VE at 180 days)
Summary, vaccine effectiveness
22Base case Low High
Symptomatic illness (non -hospitalized)*
Hospitalization, uncomplicated 0.269 0.088 0.418
Hospitalization, critical illness** 0.403 0.191 0.671
Death 0.403 0.191 0.671
Source: VISION and IVY , Link-Gelles R. Monovalent and bivalent VE against hospitalization among adults aged ≥18 years. Paper
presented at: Advisory Committee on Immunization Practices. June 2023* Non -medically attended illness, illness that includes an outpatient or ED visit
** Intensive care unit with or without mechanical ventilation
Summary, vaccine effectiveness
23Base case Low High
Symptomatic illness (non -hospitalized)* 0.269 0.088 0.418
Hospitalization, uncomplicated 0.269 0.088 0.418
Hospitalization, critical illness** 0.403 0.191 0.671
Death 0.403 0.191 0.671
Source: VISION and IVY , Link-Gelles R. Monovalent and bivalent VE against hospitalization among adults aged ≥18 years. Paper
presented at: Advisory Committee on Immunization Practices. June 2023* Non -medically attended illness, illness that includes an outpatient or ED visit
** Intensive care unit with or without mechanical ventilation
Probability of adverse events
24Base caseRange for sensitivity analysis
Source
Low High
Systemic reaction
18-49 y 0.106 0.073 0.148
1,2 50-64 y 0.106 0.073 0.148
≥65 y 0.137 0.107 0.171
Anaphylaxis (all ages) 0.00000495 0.0000032 0.0000074 3
Death given anaphylaxis 0 0 0.00966 Assumption, 4
Myocarditis
18 -29 y 0.0000238 0.0000085 0.0000838 5
30-39 y 0.0000087 0.0000008 0.0000375 5
40+  y 0 0 0 Assumption
Death given myocarditis 0.0005 0 0.001 Expert opinion
1. U.S. Food and Drug Administration. Fact Sheet for Healthcare Providers Administering Vaccine: Emergency Use Authorization of Moderna COVID -19 Vaccine, Bivalent (Original
and Omicron BA.4/BA.5). In: U.S. Department of Health and Human Services, ed2023.
2. U.S. Food and Drug Administration. Fact Sheet for Healthcare Providers Administering Vaccine: Emergency Use Authorization o f Pfizer -Biontech COVID -19 Vaccine, Bivalent
(Original and Omicron BA.4/BA.5). In: U.S. Department of Health and Human Services, ed2023.
3. Klein NP, Lewis N, Goddard K, et al. Surveillance for Adverse Events After COVID -19 mRNA Vaccination. JAMA. 2021;326(14):1390 -1399.
4.Su JR, Moro PL, Ng CS, Lewis PW, Said MA, Cano MV. Anaphylaxis after vaccination reported to the Vaccine Adverse Event Repor ting System, 1990 -2016. J Allergy Clin Immunol.
2019;143(4):1465 -1473.
5. Kristin Goddard KEH, Ned Lewis,. Incidence of Myocarditis/Pericarditis Following mRNA COVID -19 Vaccination Among Children and Yo unger Adults in the United States. Annals of
Internal Medicine. 2022;175(12):1169 -1771.
Costs: Direct medical costs and productivity losses
25
Direct medical costs
Variable Base caseRange for sensitivity analysis
Source
Low High
Testing
Test cost $8 $8 $62 1,2
Probability of testing 0.05 0.02 0.20 3
Recipient time (hours) 0.50 0.25 1.50 Assumption
Outpatient visit
18-49 y $372 $370 $375
4 50-64 y $380 $377 $384
65+ y $391 $386 $396
Long Covid $1091 $1018 $1165 5
261. Justin Lo CC, Krutika Amin, Imani Telesford, Lindsey Dawson, and Jennifer Kates. Prices for COVID -19 testing. 2023; https://www.healthsystemtracker.org/brief/prices -for-covid -19-
testing/#Prices%20for%20COVID -19%20tests%20in%20the%20outpatient%20setting,%20among%20people%20with%20large%20employer%20health% 20coverage,%202021 .
2. Walmart. COVID -19 Test Kits.  https://www.walmart.com/browse/home -diagnostic -tests/covid -19-test-kits/976760_1005860_542089_3092061 . Accessed September 1, 2023.
3. Rader B GA, Iuliano AD,. Use of At -Home COVID -19 Tests —United States, August 23, 2021 –March 12, 2022
4. Merative™MarketScan® Research Database, unpublished data
5. Pike J et al. Direct Medical Costs Associated With Post –COVID -19 Conditions Among Privately Insured Children and Adults. Prev Ch ronic Dis. 2023;20 (6)
Direct medical costs, cont.
Variable Base caseRange for Sensitivity Analysis
Low High
Hospitalization episode
18-49 y$32,514 $28,505 $36,523
50-64 y$32,854 $31,450 $34,258
65+ y$20,648 $20,295 $21,000
ICU episode (no ventilator)
18-49 y $37,159 $30,116 $44,203
50-64 y $46,727 $40,269 $53,186
65+ y $23,220 $22,408 $24,032
ICU (with ventilator) episode
18-49 y $245,432 $168,362 $322,503
50-64 y $169,189 $140,250 $198,129
65+ y $55,257 $50,705 $59,809
27ICU= Intensive care unitSource: Merative ™MarketScan® Research Database, unpublished data
Medication costs
Variable Base caseRange for Sensitivity Analysis
Source
Low High
Over the counter medication* $4.12 - - 1
Probability of nirmatrelvir -r prescription
given an outpatient visit
18-49 years 0.1751 0.10 0.30
2,3, Assumption 50-64 years 0.2696 0.10 0.50
65+ years 0.2739 0.10 0.50
Cost, nirmatrelvir -r $530 $530 $1200 4, 5
28*5 days of generic cold/flu medicine
1. Target.com Accessed August 29, 2023.
2. HealthVerity, Inc. COVID -19 database licensed by CDC, unpublished data
3. Merative™MarketScan® Research Database, unpublished data
4. Recht H. Paxlovid Has Been Free So Far. Next Year, Sticker Shock Awaits. 2022; https://kffhealthnews.org/news/article/paxlovid -covid -sticker -shock -
insurance/#:~:text=The%20U.S.%20government%20has%20so,in%20a%20July%20earnings%20call .
5. Murez C. Paxloid soon won’t be free for Americans. 2022  https://www.usnews.com/news/health -news/articles/2022 -12-07/paxlovid -soon -wont -be-free-for-americans . Accessed September 7, 2023
Vaccine receipt, costs
Variable Base caseRange for Sensitivity Analysis
Source
Low High
mRNA monovalent booster, per dose* $120 $30 $200 1, expert opinion
Administration, per dose** $20.33 $18.07 $26.58 2
Vaccination setting
Proportion, pharmacy 0.644 0.625 0.663 3
Proportion, physician office visit 0.256 0.221 0.294 3
Proportion, mass vaccination 0.100 0.075 0.155 3
Recipient time by vaccination setting (hours)
Pharmacy 0.25 0.083 0.50 4, expert opinion
Physician office 1.19 0.17 2 4
Mass vaccination 0.195 0 0.390 4
Mean hourly earnings $33.74 $23.98 $50.16 5
29*Lower bound reflects current price of COVID -19 boosters
**CPT 90471
1. Kates J et al. How much could COVID -19 vaccines cost the US after commercialization? 2023. https://www.kff.org/coronavirus -covid-19/issue -brief/how -much -could -covid -19-vaccines -cost-the-u-s-after -
commercialization/
2. Centers for Medicare & Medicaid Service. Search the Physician Fee Schedule. 2023; https://www.cms.gov/medicare/physician -fee-schedule/search?Y=0&T=0&HT=0&CT=3&H1=90471&M=5
3. CDC national survey data, 2/10/23 -5/1/23, unpublished
4. Prosser L, O'Brien M, Molinari N, et al. Non -traditional settings for influenza vaccination of adults: Costs and cost -effectiv eness. Pharmacoeconomics. 2008;26(2):163 -178.
5.US Bureau of Labor Statistics. Average hourly and weekly earnings of all employees on private nonfarm payrolls by industry se ctor, seasonally adjusted. 2023; https://www.bls.gov/news.release/empsit.t19.htm
Vaccination -associated adverse events, costs
Variable Base caseRange for Sensitivity AnalysisSource
Low High
Systemic reaction
Physician visit $90.82 $82.72 $115.84 1
Productivity loss (days) 1 - - Assumption
Anaphylaxis
Hospitalization $5035 2*
Productivity loss (days) 1 1 3 3
Myocarditis/pericarditis
Hospitalization $75,927 4**
Productivity loss (days) 4 0 14 5, 6, Expert opinion
30* HCUP -NIS 2012 estimates (mean LOS = 4.9 days) adjusted to 1 days LOS
** HCUP -NIS 2014 estimates (mean LOS = 7.4 days) adjusted to 4 days LOS
1. Centers for Medicare & Medicaid Service. Search the Physician Fee Schedule. 2023; https://www.cms.gov/medicare/physician -fee-schedule/search?Y=0&T=0&HT=0&CT=3&H1=90471&M=5
2. Candrilli S, Kurosky SK. Recent Trends In Anaphylaxis -Related Hospitalization In The United States. Value in Health. 2015;18(7):A503.
3. Shimabukuro T, Cole M, Su JR. Reports of Anaphylaxis After Receipt of mRNA COVID -19 Vaccines in the US -December 14, 2020 -Januar y 18, 2021. Jama. 2021;325(11):1101 -1102.
4. Khorolsky C, Shi J, Chkhikvadze T. Trends In Hospitalization Costs, Length Of Stay And Complications Among Patients With Acut e Myocarditis: A 10 -Year United States Perspective. Journal of the American College
of Cardiology. 2019;73(9_Supplement_1):935 -935.
5. Marshall M, Ferguson I, Lewis P, et al. Symptomatic Acute Myocarditis in Seven Adolescents Following Pfizer -BioNTech COVID -19 Va ccination. Pediatrics. 2021.
6. Shimabukuro T. COVID -19 Vaccine Safety Updates. In. Advisory Committee on Immunization Practices (ACIP)2021.
Quality adjustments
31
QALY losses, COVID -19 illness
32Variable Base CaseRange for Sensitivity Analysis
QALDs lostLow High
Symptomatic illness* 0.006 0.004 0.008 2.2 (1.5 -2.9)
Hospitalization 0.027 - - 9.9
Critical illness** 0.054 - - 19.7
Long COVID 0.067 0.038 0.088 24.3 (13.7 -31.9)
* Non -medically attended and outpatient illness
** Intensive care unit with mechanical ventilation. Derived by applying the ratio of ICU to hospitalization QALY loss (2x) to the
hospitalization QALY loss from SARS CoV -2 EQ5D Study. The model also includes a health state for ICU care without ventilator use for
which QALY loss is interpolated using QALY loss for hospitalization and critical illnessDRAFT
Source: Coronavirus Household Evaluation and Respiratory Testing (C -HEaRT) and Prospective Assessment of COIVD -19 in a Community (PACC), unpublished data
QALY loss, vaccination -associated AEs
33Variable Base CaseRange for Sensitivity Analysis
QALDs lost Source
Low High
Systemic reaction (QALY loss)*
All ages 0.0004 0.0003 0.0005 0.15 (0.11 -0.18) Assumption
Anaphylaxis (QALY loss)
All ages 0.0137 0.0135 0.0139 5.0 (0.93 -5.08) 1
Myocarditis/pericarditis (QALY loss)
Acute illness** 0.010 0.0086 0.0112 3.65 (3.14 -4.09) 2
* QALY loss equal to one day of COVID -19 illness
** Derived from health utility for COVID -19 related myocarditis. Assumed 2 -week illness
QALY= Quality -adjusted life year; QALD= Quality -adjusted life day
1. Prosser LA, Payne K, Rusinak D, Shi P, Uyeki TM, Messonnier ML. Valuing health across the lifespan: health state preferences forseasonal influenza illnesses in patients of different ages. Value in
Health. 2011;14(1):135 -143.
2. Morrow AJ, Sykes R, McIntosh A, et al. A multisystem, cardio -renal investigation of post -COVID -19 illness. Nature Medicine. 2022;28(6):1303 -1313
Results
preliminary estimates
34
Disaggregated results, per 100,000
preliminary estimates
Age
groupStrategyCases Cases Averted
Cases Hosp ICU Deaths Cases Hosp ICU Deaths
18-49 y No booster 31,450 144 17.7 3.6 - - - -
Booster dose 22,990 105 10.6 2.2 8,460 39 7.1 1.4
50-64y No booster 28,410 335 67.1 16.4 - - - -
Booster dose 20,768 245 40.0 9.9 7,642 90 27.0 6.6
65+ yNo booster 33,390 1,453 209.3 109.4 - - - -
Booster dose 24,408 1,062 124.9 66.0 8,982 391 84.3 43.4
35
Incremental cost -effectiveness ratios,
societal perspective, per 1000
preliminary estimates
Age group StrategyProjected
CostsIncremental
CostsProjected
QALYsIncremental
QALYs$/QALY
18-49 y No booster $192,335 - 20207.0670 - -
Booster vaccination $293,503 $101,168 20207.9423 0.8752 $115,588
50-64y No booster $385,752 - 12275.8345 - -
Booster vaccination $421,249 $35,498 12277.2111 1.3766 $25,787
65+ y No booster $642,488 - 6519.9466 - -
Booster vaccination $598,857 -$43,630 6523.5511 3.6046 Cost -saving
36QALY= quality -adjusted life year
Incremental cost -effectiveness ratios,
societal perspective, per 1000
preliminary estimates, w/pooled 18+
Age groupBooster Dose,
$/QALY
18-49 y$115,588
50-64 y$25,787
65+ yCost -saving
18+ y$33,437
37QALY= quality -adjusted life year
One way sensitivity analyses, 18 -49 y
preliminary estimates
38Base case: $115,588 *Non -hospitalized cases
Note: Numbers next to bars indicate input values for sensitivity analysis
VE=vaccine effectiveness; QALY=Quality -adjusted life year$0 $50,000 $100,000 $150,000 $200,000 $250,000 $300,000Probability, symptomatic COVID-19Time (h), vaccination, doctor's officeLifetime productivity costVE, hospitalizationProbability, death given ICU with ventilatorQALYs lost symptomatic COVIDProbability, hospitalizationVE, critical illnessVE, symptomatic COVID-19Cost, vaccine
$/QALY$30 $200
0.418 0.088
0.671 0.191
0.002 0.0008
0.008 0.004
0.368 0.213
0.418 0.088
$2,382,347
0.17 2
0.344 0.286*
VE scenario analyses
preliminary estimates
Base case Scenario 1 Scenario 2 Scenario 4 Scenario 5
VE inputs
Symptomatic illness 0.269 0.088 0.418 0.269 0.403
Hospitalization, uncomplicated 0.269 0.088 0.418 0.269 0.403
Hospitalization, critical illness 0.403 0.191 0.671 0.269 0.403
Death 0.403 0.191 0.671 0.269 0.403
$/QALY
18-49 y $115,588 $435,886 $45,376 $141,155 $70,928
50-64 y $25,787 $199,830 Cost -saving $51,792 $3,001
65+ y Cost -saving $51,782 Cost -saving Cost -saving Cost -saving
39VE= vaccine effectiveness; QALY= quality -adjusted life year
Scenario analyses:
probability of symptomatic illness, non -hospitalized*
preliminary estimates
40Age group Base case 0.1 0.2 0.3 0.4 0.5
18-49 y $115,588 $229,724 $160,000 $120,013 $94,082 $75,905
50-64 y $25,787 $48,937 $34,724 $24,324 $16,384 $10,123
65+ y Cost -saving Cost -saving Cost -saving Cost -saving Cost -saving Cost -saving
QALY=Quality -adjusted life year
*One -way sensitivity analysis of non -hospitalized symptomatic illness varied separately from hospitalization and critical illnes s;
base case probability of symptomatic illness: 18 -49 y, 0.3145; 50-64 y, 0.2841; 65+ y, 0.3339
Scenario analysis:
probability of hospitalization
preliminary estimates
41Age group Base case* 2x base case 3x base case 4x base case
18-49 y $115,588 $51,978 $14,541 Cost -saving
50-64 y $25,787 Cost -saving Cost -saving Cost -saving
65+ y Cost -saving Cost -saving Cost -saving Cost -saving
QALY=Quality -adjusted life year
*Base case probability of h ospitalization 18-49 y-0.00144; 50 -64 y-0.00335; 65+ -0.01453
Scenario analysis: probability of critical care
preliminary estimates
42Age groupProbability of ICU given hospitalization
Base case* 2x 3x 4x
18-49 y $115,588 $71,487 $42,307 $21,570
50-64 y $25,787 Cost -saving Cost -saving Cost -saving
65+ y Cost -saving Cost -saving Cost -saving Cost -saving
QALY=Quality -adjusted life year; ICU= Intensive care unit
*Base case probability of ICU given hospitalization: 18 -49 y-0.123; 50 -64 y-0.200, 65+ y -0.144
Scenario analysis: vaccine setting
preliminary estimates
43Age group Base case*100%
pharmacy100%
physician office100%
mass vaccination
18-49 y $115,588 $106,523 $142,759 $104,403
50-64 y $25,787 $20,024 $43,063 $18,676
65+ y Cost -saving Cost -saving Cost -saving Cost -saving
QALY=Quality -adjusted life year
*Base case : Physician office visit -0.256, Pharmacy -0.644, Mass vaccination -0.100
Limitations
▪Unpublished data used to derive key parameters in the model: vaccine effectiveness,
symptomatic illness, probabilities of hospitalization and critical illness
▪Data sources vary in representativeness, generalizability
▪VE estimates derived from data on bivalent booster
▪Hospitalization rates may overestimate cases due to COVID -19 for younger age groups
▪MarketScan data for ages 65+ only includes those with supplemental insurance
▪Evidence base for long covid is especially scarce –future analyses will incorporate adjustments
to reflect differences in probability and duration of long covid by age and severity of illness
▪Cost estimates for long covid may not reflect current practice patterns or rates of HC utilization
44
Summary -preliminary estimates
•Vaccination averts substantial morbidity and mortality as
demonstrated through estimated disaggregated outcomes
•ICERs for 50 -64y and 65+ age groups are robust to changes in
parameter inputs across plausible ranges in all but one scenario
(<$51,800 or cost -saving)
•ICERs for 18 -49y are sensitive to changes in parameter inputs; more
favorable for higher VE, higher risk of hospitalization and critical
illness
45

Summary: Economic Analysis of Vaccination with mRNA Booster Dose  against COVID -19 Among Adults University of Michigan  COVID -19 Vaccination Modeling Team Presentation to ACIP September 12, 2023 1 Study Team University of Michigan •Lisa A. Prosser, PhD, Principal Investigator •David W. Hutton, PhD, Co -Investigator •Acham Gebremariam, MS, Programmer/Analyst •Angela Rose, MS, MPH, Project Manager •Kerra Mercon, MS, Research Assistant Wake Forest University •Cara Janusz, PhD Additional contributors to…


07 COVID Klein 508

COVID -19 Vaccine Safety Surveillance:
Summary from VSD RCA
Nicola Klein, MD, PhD
Director, Kaiser Permanente Vaccine Study Center
Kaiser Permanente Northern California
Advisory Committee in Immunization Practices
September 12, 2023

2Vaccine Safety Datalink
•Active surveillance: newly licensed vaccines
̶Rapid Cycle Analysis (RCA)
•Evaluate vaccine safety:
̶of new recommendations for existing vaccines
̶for vaccines in high -risk populations, particularly pregnant women
(+ other groups)
•Develop new methods for vaccine safety assessment
•Test hypotheses that emerge from elsewhere (e.g.,
VAERS, clinical trials, other platforms).

Strengths of VSD Rapid Cycle Analysis (RCA)
▪Population
•~12.5 million people (equal to ~4% of the U.S. population) across VSD data sites are geographically and
racially/ethnically diverse
▪Data
•Near real -time data, with analyses updated weekly
•Access to comprehensive medical records, including exposures (vaccination) and outcomes, allowing
rapid chart reviews to obtain additional clinical information as needed
▪Innovative Methods
•Vaccinated concurrent comparators : Recent vaccinees who are beyond their risk interval are expected to
be  similar to current vaccinees who are within their risk interval. They serve as better comparators than
unvaccinated individuals, historical controls or non -concurrent self controls because they permit:
‒Careful adjustment for potential biases associated with calendar time, site, and demographic
factors
‒Analyses that can begin sooner than alternative methods
•Supplemental analyses conducted weekly: Unvaccinated/un -boosted comparators would also be available
to provide context in real time
3
Aims:
1. To monitor the safety of COVID -19 vaccines weekly using pre -
specified outcomes of interest among VSD members.
2. To describe the uptake of COVID -19 vaccines over time
among eligible VSD members overall and in strata by age, site,
and race/ethnicity.
Surveillance began in December 2020 and was ready when
the first doses of COVID -19 vaccines were given.VSD COVID -19 Vaccine RCA
4
Inclusion in prior vaccine safety studies
•Acute disseminated encephalomyelitis
•Anaphylaxis*
•Encephalitis / myelitis
•Guillain -Barré syndrome
•Immune thrombocytopenia
•Kawasaki disease
•Narcolepsy and cataplexy*
•Seizures
•Transverse myelitis Hypothetical concerns regarding an
association with COVID -19 disease
•Acute myocardial infarction
•Acute respiratory distress syndrome*
•Disseminated intravascular coagulation
•Multisystem Inflammatory Syndrome*
•Pulmonary embolism
•Stroke, hemorrhagic
•Stroke, ischemic
•Thrombotic thrombocytopenic purpura
•Venous thromboembolism
5•Cerebral venous sinus thrombosis
•Myocarditis / pericarditis
•Thrombosis with thrombocytopenia syndromeOutcomes added/enhanced due to emerging
concerns
Imbalances in phase 3 COVID -19 vaccine clinical
trials
•Appendicitis
•Bell’s palsy
*monitored without comparators Only chart confirmed cases
COVID Vaccine Safety RCA Surveillance: Monitoring
23 Serious Outcomes

Vaccinee with Myocarditis in Risk Interval and a Concurrent Comparator
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
May 31
Risk Interval 1 -21 days post -vaccination21
June 3
Vaccinated
May 30
6
7September: Interim mRNA vaccines safety
surveillance, including myocarditis/pericarditis risk
(JAMA )September:
Bivalent boosters
Pfizer (≥12y) and
Moderna (≥18y)September: Bivalent
boosters. Monovalent
boosters discontinuedMay: Pfizer
monovalent
booster 5 -
11yMarch: 2nd
monovalent
booster
(≥50y)January:
Pfizer
monovalent
booster
12-15ySeptember/October:
Adult monovalent
booster; Pfizer
(≥16y), Moderna and
Janssen (≥18y)
October: Myocarditis/pericarditis
rates after primary and monovalent
boosters <40y ( Ann Int Med )August: Risk of myocarditis/
pericarditis Pfizer vs Moderna
(Vaccine )April: GBS following
Janssen vaccine ( JAMA
Network Open )December:
EUA Moderna
(≥18y) and
Pfizer (≥16y)
November/December: first
VSD signal, ischemic stroke
after bivalent Pfizer ≥65y
October:
Bivalent
boosters Pfizer
(5-11y) and
Moderna (6 -17y)December:
Bivalent boosters
Pfizer (6m -4y) and
Moderna (6m -5y)May: EUA
Pfizer 12 -
15y
May:
myocarditis/
pericarditis
after mRNA
vaccines
reportedAugust: FDA
approves
Pfizer (≥16y)
October:
EUA Pfizer
5-11y January: FDA
approves
Moderna
(≥18y) May 2022: Janssen
vaccine no longer
recommendedJune: EUA Pfizer (6m –4y),
Moderna (6m –17y)
July: EUA
Novavax
vaccine (≥18y)2020
Primary
Series
Monovalent
Boosters
Bivalent mRNA
Boosters
VSD COVID -19 RCA
Safety Publications2021 2022 2023
March: >200
million doses
given in US
by the end
AprilApril:
Janssen
and CVST
concernsFebruary:
Janssen
EUA
(≥18y)
June : mRNA
vaccine safety
6m-5y (Pediatrics )July: FDA
safety
warning re:
GBS and
Janssen.
8

Results using vaccinated concurrent
comparators
9
Klein NP, Lewis N, et. al. JAMA . Published online  September 03, 2021. doi:10.1001/jama.2021.1507210
Outcomes Monitored Without Comparators
11
12
JAMA . Published online  September 03, 2021. doi:10.1001/jama.2021.15072
VSD COVID -19 RCA Surveillance:
Outcomes Monitored Due to Emerging Concerns
13
14September: Interim mRNA vaccines safety
surveillance, including myocarditis/pericarditis risk
(JAMA )September:
Bivalent boosters
Pfizer (≥12y) and
Moderna (≥18y)September: Bivalent
boosters. Monovalent
boosters discontinuedMay: Pfizer
monovalent
booster 5 -
11yMarch: 2nd
monovalent
booster
(≥50y)January:
Pfizer
monovalent
booster
12-15ySeptember/October:
Adult monovalent
booster; Pfizer
(≥16y), Moderna and
Janssen (≥18y)
October: Myocarditis/pericarditis
rates after primary and monovalent
boosters <40y ( Ann Int Med )August: Risk of myocarditis/
pericarditis Pfizer vs Moderna
(Vaccine )April: GBS following
Janssen vaccine ( JAMA
Network Open )December:
EUA Moderna
(≥18y) and
Pfizer (≥16y)
November/December: first
VSD signal, ischemic stroke
after bivalent Pfizer ≥65y
October:
Bivalent
boosters Pfizer
(5-11y) and
Moderna (6 -17y)December:
Bivalent boosters
Pfizer (6m -4y) and
Moderna (6m -5y)May: EUA
Pfizer 12 -
15y
May:
myocarditis/
pericarditis
after mRNA
vaccines
reportedAugust: FDA
approves
Pfizer (≥16y)
October:
EUA Pfizer
5-11y January: FDA
approves
Moderna
(≥18y) May 2022: Janssen
vaccine no longer
recommendedJune: EUA Pfizer (6m –4y),
Moderna (6m –17y)
July: EUA
Novavax
vaccine (≥18y)2020
Primary
Series
Monovalent
Boosters
Bivalent mRNA
Boosters
VSD COVID -19 RCA
Safety Publications2021 2022 2023
March: >200
million doses
given in US
by the end
AprilApril:
Janssen
and CVST
concernsFebruary:
Janssen
EUA
(≥18y)
June : mRNA
vaccine safety
6m-5y (Pediatrics )July: FDA
safety
warning re:
GBS and
Janssen.
Myocarditis and Pericarditis
Following mRNA Vaccines
15
Myocarditis / Pericarditis Among Subgroup
<40 Years of Age
17•Chart reviews began May 2021
•All identified cases of myocarditis/pericarditis during the 98 days after
vaccination were chart reviewed, followed by infectious disease clinician
and/or a cardiologist adjudication to:
•Confirm case was incident following vaccination
•Met CDC case definition (myocarditis, pericarditis, or myopericarditis)
•Evaluated level of certainty for myocarditis
Clustering of Confirmed Myocarditis/pericarditis by Days Since Most
Recent Dose of any mRNA Vaccine Among 12 -39 Year -Olds
18
JAMA . Published online  September 03, 2021. doi:10.1001/jama.2021.15072
19
Klein NP, Lewis N, et. al. JAMA . Published online  September 03, 2021. doi:10.1001/jama.2021.15072
•No safety signals for any outcome in the 21 days after both mRNA doses in
the overall VSD population, including all ages ≥12 years.
•In the subgroup aged 12 –39 years, the rate ratio for myocarditis/pericarditis
was elevated after both Pfizer and Moderna during days 0 -21 after
vaccination, and especially during days 0 -7.
̶In subgroup analyses, both mRNA vaccines were associated with
myocarditis/pericarditis in persons aged 12 -39 years.
•In the VSD, rate of anaphylaxis after mRNA vaccines was ~ 5 cases / million
doses.
•VSD surveillance was ongoing.Summary
(data through June 2021)
20
21September: Interim mRNA vaccines safety
surveillance, including myocarditis/pericarditis risk
(JAMA )September:
Bivalent boosters
Pfizer (≥12y) and
Moderna (≥18y)September: Bivalent
boosters. Monovalent
boosters discontinuedMay: Pfizer
monovalent
booster 5 -
11yMarch: 2nd
monovalent
booster
(≥50y)January:
Pfizer
monovalent
booster
12-15ySeptember/October:
Adult monovalent
booster; Pfizer
(≥16y), Moderna and
Janssen (≥18y)
October: Myocarditis/pericarditis
rates after primary and monovalent
boosters <40y ( Ann Int Med )August: Risk of myocarditis/
pericarditis Pfizer vs Moderna
(Vaccine )April: GBS following
Janssen vaccine ( JAMA
Network Open )December:
EUA Moderna
(≥18y) and
Pfizer (≥16y)
November/December: first
VSD signal, ischemic stroke
after bivalent Pfizer ≥65y
October:
Bivalent
boosters Pfizer
(5-11y) and
Moderna (6 -17y)December:
Bivalent boosters
Pfizer (6m -4y) and
Moderna (6m -5y)May: EUA
Pfizer 12 -
15y
May:
myocarditis/
pericarditis
after mRNA
vaccines
reportedAugust: FDA
approves
Pfizer (≥16y)
October:
EUA Pfizer
5-11y January: FDA
approves
Moderna
(≥18y) May 2022: Janssen
vaccine no longer
recommendedJune: EUA Pfizer (6m –4y),
Moderna (6m –17y)
July: EUA
Novavax
vaccine (≥18y)2020
Primary
Series
Monovalent
Boosters
Bivalent mRNA
Boosters
VSD COVID -19 RCA
Safety Publications2021 2022 2023
March: >200
million doses
given in US
by the end
AprilApril:
Janssen
and CVST
concernsFebruary:
Janssen
EUA
(≥18y)
June : mRNA
vaccine safety
6m-5y (Pediatrics )July: FDA
safety
warning re:
GBS and
Janssen.
22Sequential Test1
Outcome Event in
Risk
IntervalAdjusted Rate
Ratio (95% CI)21-sided
P-value'Signal’ 1 -
sided p
<0.0048?
Myocarditis /
pericarditis 138 1.72 <0.001 YesRCA Signal* for Myocarditis/Pericarditis in the 1 -21 Day Risk
Interval, all VSD population ≥12 years
Compared with Outcome Events in Vaccinated Comparators on the Same Calendar Days
*signal as of August 20211Sequential test requires 1 -sided p < 0.0048 for a signal. This keeps the probability of a false positive signal (due to chance
alone) below 0.05 in 2 years of surveillance.
2Adjusted for VSD site, 5 -year age group, sex, race/ethnicity, and calendar date. Comparison interval is 22 –42 days after
either dose.
23
•This study assessed whether the risk of myocarditis/pericarditis
after Moderna differs from that after Pfizer
•We conducted both indirect and direct head -to-head
comparisons among 18 –39-year-olds
24
Verified Myocarditis and Pericarditis in the 0 -7 Day Risk Interval, among 18 –39-
Year -Olds by Product and Dose, December 14, 2020 -January 14, 2022
Compared with Outcome Events in Vaccinated Comparators on the Same Calendar Days
Goddard, et al. Vaccine .
Head -to-Head Comparison of Moderna versus Pfizer Regarding Myocarditis and
Pericarditis During Days 0 -7 Day Post -Vaccination in 18 –39-Year -Olds
25
➢Risk estimates of myocarditis/pericarditis in 18 –39-year-olds during days 0 -7
after 2 doses were modestly higher after Moderna than after Pfizer.
26
Goddard K, et al. .Ann Intern Med . 2022;175:1169 -1771.* Data through August 20, 2022
VSD incidence rates of verified myocarditis or pericarditis in the 0 –7 days after mRNA
vaccination in 5 –39-year-olds, by product, age groups, sex and dose number*
27September: Interim mRNA vaccines safety
surveillance, including myocarditis/pericarditis risk
(JAMA )September:
Bivalent boosters
Pfizer (≥12y) and
Moderna (≥18y)September: Bivalent
boosters. Monovalent
boosters discontinuedMay: Pfizer
monovalent
booster 5 -
11yMarch: 2nd
monovalent
booster
(≥50y)January:
Pfizer
monovalent
booster
12-15ySeptember/October:
Adult monovalent
booster; Pfizer
(≥16y), Moderna and
Janssen (≥18y)
October: Myocarditis/pericarditis
rates after primary and monovalent
boosters <40y ( Ann Int Med )August: Risk of myocarditis/
pericarditis Pfizer vs Moderna
(Vaccine )April: GBS following
Janssen vaccine ( JAMA
Network Open )December:
EUA Moderna
(≥18y) and
Pfizer (≥16y)
November/December: first
VSD signal, ischemic stroke
after bivalent Pfizer ≥65y
October:
Bivalent
boosters Pfizer
(5-11y) and
Moderna (6 -17y)December:
Bivalent boosters
Pfizer (6m -4y) and
Moderna (6m -5y)May: EUA
Pfizer 12 -
15y
May:
myocarditis/
pericarditis
after mRNA
vaccines
reportedAugust: FDA
approves
Pfizer (≥16y)
October:
EUA Pfizer
5-11y January: FDA
approves
Moderna
(≥18y) May 2022: Janssen
vaccine no longer
recommendedJune: EUA Pfizer (6m –4y),
Moderna (6m –17y)
July: EUA
Novavax
vaccine (≥18y)2020
Primary
Series
Monovalent
Boosters
Bivalent mRNA
Boosters
VSD COVID -19 RCA
Safety Publications2021 2022 2023
March: >200
million doses
given in US
by the end
AprilApril:
Janssen
and CVST
concernsFebruary:
Janssen
EUA
(≥18y)
June : mRNA
vaccine safety
6m-5y (PediatricsJuly: FDA
safety
warning re:
GBS and
Janssen.
•Findings were consistent withanassociation between increased riskofGBS and
Janssen COVID -19vaccine.
̶When directly compared withmRNA vaccines, t heriskofGBS after Janssen vaccine was21times
higher .
•Noevidence ofassociation between GBS andmRNA -based COVID -19vaccines.
̶Incidence ofGBS inthe21days after mRNA vaccines wassimilar totheexpected background rate
̶Nostatistical signals inweekly surveillance withvaccinated concurrent comparators
•Since publication and through February 2023, VSD identified 5 additional confirmed
cases of GBS: 4 after mRNA vaccines and 1 after Janssen.
̶2 were in 1 -21 risk interval (1 mRNA, 1 Janssen), 1 in 22 –42 day interval, and 2 in 43 –84 day interval.
̶All new cases were among males aged 55 -65 years, except one case in a 4 -year-old male.
•ACIP preferentially recommended mRNA -based COVID -19vaccines over Janssen
vaccine in December 2021. (https://www.cdc.gov/mmwr/volumes/71/wr/pdfs/mm7103a4 -H.pdf )
̶FDA revoked Janssen EUA as of June 2023. (https://www.fda.gov/vaccines -blood -biologics/coronavirus -covid -19-cber -regulated -biologics/janssen -
covid -19-vaccine )Summary: Guillain -Barre After COVID -19 Vaccination in the VSD
28(JAMA Netw Open. 2022;5(4):e228879. https://doi.org/10.1001/jamanetworkopen.2022.8879 )
29September: Interim mRNA vaccines safety
surveillance, including myocarditis/pericarditis risk
(JAMA )September:
Bivalent boosters
Pfizer (≥12y) and
Moderna (≥18y)September: Bivalent
boosters. Monovalent
boosters discontinuedMay: Pfizer
monovalent
booster 5 -
11yMarch: 2nd
monovalent
booster
(≥50y)January:
Pfizer
monovalent
booster
12-15ySeptember/October:
Adult monovalent
booster; Pfizer
(≥16y), Moderna and
Janssen (≥18y)
October: Myocarditis/pericarditis
rates after primary and monovalent
boosters <40y ( Ann Int Med )August: Risk of myocarditis/
pericarditis Pfizer vs Moderna
(Vaccine )April: GBS following
Janssen vaccine ( JAMA
Network Open )December:
EUA Moderna
(≥18y) and
Pfizer (≥16y)
November/December: first
VSD signal, ischemic stroke
after bivalent Pfizer ≥65y
October:
Bivalent
boosters Pfizer
(5-11y) and
Moderna (6 -17y)December:
Bivalent boosters
Pfizer (6m -4y) and
Moderna (6m -5y)May: EUA
Pfizer 12 -
15y
May:
myocarditis/
pericarditis
after mRNA
vaccines
reportedAugust: FDA
approves
Pfizer (≥16y)
October:
EUA Pfizer
5-11y January: FDA
approves
Moderna
(≥18y) May 2022: Janssen
vaccine no longer
recommendedJune: EUA Pfizer (6m –4y),
Moderna (6m –17y)
July: EUA
Novavax
vaccine (≥18y)2020
Primary
Series
Monovalent
Boosters
Bivalent mRNA
Boosters
VSD COVID -19 RCA
Safety Publications2021 2022 2023
March: >200
million doses
given in US
by the end
AprilApril:
Janssen
and CVST
concernsFebruary:
Janssen
EUA
(≥18y)
June : mRNA
vaccine safety
6m-5y (Pediatrics )July: FDA
safety
warning re:
GBS and
Janssen.
30
Monovalent Booster Uptake Among Persons Aged≥12 Years in the VSD, Over Time*
* Data through September 10, 2022 when monovalent booster were discontinued in favor of bivalent boosters.

Summary of RCA Findings in the 1 -21 Day Risk Interval After Monovalent Boosters ≥12 Years
Compared with Outcome Events 22 -42 Days After in Vaccinated Comparators*
➢Following mRNA primary series and monovalent booster , only myocarditis/pericarditis met the
signaling criteria in the 21 days among ages ≥12 years in the VSD population.Signal?** Signal?**
*Final analyses through September 2022
**Signaling threshold P<0.01 (one -sided)
Signal?** Signal?** Signal?** Signal?** Signal?** Signal?**
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.
4One 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.
5Two 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
Monovalent
Booster312 -17 Pfizer415 4 7.21 2.04 –29.66 0.002 59.9 (34.3 –97.3)
18–39 Either 22 10 4.46 2.02 –10.37 <0.001 15.8 (9.9 –23.9)
18–39 Pfizer 11 5 4.81 1.55 –16.81 0.006 14.3 (7.1 –25.5)
18–39 Moderna56 4 3.27 0.82 –14.23 0.093 16.8 (7.3 –33.1)
32Verified Myocarditis and Pericarditis in0–7 Days Following
Monovalent Booster in 12 –39-Year -Olds
Compared with Events on the Same Calendar Days among Boosted Comparators
33September: Interim mRNA vaccines safety
surveillance, including myocarditis/pericarditis risk
(JAMA )September:
Bivalent boosters
Pfizer (≥12y) and
Moderna (≥18y)September: Bivalent
boosters. Monovalent
boosters discontinuedMay: Pfizer
monovalent
booster 5 -
11yMarch: 2nd
monovalent
booster
(≥50y)January:
Pfizer
monovalent
booster
12-15ySeptember/October:
Adult monovalent
booster; Pfizer
(≥16y), Moderna and
Janssen (≥18y)
October: Myocarditis/pericarditis
rates after primary and monovalent
boosters <40y ( Ann Int Med )August: Risk of myocarditis/
pericarditis Pfizer vs Moderna
(Vaccine )April: GBS following
Janssen vaccine ( JAMA
Network Open )December:
EUA Moderna
(≥18y) and
Pfizer (≥16y)
November/December: first
VSD signal, ischemic stroke
after bivalent Pfizer ≥65y
October:
Bivalent
boosters Pfizer
(5-11y) and
Moderna (6 -17y)December:
Bivalent boosters
Pfizer (6m -4y) and
Moderna (6m -5y)May: EUA
Pfizer 12 -
15y
May:
myocarditis/
pericarditis
after mRNA
vaccines
reportedAugust: FDA
approves
Pfizer (≥16y)
October:
EUA Pfizer
5-11y January: FDA
approves
Moderna
(≥18y) May 2022: Janssen
vaccine no longer
recommendedJune: EUA Pfizer (6m –4y),
Moderna (6m –17y)
July: EUA
Novavax
vaccine (≥18y)2020
Primary
Series
Monovalent
Boosters
Bivalent mRNA
Boosters
VSD COVID -19 RCA
Safety Publications2021 2022 2023
March: >200
million doses
given in US
by the end
AprilApril:
Janssen
and CVST
concernsFebruary:
Janssen
EUA
(≥18y)
June : mRNA
vaccine safety
6m-5y (Pediatrics )July: FDA
safety
warning re:
GBS and
Janssen.
34Primary Series uptake among persons aged 5 -11 years in the VSD, over time*
* Data through
February 4,
2023426,177
3,122450,217
2,256
Summary of RCA Findings in the 1 -21 Day Risk Interval, 5 –11-year-olds
Compared with Outcome Events 22 -42 days after in Vaccinated Comparators*
Outcome Both
Event Doses
1 -21 Appendicitis No No No
Bell's palsy No No No
Encephalitis / myelitis / encephalomyelitis No No No
Stroke, hemorrhagic No No No
Stroke, ischemic No - No
Immune thrombocytopenia No No No
Kawasaki disease No No No
Myocarditis / pericarditis No No No
Seizures No No No
Thrombotic thrombocytopenic purpura No - NoPfizer
Risk
Interval
DaysDose 1 Dose 2
➢Among children aged 5 -11 years in the VSD, no outcome met the signaling criteria in the
21 days after primary series vaccination.Signal?** Signal?**
*Final analyses through January 2023
**Signaling threshold P<0.061 (one -sided)
36

37September: Interim mRNA vaccines safety
surveillance, including myocarditis/pericarditis risk
(JAMA )September:
Bivalent boosters
Pfizer (≥12y) and
Moderna (≥18y)September: Bivalent
boosters. Monovalent
boosters discontinuedMay: Pfizer
monovalent
booster 5 -
11yMarch: 2nd
monovalent
booster
(≥50y)January:
Pfizer
monovalent
booster
12-15ySeptember/October:
Adult monovalent
booster; Pfizer
(≥16y), Moderna and
Janssen (≥18y)
October: Myocarditis/pericarditis
rates after primary and monovalent
boosters <40y ( Ann Int Med )August: Risk of myocarditis/
pericarditis Pfizer vs Moderna
(Vaccine )April: GBS following
Janssen vaccine ( JAMA
Network Open )December:
EUA Moderna
(≥18y) and
Pfizer (≥16y)
November/December: first
VSD signal, ischemic stroke
after bivalent Pfizer ≥65y
October:
Bivalent
boosters Pfizer
(5-11y) and
Moderna (6 -17y)December:
Bivalent boosters
Pfizer (6m -4y) and
Moderna (6m -5y)May: EUA
Pfizer 12 -
15y
May:
myocarditis/
pericarditis
after mRNA
vaccines
reportedAugust: FDA
approves
Pfizer (≥16y)
October:
EUA Pfizer
5-11y January: FDA
approves
Moderna
(≥18y) May 2022: Janssen
vaccine no longer
recommendedJune: EUA Pfizer (6m –4y),
Moderna (6m –17y)
July: EUA
Novavax
vaccine (≥18y)2020
Primary
Series
Monovalent
Boosters
Bivalent mRNA
Boosters
VSD COVID -19 RCA
Safety Publications2021 2022 2023
March: >200
million doses
given in US
by the end
AprilApril:
Janssen
and CVST
concernsFebruary:
Janssen
EUA
(≥18y)
June : mRNA
vaccine safety
6m-5y (Pediatrics )July: FDA
safety
warning re:
GBS and
Janssen.
38Monovalent Booster Uptake Among Persons Aged5-11 Years in the VSD, Over Time*
* Data through September 10, 2022

Summary of RCA Findings in the 1 -21 Day Risk Interval after Monovalent Booster, 5 –11-year-olds
Compared with Outcome Events 22 -42 days after in Vaccinated Comparators*
➢Among children aged 5 -11 years in the VSD, no outcome met the signaling criteria in the
21 days after monovalent booster vaccination. However, vaccine uptake was low.
Signal?**
*Final analyses through January 2023
**Signaling threshold P<0.011 (one -sided)
40September: Interim mRNA vaccines safety
surveillance, including myocarditis/pericarditis risk
(JAMA )September:
Bivalent boosters
Pfizer (≥12y) and
Moderna (≥18y)September: Bivalent
boosters. Monovalent
boosters discontinuedMay: Pfizer
monovalent
booster 5 -
11yMarch: 2nd
monovalent
booster
(≥50y)January:
Pfizer
monovalent
booster
12-15ySeptember/October:
Adult monovalent
booster; Pfizer
(≥16y), Moderna and
Janssen (≥18y)
October: Myocarditis/pericarditis
rates after primary and monovalent
boosters <40y ( Ann Int Med )August: Risk of myocarditis/
pericarditis Pfizer vs Moderna
(Vaccine )April: GBS following
Janssen vaccine ( JAMA
Network Open )December:
EUA Moderna
(≥18y) and
Pfizer (≥16y)
November/December: first
VSD signal, ischemic stroke
after bivalent Pfizer ≥65y
October:
Bivalent
boosters Pfizer
(5-11y) and
Moderna (6 -17y)December:
Bivalent boosters
Pfizer (6m -4y) and
Moderna (6m -5y)May: EUA
Pfizer 12 -
15y
May:
myocarditis/
pericarditis
after mRNA
vaccines
reportedAugust: FDA
approves
Pfizer (≥16y)
October:
EUA Pfizer
5-11y January: FDA
approves
Moderna
(≥18y) May 2022: Janssen
vaccine no longer
recommendedJune: EUA Pfizer (6m –4y),
Moderna (6m –17y)
July: EUA
Novavax
vaccine (≥18y)2020
Primary
Series
Monovalent
Boosters
Bivalent mRNA
Boosters
VSD COVID -19 RCA
Safety Publications2021 2022 2023
March: >200
million doses
given in US
by the end
AprilApril:
Janssen
and CVST
concernsFebruary:
Janssen
EUA
(≥18y)
June : mRNA
vaccine safety
6m-5y (PediatricsJuly: FDA
safety
warning re:
GBS and
Janssen.
41Primary Series Uptake Among Persons Aged≥12 Years in the VSD, Over Time*
* Data through May 21, 2022Dose 1 Dose 2 Total
Pfizer 4,669,621 4,558,067 9,227,688
Moderna 3,014,353 2,951,499 5,965,852
Janssen 511,944 NA 511,944
Total 8,195,918 7,509,566 15,705,484
Final RCA Findings in the 1 -21 Day Risk Interval After Primary Series ≥12 Years
Compared with Outcome Events 22 -42 days after in Vaccinated Comparators*
*Final analyses through May 2022
**Signaling threshold P<0.01 (one -sided)Signal?** Signal?** Signal?** Signal?** Signal?** Signal?** Signal?**
43September: Interim mRNA vaccines safety
surveillance, including myocarditis/pericarditis risk
(JAMA )September:
Bivalent boosters
Pfizer (≥12y) and
Moderna (≥18y)September: Bivalent
boosters. Monovalent
boosters discontinuedMay: Pfizer
monovalent
booster 5 -
11yMarch: 2nd
monovalent
booster
(≥50y)January:
Pfizer
monovalent
booster
12-15ySeptember/October:
Adult monovalent
booster; Pfizer
(≥16y), Moderna and
Janssen (≥18y)
October: Myocarditis/pericarditis
rates after primary and monovalent
boosters <40y ( Ann Int Med )August: Risk of myocarditis/
pericarditis Pfizer vs Moderna
(Vaccine )April: GBS following
Janssen vaccine ( JAMA
Network Open )December:
EUA Moderna
(≥18y) and
Pfizer (≥16y)
November/December: first
VSD signal, ischemic stroke
after bivalent Pfizer ≥65y
October:
Bivalent
boosters Pfizer
(5-11y) and
Moderna (6 -17y)December:
Bivalent boosters
Pfizer (6m -4y) and
Moderna (6m -5y)May: EUA
Pfizer 12 -
15y
May:
myocarditis/
pericarditis
after mRNA
vaccines
reportedAugust: FDA
approves
Pfizer (≥16y)
October:
EUA Pfizer
5-11y January: FDA
approves
Moderna
(≥18y) May 2022: Janssen
vaccine no longer
recommendedJune: EUA Pfizer (6m –4y),
Moderna (6m –17y)
July: EUA
Novavax
vaccine (≥18y)2020
Primary
Series
Monovalent
Boosters
Bivalent mRNA
Boosters
VSD COVID -19 RCA
Safety Publications2021 2022 2023
March: >200
million doses
given in US
by the end
AprilApril:
Janssen
and CVST
concernsFebruary:
Janssen
EUA
(≥18y)
June : mRNA
vaccine safety
6m-5y (Pediatrics )July: FDA
safety
warning re:
GBS and
Janssen.
44Primary Series Uptake Among Persons Aged6 Months -5 Years in the VSD,
Over Time*
* Data through March 18, 2023Dose 1 Dose 2 Dose 3 Total
Pfizer 70,580 62,452 30,641 163,673
Moderna 59,872 52,134 NA 112,006
Total 130,452 114,586 30,641 275,679
45RCA in the 1 -21 Day Risk Interval, 6 months -4/5-year-olds
Compared with Outcome Events 22 -42 days after in Vaccinated Comparators on the Same Calendar Days, June 18, 2022 –March 18, 2023
Goddard K, Donahue JG, Lewis N, Hanson KE, Weintraub ES, Fireman B, Klein NP. Safety of COVID -19 mRNA Vaccination Among Young Ch ildren in the Vaccine Safety Datalink. Pediatrics. 2023 Jul 1;152(1):e2023061894. doi: 10.1542/peds.2023 -061894.
46RCA in the 1 -21 Day Risk Interval, 6 months -4/5-year-olds
Compared with Outcome Events 22 -42 days after in Vaccinated Comparators on the Same Calendar Days, June 18, 2022 –March, 2023
Goddard K, Donahue JG, Lewis N, Hanson KE, Weintraub ES, Fireman B, Klein NP. Safety of COVID -19 mRNA Vaccination Among Young Ch ildren in the Vaccine Safety Datalink. Pediatrics. 2023 Jul 1;152(1):e2023061894. doi: 10.1542/peds.2023 -061894.•Among children 6 month -4/5 years, no outcome met the signaling
criteria in the 21 days after primary series.
•No cases of myocarditis or pericarditis within the risk interval
•However, vaccine uptake has been low
47September: Interim mRNA vaccines safety
surveillance, including myocarditis/pericarditis risk
(JAMA )September:
Bivalent boosters
Pfizer (≥12y) and
Moderna (≥18y)September: Bivalent
boosters. Monovalent
boosters discontinuedMay: Pfizer
monovalent
booster 5 -
11yMarch: 2nd
monovalent
booster
(≥50y)January:
Pfizer
monovalent
booster
12-15ySeptember/October:
Adult monovalent
booster; Pfizer
(≥16y), Moderna and
Janssen (≥18y)
October: Myocarditis/pericarditis
rates after primary and monovalent
boosters <40y ( Ann Int Med )August: Risk of myocarditis/
pericarditis Pfizer vs Moderna
(Vaccine )April: GBS following
Janssen vaccine ( JAMA
Network Open )December:
EUA Moderna
(≥18y) and
Pfizer (≥16y)
November/December: first
VSD signal, ischemic stroke
after bivalent Pfizer ≥65y
October:
Bivalent
boosters Pfizer
(5-11y) and
Moderna (6 -17y)December:
Bivalent boosters
Pfizer (6m -4y) and
Moderna (6m -5y)May: EUA
Pfizer 12 -
15y
May:
myocarditis/
pericarditis
after mRNA
vaccines
reportedAugust: FDA
approves
Pfizer (≥16y)
October:
EUA Pfizer
5-11y January: FDA
approves
Moderna
(≥18y) May 2022: Janssen
vaccine no longer
recommendedJune: EUA Pfizer (6m –4y),
Moderna (6m –17y)
July: EUA
Novavax
vaccine (≥18y)2020
Primary
Series
Monovalent
Boosters
Bivalent mRNA
Boosters
VSD COVID -19 RCA
Safety Publications2021 2022 2023
March: >200
million doses
given in US
by the end
AprilApril:
Janssen
and CVST
concernsFebruary:
Janssen
EUA
(≥18y)
June : mRNA
vaccine safety
6m-5y (PediatricsJuly: FDA
safety
warning re:
GBS and
Janssen.
48Bivalent Booster Uptake Among Persons Aged ≥12 Years, Over Time*
* Data through March 18, 2023
Pfizer -BioNTech
Moderna1,855,946
851,807
Summary RCA Findings in the 1 -21 Day Risk Interval after Bivalent Booster 6 months -64 years
Compared with Outcome Events 22 -42 days after in Vaccinated Comparators*
*Analyses through March 2023
**Signaling threshold P<0.01 (one -sided)Signal?** Signal?**Risk Interval
DaysAge GroupOutcomeEither mRNA Pfizer ModernaEvent
1 -21 0-4y Kawasaki disease No No -
5-11y Appendicitis No No -
Bell's palsy No No -
Stroke, hemorrhagic No No -
Immune thrombocytopenia No No -
Seizures No No -
12-17y Appendicitis No No No
Bell's palsy No No -
Encephalitis / myelitis / encephalomyelitis No No -
Immune thrombocytopenia No No -
Seizures No No -
Venous thromboembolism No No -
18-64y Acute disseminated encephalomyelitis No No -
Acute myocardial infarction No No No
Appendicitis No No No
Bell's palsy No No No
Cerebral venous sinus thrombosis No No No
Disseminated intravascular coagulation No - No
Encephalitis / myelitis / encephalomyelitis No No No
Guillain -Barre syndrome No No -
Stroke, hemorrhagic No No No
Stroke, ischemic No No No
Immune thrombocytopenia No No No
Myocarditis / pericarditis No No No
Seizures No No No
Transverse myelitis No No -
Thrombotic thrombocytopenic purpura No No No
Thrombosis with thrombocytopenia syndrome No No No
Venous thromboembolism No No No
Pulmonary embolism (subset of VTE) No No No➢Among ages 5 -64 years in
the VSD, no outcomes have
met the signaling criteria in
the 21 days after bivalent
booster vaccine.
50VSD Incidence Rates of Verified Myocarditis or Pericarditis in the 0 –7
Days After Bivalent Booster in Ages 12 –39 years*
Dose 2 primary series
Pfizer -BioNTechMonovalent booster dose
Pfizer -BioNTechBivalent Booster Doses
(Pfizer and Moderna)
Age Group
(yrs)Cases Total
Dose 2 (N)Incidence rate/
million doses
(95% CI)Cases Total
Doses
(N)Incidence rate/
million doses
(95% CI)Cases Total Doses
(N)Incidence rate/
million doses
(95% CI)
Pfizer
12–17
Males
Females45
6308,046
311,247146.1 (106.6 –195.5)
19.3 (7.1 –42.0)14
2129,487
139,118108.1 (59.1 –181.4)
14.4 (1.7 –51.9)0
055,649
57,7760.0 (0.0 –53.8)
0.0 (0.0 –51.9)
18–29
Males
Females27
2331,889
400,32181.4 (53.6 –118.4)
5.0 (0.6 –18.0)7
1166,973
240,22641.9 (16.9 –86.4)
4.2 (0.1 –23.2)1
060,338
95,16216.6 (0.4 –92.3)
0.0 (0.0 –31.5)
30–39
Males
Females5
3341,527
410,71314.6 (4.8 –34.2)
7.3 (1.5 –21.3)3
1197,554
268,41215.2 (3.1 –44.4)
3.7 (0.1 –20.8)0
097,171
133,3050.0 (0.0 –30.8)
0.0 (0.0 –22.5)
Moderna
18–29
Males
Females19
0195,809
243,56097.0 (58.4 –151.5)
0.0 (0.0 –12.3)7
1109,337
156,70764.0 (25.7 –131.9)
6.4 (0.2 –35.6)0
022,247
35,3930.0 (0.0 –134.7)
0.0 (0.0 –84.6)
30–39
Males
Females8
1216,583
259,78036.9 (15.9 –72.8)
3.9 (0.1 –21.4)1
2149,468
191,7656.7 (0.2 –37.3)
10.4 (1.3 –37.7)1
041,820
55,81623.9 (0.6 –133.2)
0.0 (0.0 –53.7)
* Primary series and monovalent booster data through August 20, 2022; ; source: Goddard K, et al. Incidence of Myocarditis/Pericarditis Following mRNA COVID -19 Vaccination Among Children and
Younger Adults in the United States .Ann Intern Med. 2022;175:1169 -1771 .Bivalent booster data through March 11, 2023
51September: Interim mRNA vaccines safety
surveillance, including myocarditis/pericarditis risk
(JAMA )September:
Bivalent boosters
Pfizer (≥12y) and
Moderna (≥18y)September: Bivalent
boosters. Monovalent
boosters discontinuedMay: Pfizer
monovalent
booster 5 -
11yMarch: 2nd
monovalent
booster
(≥50y)January:
Pfizer
monovalent
booster
12-15ySeptember/October:
Adult monovalent
booster; Pfizer
(≥16y), Moderna and
Janssen (≥18y)
October: Myocarditis/pericarditis
rates after primary and monovalent
boosters <40y ( Ann Int Med )August: Risk of myocarditis/
pericarditis Pfizer vs Moderna
(Vaccine )April: GBS following
Janssen vaccine ( JAMA
Network Open )December:
EUA Moderna
(≥18y) and
Pfizer (≥16y)
November/December: first
VSD signal, ischemic stroke
after bivalent Pfizer ≥65y
October:
Bivalent
boosters Pfizer
(5-11y) and
Moderna (6 -17y)December:
Bivalent boosters
Pfizer (6m -4y) and
Moderna (6m -5y)May: EUA
Pfizer 12 -
15y
May:
myocarditis/
pericarditis
after mRNA
vaccines
reportedAugust: FDA
approves
Pfizer (≥16y)
October:
EUA Pfizer
5-11y January: FDA
approves
Moderna
(≥18y) May 2022: Janssen
vaccine no longer
recommendedJune: EUA Pfizer (6m –4y),
Moderna (6m –17y)
July: EUA
Novavax
vaccine (≥18y)2020
Primary
Series
Monovalent
Boosters
Bivalent mRNA
Boosters
VSD COVID -19 RCA
Safety Publications2021 2022 2023
March: >200
million doses
given in US
by the end
AprilApril:
Janssen
and CVST
concernsFebruary:
Janssen
EUA
(≥18y)
June : mRNA
vaccine safety
6m-5y (PediatricsJuly: FDA
safety
warning re:
GBS and
Janssen.
Ischemic Stroke Following Pfizer Bivalent
Booster Vaccination in 65+ Years of Age
52
53Number of COVID -19 Bivalent Booster Doses and Influenza Vaccine Doses
Administered Over Time Among Persons Aged ≥65 years, by Vaccine Type

Risk Interval Days Age GroupOutcomeEither mRNA Pfizer ModernaEvent
1 -21 65+ Acute myocardial infarction No No No
Appendicitis No No No
Bell's palsy No No No
Cerebral venous sinus thrombosis No No -
Disseminated intravascular coagulation No No No
Guillain -Barre syndrome No No No
Stroke, hemorrhagic No No No
Stroke, ischemic Yes Yes No
Immune thrombocytopenia No No No
Myocarditis / pericarditis No No No
Seizures No No No
Thrombotic thrombocytopenic purpura No No No
Thrombosis with thrombocytopenia syndrome No No No
Venous thromboembolism No No No
Pulmonary embolism (subset of VTE) No No NoSummary RCA Findings in the 1 -21 Day Risk Interval After Bivalent Booster ≥65 years
Compared with Outcome Events 22 -42 days after in Vaccinated Comparators*
*Analyses through March 2023
**Signaling threshold P<0.01 (one -sided)Signal?** Signal?**
➢Ischemic stroke signaled in the 21 days after bivalent booster vaccine among ≥65 years in the VSD.Signal?**
55Ischemic Stroke AfterPfizer -BioNTech Bivalent Booster , Age ≥65 years,
Counts and Adjusted Rate Ratios (Oct 15, 2022 –March 18 , 2023)
Red dot represents sequential signal: p -value <0.01 (1 -sided)RR= 1.25 (95% CI 0.98 –1.59)
56Ischemic Stroke by Day after Pfizer -BioNTech Bivalent
Booster, People Aged ≥65 Years*
Cluster days 13 –22, p -value = 0.0637
*Data cutoff 2/28/2023
57Post -Signal analyses*:
Ischemic Stroke Incidence During Days 1 –21 Compared with Days 22 –42,
Among ≥65 Years With and Without Simultaneous Influenza Vaccination
Analytic populationCases in 1 –21-day
Risk Interval
(N=139)Cases in 22 –42-day
Comparison Interval
(N=108)Adjusted
Rate Ratio**
(95% CI)P-value
Bivalent Pfizer + same -day
high-dose or adjuvanted
flu vaccine43 27 1.59 (0.99 –2.61) 0.06
Bivalent Pfizer + same day
standard dose flu vaccine8 11 0.73 (0.28 -1.83) 0.50
Bivalent Pfizer without any
same day flu vaccine107 99 1.08 (0.82 –1.42) 0.58
* Analyses only include vaccination data through January 14, 2023, and stroke outcome data through February 25, 2023
** Adjusted by 5 -year age groups
58

59Additional Considerations for Stroke Outcome
▪Small numbers of strokes and imprecise rate ratios limit some analyses
•Uptake of Moderna booster was delayed and reduced due to distribution delays
•Follow -up of individuals concurrently given bivalent booster + hi -dose flu was limited by small numbers
▪Difficult to interpret temporal clustering which attenuated as rate ratio attenuated
▪Possible unmeasured confounding
•Results may be influenced by confounders that vary over time
•Do early adopters of bivalent booster vaccine have greater risk of near -term cardiovascular events?
‒Same trend has not been observed for acute myocardial infarctions
‒Potential impact of differential vaccine availability after EUA (Pfizer -BioNTech > Moderna)
▪Possible role of SARS -CoV-2 infection before booster?
•Background incidence of SARS -CoV-2 infection was rapidly changing during bivalent booster uptake
‒Analysis excluded cases with COVID -19 diagnosis or positive test in prior 30 days, although asymptomatic
infections and home antigen tests are not consistently documented in EHR; however, KPNC chart reviews did not
find recent SARS -CoV-2 infection or exposure
Anaphylaxis
•The rate of anaphylaxis was ~ 5 cases/million doses for the mRNA primary series.
̶The rate of anaphylaxis was <5 cases/million doses for mRNA booster doses.
Myocarditis/Pericarditis after mRNA vaccines
•During days 0 -7 post vaccination , both mRNA vaccines were associated with increased risk of
myocarditis/pericarditis in 12 –39-year-olds.
•Risk estimates of myocarditis/pericarditis in 18 –39-year-olds during days 0 -7 after 2 doses were
modestly higher after Moderna than after Pfizer.
•For persons ages 12 –39 years, rates of myocarditis/pericarditis 0 –7 days after primary and
monovalent boosters were highest among male 12 -15 and 16 –17-year-olds.
̶Evidence suggests there was an increased risk for myocarditis/pericarditis following monovalent booster dose for
some age groups.
̶No current evidence for an increased rate of myocarditis/pericarditis following bivalent boosters. Uptake was low in
age groups expected to be at highest risk. Summary of Safety Findings after COVID -19 Vaccines in the VSD
60
Ischemic stroke after Pfizer bivalent booster
•Rate ratio met signaling criteria consistently for 8 weeks but slowly attenuated and now
does not meet signaling criteria
•Temporal clustering 13 –22 days after vaccination (significant at time of initial signal but
attenuated as the rate ratio estimate attenuated)
•Supplemental analyses using un -boosted concurrent comparators showed a rate ratio
RR=1.07 (95% CI 0.89 –1.28) (data not shown)
•Analyses evaluating simultaneous high -dose or adjuvanted flu vaccine showed a rate ratio
RR=1.59 ( 95% CI 0.99 –2.61)
̶Separate analyses did not detect an elevated RR for stroke after flu vaccine alone (data not shown)
GBS after Janssen vaccine
•Findings were consistent withanassociation between increased riskofGBS andJanssen
COVID -19vaccine.
61Summary of Safety Findings After COVID -19 Vaccines in the VSD
Summary of VSD COVID RCA chart review
62Vaccine Outcome
Acute
disseminated
encephalo -
myelitis
(ADEM)
N=9Anaphylaxis
N=342Cerebral
venous sinus
thrombosis
(CVST)
N=98Guillain -
Barré
syndrome
(GBS)
N=130Ischemic
Stroke
N=100Multisystem
Inflammatory
Syndrome –
Child/Adult
(MIS -C/A)
N=33Myocarditis/
Pericarditis
N=935Thrombosis
with
thrombo -
cytopenia
syndrome
(TTS)
N=32Transverse
myelitis
(TM)
N=43Venous
thrombo -
embolism
(VTE)
N=186TOTAL
N=1908
Primary
series
(mRNA and
Janssen)9 300 98 130 NR 33 342
(6 months -
39 yrs)32 43 186 1173
Monovalent
Booster
(mRNA) NR 30 NR NR NR NR 362
(all ages)NR NR NR 392
Bivalent
Booster
(mRNA)NR 12 NR NR 100
(65+ yrs)NR 231
(all ages)NR NR NR 343
*Counts are included per individual; however, most outcomes underwent multiple reviews (i.e., quick review, full review, clin ical
adjudication)
NR= not reviewed
1.Vaccine uptake was early & unpredictable.
̶One rationale for using vaccinated concurrent comparators.
̶Most RCA findings came early and have been mostly unchanged since fall 2021.
2.The VSD COVID -19 RCA analytic methods have been hard to understand.
̶We believe that vaccinated concurrent comparators are less vulnerable to bias, but it is an unfamiliar approach that
is difficult to explain how the follow up in the comparison interval is concurrent (i.e., on the same calendar day) with
the follow up in the risk interval.
̶However, intense public attention on COVID vaccine safety meant we frequently communicated preliminary results
on short notice, and methods that are hard to concisely explain and understand posed substantial challenges.
3.Our vaccine safety questions have frequently changed and expanded, requiring us to rapidly
adapt our surveillance to include new outcomes and age groups.
̶Flexibility in routinely accommodating (sometime substantial) changes has been critical.
4.Challenging to digest and interpret the large amounts of potentially relevant data and results
that we put “on the shelf” weekly (e.g., comparisons with unvaccinated people).
̶Supplementary analyses were available should a safety concern arise from VSD or elsewhere. 63Challenges in Rapidly Generating Vaccine Safety Evidence
During the Pandemic
•2020 -2023 VSD COVID -19 RCA surveillance is complete.
•Future Studies -VSD may consider further investigating:
•mRNA vaccine primary series signals of VTE and AMI
•Bell’s palsy after Janssen primary and mRNA monovalent booster (limited
data since neither vaccine is currently available or used)
•Ischemic stroke after concomitant bivalent boosters and flu vaccines in ≥65 -
year-olds in future season
64Future Considerations
It takes a village…
65
•Kaiser Permanente Northern California:
•Ned Lewis, Kristin Goddard, Bruce Fireman, Ousseny Zerbo, Karen Nunley, Pat Ross, Nandini Bahkshi , Laurie
Aukes, Berwick Chan, Arnold Yee, Varun Shah
•Marshfield Clinic Research Institute:
•Jim Donahue, Kayla Hanson, Ed Belongia, Tom Boyce, Burney Kieke, Dave McClure, Erica Scotty
•CDC Immunization Safety Office:
•Eric Weintraub, Tom Shimabukuro, Matt Oster, Tat’Yana Kenigsberg, Jonathan Duffy, Frank Destefano, Tanya
Myers
•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, ColoradoAcknowledgements
66

Summary: COVID -19 Vaccine Safety Surveillance: Summary from VSD RCA Nicola Klein, MD, PhD Director, Kaiser Permanente Vaccine Study Center Kaiser Permanente Northern California Advisory Committee in Immunization Practices September 12, 2023  2Vaccine Safety Datalink •Active surveillance: newly licensed vaccines ̶Rapid Cycle Analysis (RCA)  •Evaluate vaccine safety: ̶of new recommendations for existing vaccines ̶for vaccines in high -risk populations, particularly pregnant women  (+ other groups)…


08 COVID Priddy 508

1
Safety and Immunogenicity of Moderna COVID -19
Vaccine (2023 -2024 Formula)
Monovalent XBB.1.5 Variant Vaccine
ACIP
September 12, 2023
Frances Priddy, MD MPH
Moderna
2
Outline of Presentation
▪Overview of clinical trial of XBB.1.5 vaccine
▪Design
▪Safety data
▪Immunogenicity data
▪Analysis of cross neutralization data for recent variants
▪Summary
3
Phase 2/3 Randomized Safety and Immunogenicity Study
of XBB.1.5 -Containing Booster in Adults ≥18 Years
https://clinicaltrials.gov/ct2/show/NCT04927065▪Participants previously received 4 doses of COVID -19 vaccine (primary series and booster of
mRNA -1273 + booster of BA.4/BA.5 vaccine)
▪Focus of today's presentation will be on the monovalent XBB.1.5 vaccine selected for
2023 -2024 season
▪All analyses are descriptive
+Randomized
April 25 -27,
2023
N = 101 50 µg XBB.1.5
25 µg BA.4/5
25 µg XBB.1.5N = 51N = 50
Bivalent
BA.4/5 + XBB.1.5
50 μg Monovalent
XBB.1.5
50 μg
4
Demographics and Baseline Characteristics
Study 205J, XBB.1.5 Recipients
CharacteristicMonovalent
XBB.1.5
N = 50
Mean Age – Years 51.6
Median Age – Years (range) 55 (21, 84)
≥ 65 years 11 (22.0%)
% Female 30 (60.0%)
Non-White Race 5 (10.0%)
Months between 2nd and 3rd Dose, median (Q1, Q3) 8.2 (7.8, 9.8)
Months between 3rd and 4th Dose , median (Q1, Q3) 9.8 (8.3, 10.3)
Months between 4th and 5th Dose, median (Q1, Q3) 8.2 (8.1, 8.3)
Prior SARS -CoV-2 Infection 34 (68.0%)5th Dose (3rd Booster)
5
Safety of Moderna COVID -19 Vaccine
(2023 -2024 Formula)
XBB.1.5 Monovalent Vaccine
6
Within 7 days of injection ; No Grade 4 events reported
Chalkias et al., medRxiv, 2022, Chu et al, Nat Med 28:1041, 2022 Local Reactions Following Booster Doses in Adults
Study 205J and Study 205H, Solicited Safety Set
Participants
(%)68%84% 82%
4% 5% 5%10%5%8%16%20% 21%
0%25%50%75%100%
Mono
XBB.1.5Original Bivalent
BA.4/5Mono
XBB.1.5Original Bivalent
BA.4/5Mono
XBB.1.5Original Bivalent
BA.4/5Mono
XBB.1.5Original Bivalent
BA.4/5Pain Erythema Swelling Axillary Swelling
or TendernessGrade 3 Grade 1 -2Original Vaccine
N = 167Monovalent XBB.1.5
N = 50Bivalent BA.4/BA.5
N = 508
Local reactions similar or lower than previously authorized Moderna COVID -19 vaccines
7
Systemic Reactions Following Booster Doses in Adults
Study 205J and Study 205H, Solicited Safety Set
Within 7 days of injection ; No Grade 4 events reported
Chalkias et al., medRxiv, 2022, Chu et al, Nat Med 28:1041, 2022 Grade 3 Grade 1 -2Original Vaccine
N = 167Monovalent XBB.1.5
N = 50Bivalent BA.4/BA.5
N = 508
6% 7%4%34%55%
49%44%59% 60%
38%49%46%
28%41%
35%
8%11%14% 14%35%
22%
0%25%50%75%100%
Participants
(%)
Headache Fatigue Myalgia Arthralgia Nausea /
VomitingChills Fever
≥ 38.0ºC (≥100.4ºF)
Systemic reactions similar or lower than previously authorized Moderna COVID -19 vaccines
8
Immunogenicity of  Moderna COVID -19
Vaccine (2023 -2024 Formula)
XBB.1.5 Monovalent Vaccine
9
Rapid Assessment of Neutralization Capacity of
2023 -2024 XBB.1.5 Vaccine Against Emerging Variants
▪Pre and post booster sera from XBB.1.5 vaccine recipients assessed against
previously dominant and newly emerged variants
▪Duke assay (Lenti -PsVNA) – Day 29 sera assessed
▪Moderna research assay (VSV -PsVNA) – Day 15 sera assessed
▪Titers generally consistent between Day 15 and Day 29

▪Sera tested against:
▪Prior strains:    Ancestral (D614G), BA.4/BA.5
▪XBB-lineage:   XBB.1.5, XBB.1.16
▪New strains:    EG.5.1, FL.1.5.1, BA.2.86
PsVNA – pseudovirus neutralization assay; VSV – vesicular stomatitis virus
Chalkias et al. medRxiv  2023 https://doi.org/10.1101/2023.08.22.23293434
Correlation between Duke and Moderna assay described in Choi et al, Nature Medicine https://doi.org/10.1038/s41591 -021-01527 -y
10
155221
7410427113694
1042 1077
110100100010000100000
XBB.1.5 XBB.1.16 EG.5.1 BA.2.86Cross Neutralization Results (Day 29) After XBB.1.5 Vaccine  in
Adults – Duke Assay
Study 205J, Per -Protocol Immunogenicity Set - All Participants
Neutralizing
Antibody
Titer (ID50)
14.0-fold riseEG.5.1
16.7-fold riseXBB.1.16Day 29 Pre-Boost
Substantial f old rise  demonstrated across newer variants
17.5-fold riseXBB.1.5
Day 29 Pre-Boost
Pseudovirus neutralization assay
10.4-fold riseBA.2.86
Day 29 Pre-Boost Day 29 Pre-Boost Day 29 Pre-Boost
11
Cross Neutralization Results (Day 29) After XBB.1.5 Vaccine in
Adults by Baseline SARS -CoV-2 Serostatus  - Duke Assay
Study 205J, Per -Protocol Immunogenicity Set
Cross neutralization demonstrated regardless of prior SARS -CoV-2 infection
Pseudovirus neutralization assay82 134
43 6015432246
628 726
1101001000100001000001000000
1 2 3 4
211 27496 1353562 4702
1331 1304
1101001000100001000001000000
1 2 3 4Neutralizing
Antibody
Titer (ID50)
Neutralizing
Antibody
Titer (ID50)
D29 PB
No Prior Infection
Prior Infection
14.6-fold riseEG.5.1
13.9-fold rise
16.7-fold riseXBB.1.16
17.2-fold riseDay 29 Pre-Boost
18.8-fold riseXBB.1.5
16.9-fold rise
13.1-fold riseBA.2.86
9.3-fold rise
D29 PB D29 PB D29 PB
12
116144 118931621207 1393 126410571406
110100100010000100000
1 2 3 4 5Cross Neutralization Results (Day 15) After XBB.1.5 Vaccine in
Adults - Moderna Assay
Study 205J, Subset Analysis (N = 20)
Consistent c ross neutralization demonstrated for newer variants, including BA.2.86
Pseudovirus neutralization assay; PB - pre boostNeutralizing
Antibody
Titer (ID50)
D15 PB
10.7-fold riseEG.5.1
8.7-fold riseBA.2.86
11.4-fold riseFL.1.5.1
9.7-fold riseXBB.1.16
10.4-fold riseXBB.1.5
D15 PB D15 PB D15 PB D15 PBDay 15 Pre-Boost
13
159 190 142 1322961259 1676 14991157 1600
1101001000100001000001000000
1 2 3 4 585 109 9765 8811581158 1065 964 1237
1101001000100001000001000000
1 2 3 4 5Neutralizing
Antibody
Titer (ID50)
Neutralizing
Antibody
Titer (ID50)
D15 PB
No Prior Infection
Prior InfectionCross Neutralization Results (Day 15) After XBB.1.5 Vaccine in
Adults by Baseline SARS -CoV-2 Serostatus  - Moderna Assay
Study 205J, Subset Analysis (N=20)
11-fold riseEG.5.1
10.5-fold rise
14-fold riseBA.2.86
5.4-fold rise
14.8-fold riseFL.1.5.1
8.8-fold rise
10.6-fold riseXBB.1.16
8.8-fold rise
13.6-fold riseXBB.1.5
7.9-fold rise
D15 PB D15 PB D15 PB D15 PB
Cross neutralization demonstrated regardless of prior SARS -CoV-2 infectionDay 15 Pre-Boost
Pseudovirus neutralization assay
14
1151
123
162417139961
3355
298468
276148
110100100010000100000
1 2 3 4 5 6Cross Neutralization Results (Day 29) in Adults after Bivalent
BA.4/BA.5 Vaccine
Study 205H – Duke Assay
Neutralizing
Antibody
Titer (ID50)Day 29 Pre-Boost
Ancestral
8.7-fold riseBA.4/BA.5
27.3-fold riseXBB.1.5
12.3-fold riseXBB.2.3.2
15.8-fold riseEG.5
11.6- fold riseXBB.1.16
19.3-fold rise
D29 PB
Limited cross neutralization to newer variants after previously authorized BA.4/BA.5 bivalent vaccineD29 PB D29 PB D29 PB D29 PB D29 PB
Pseudovirus neutralization assay; PB - pre boost
15
Summary
Safety and Immunogenicity of Moderna COVID -19 Vaccine (2023 -2024 Formula)
XBB.1.5 Vaccine
Moderna’s
Vaccine
PreparednessClinical Study
of XBB.1.5
Vaccine
▪Moderna will supply an XBB.1.5  vaccine  for Fall 2023
▪Moderna will continue its ongoing variant monitoring and risk
assessment of emerging variants▪Safety profile of XBB.1.5 vaccine consistent with previously authorized
vaccines
▪Robust neutralizing antibody titers against XBB.1.5, XBB.1.16, EG.5.1,
FL.1.5.1, and BA.2.86 measured in sera from recipients of XBB.1.5
vaccine
▪XBB.1.5 vaccine is anticipated to be effective against current
SARS -CoV-2 variants
16
THANK YOU to Our Study Collaborators,
Investigators, and Participants
▪All investigators
▪Study site personnel
▪Laboratory personnel
▪Most importantly, the individuals who participated in these trials

Summary: 1 Safety and Immunogenicity of Moderna COVID -19  Vaccine (2023 -2024 Formula) Monovalent XBB.1.5 Variant Vaccine ACIP September 12, 2023 Frances Priddy, MD MPH Moderna 2 Outline of Presentation ▪Overview of clinical trial of XBB.1.5 vaccine ▪Design  ▪Safety data ▪Immunogenicity data ▪Analysis of cross neutralization data for recent variants ▪Summary 3 Phase 2/3 Randomized Safety and Immunogenicity Study  of XBB.1.5 -Containing Booster in Adults ≥18 Years…


09 COVID Dubovsky 508

Data in Support of Novavax XBB.1.5 Vaccine
Dr. Filip Dubovsky , President, Research & Development
September 12, 2023
1
Novavax Vaccine Platform: Recombinant Protein
Particle Plus Matrix -M™ Adjuvant
2Recombinant protein particle
Native 3-dimensional conformation
Truncated S. frugiperda glycans
Particulate structure facilitates antigen
presentation and processing
Novavax
2023- 2024 vaccine
Matrix -M adjuvant
Induces robust neutralizing antibodies
Induces polyfunctional CD4+ Th1
Novavax XBB.1.5 Vaccine 2023 -2024 Formulation
for Individuals ≥12 years
•2 vials per carton
•5 doses per vial
•0.5 mL dose
•Ready to use•Stable at 2°C to 8°C
•9-month shelf life*
•Use within 12 hours of
first puncturePresentationTransportation & StorageDosing*
•Single dose for previously vaccinated with any COVID -19
vaccine
•If unvaccinated,2-dose series
3* FDA review ongoing
XBB.1.5 Primary Series
Neutralizing Responses
Non-human primate data demonstrates Novavax
vaccine technology induces broadly neutralizing
antibodies with primary vaccination
4
Neutralizing Responses in Macaques: Primary Vaccination with XBB.1.5
Primary vaccination induces comparable neutralizing responses to newly emerging variants
5N = 10; Assay validated for  human samples for Prototype and XBB.1.5
2 Doses: XBB.1.5 rS
Prototype XBB.1.5 XBB.2.3 XBB.1.16 XBB.1.16.6 EG.5.1 FL.1.5.1 242628210212214216
Pseudovirus
Neutralization
(ID50, GMT)
95% CI
LOD
 Variants Pseudovirus
XBB.1.5 Booster Dose
Neutralizing Responses
Neutralizing responses against XBB subvariants
achieve levels comparable to homologous XBB.1.5
response
6
Neutralizing Responses in Macaques: Primary Vaccination
Bivalent BA.5 Vaccine and Boost with XBB.1.5
Boosting with XBB.1.5 induces robust neutralizing responses against emerging XBB subvariants
7 N = 4 -5
Bivalent Primary and XBB.1.5 Booster Dose
PrototypeXBB.1.5 XBB.2.3XBB.1.16XBB.1.16.6EG.5.1 FL.1.5.1PrototypeXBB.1.5 XBB.2.3XBB.1.16XBB.1.16.6EG.5.1 FL.1.5.12022242628210212214216218
Pseudovirus
Neutralization
(ID50, GMT)
95% CI
LOD  2 weeks Post XBB.1.5 Boost  5 weeks Pre Booster
 6.9x      71x    39x      62x    >150x   >150x  >150x
Cellular Immune Responses
Consistent responses against all variants including
emerging XBB subvariants
8
Th1-Biased CD4+ T Cell Response in Rhesus Macaques
Immunized with Two Doses of XBB.1.5 Vaccine
Consistent responses against all variants including emerging XBB subvariants
9 N = 5
Primary 2 Dose: XBB.1.5
PrototypeXBB.1.5
XBB.1.16.6EG.5.1
PrototypeXBB.1.5
XBB.1.16.6EG.5.1
PrototypeXBB.1.5
XBB.1.16.6EG.5.1
PrototypeXBB.1.5
XBB.1.16.6EG.5.1
PrototypeXBB.1.5
XBB.1.16.6EG.5.1100101102103104105
Th1/Th2
Cytokine+ Cells
(per 106CD4+
T cells)
MeanTh1 Th2
IFN-γ IL-2 TNF-α IL-5 IL-13
Stimulation rS
Public Health Value of Novavax XBB.1.5 Vaccine
•Only protein -based COVID -19 vaccine in US
•Non-clinical data supports use of Novavax XBB.1.5 vaccine
-Induces  robust neutralizing responses against XBB subvariants
-Generates a polyfunctional Th1 -biased CD4+ cellular immune response
against XBB subvariants
•Presentation facilitates ease of use
-Same dose/formulation/vial for all approved indications (0.5mL/dose)
-Ready to use and refrigerator stable (no mixing, dilution or thawing)
10

Summary: Data in Support of Novavax XBB.1.5 Vaccine Dr. Filip Dubovsky , President, Research & Development September 12, 2023 1 Novavax Vaccine Platform: Recombinant Protein  Particle Plus Matrix -M™ Adjuvant    2Recombinant protein particle Native 3-dimensional conformation Truncated S. frugiperda glycans  Particulate structure facilitates antigen  presentation and processing Novavax  2023- 2024 vaccine Matrix -M adjuvant Induces robust neutralizing antibodies Induces polyfunctional CD4+ Th1 …


10 COVID Modjarrad 508

1 Breakthroughs that change patients’ lives Monovalent XBB.1.5 BNT162b2 COVID-19 Vaccine
ACIP Presentation September 12, 2023
CC-2Presentation Outline
Kayvon Modjarrad, M.D., Ph.D.
Executive Director, Viral Vaccines
Vaccine Research and Development, Pfizer Inc. Variant Epidemiology
COVID-19 Updated Vaccine
Approval Pathway
Monovalent XBB.1.5 BNT162b2
Vaccine Activity Against
Contemporary Omicron Sublineages
Clinical Update

CC-3XBB Sublineages Continue to Dominate the Epidemiolo gic
Landscape, Despite the Emergence of New Lineages
Growing Dominance of EG.5.1
Source: 3D Spike Model - Pfizer
Mutation Prediction - jbloomlab.github.io/SARS2-RBD-escape-calc Source: GISAID - gisaid.org , data accessed/analyzed in Pizer, September 08, 20 23
BA.2.86 has high mutational density in Spike
protein but accounts for <1% of cases

CC-4Pathway for COVID-19 Variant-Adapted Vaccine Update s
COVID-19
Vaccine
Development Early-stage development
“at risk” and
surveillance to inform
variant selection Manufacture (pre-clinical
and CMC data), Regulatory
Submissions and Review Distribute Vaccines Strain Selection FDA Authorization/Approval
ACIP Recommendation
• In accordance with FDA guidance for licensure, pre clinical/CMC
data package submission and review help ensure time ly
availability of seasonal variant-matched vaccine, s imilar to the
model for annual influenza vaccine updates.
CC-5Clinical and Preclinical Experience with Variant-mo dified Vaccines –
Supported Bivalent BA.4/5 Vaccine Authorization
Preclinical Data Clinical Data Vaccine Regimen Age Group Modified Vaccine Beta monovalent Omicron BA.1 monovalent Omicron BA.1 bivalent Omicron BA.4/5 bivalent
Ongoing Single Dose 12 to 55 years
>55 years Omicron XBB.1.5 monovalent
18 to 55 years
18 to 55 years
18 to 55 years
>55 years
6 months to 11 years
12 to 55 years
>55 years
Original Vaccine
 Variant Vaccine

CC-6Booster Vaccination Study Design
Female Balb/c mice (10 per group) were experienced with a primary series of monovalent BNT162b2 Origin al vaccine and a 3 rd booster dose of
bivalent BNT162b2 (Original+BA.4/5) vaccine. Mice t hen received a 4 th booster dose of either a bivalent BNT162b2 (Origina l+BA.4/5) or a monovalent
BNT162b2 (XBB.1.5) vaccine.
Data were generated by same pseudovirus neutralizat ion assay and from sera of same mouse study present ed at VRBPAC June 15, 2023 meeting
(https://www.fda.gov/media/169541/download ).
Data on file: Pfizer-BioNTech. September 2023. Blood sample
 Vaccination
0 21 105 134 Day: 160
Monovalent
Original Monovalent
Original Bivalent
Original+BA.4/5 Bivalent
Original+BA.4/5
Monovalent
XBB.1.5

CC-7Monovalent XBB.1.5 BNT162b2 Booster Vaccine Effectiv ely Neutralized
Predominant and Emerging Variants
Data were generated by the same pseudovirus neutral ization assay and from sera of same mouse study tha t generated data that were presented at VRBPAC June 15, 2023 Meeting ( https://www.fda.gov/media/169541/download ).
50% Neutralization Titers are Geometric Mean Titers  of 10 mice per vaccine group. LOD, limit of detect ion; the lowest serum dilution of 1:20.

CC-8Monovalent XBB.1.5 BNT162b2 Booster Vaccine Elicite d Substantially Higher
Neutralizing Response Compared to the Bivalent Vacc ine
Data were generated by same pseudovirus neutralizat ion assay and from sera of same mouse study that ge nerated data that were presented at VRBPAC June 15,  2023 Meeting ( https://www.fda.gov/media/169541/download ).
GMR = Geometric Mean Ratio of the Geometric Mean Ti ter (GMT) of Monovalent XBB.1.5 divided by GMT of W T+BA.4/5 group.  LOD, limit of detection; the lowes t serum dilution of 1:20.
/uni0047/uni004D/uni0052/uni0020/uni0028/uni0072/uni0065/uni006C/uni0061/uni0074/uni0069/uni0076/uni0065/uni0020/uni0074/uni006F/uni0020/uni004F/uni0072/uni0069/uni0067/uni0069/uni006E/uni0061/uni006C/uni0020/uni002B/uni0020/uni0042/uni0041/uni002E/uni0034/uni002F/uni0035/uni0029

CC-9Blood sample
 Vaccination
0 21 49 Day:
Bivalent
(Original/BA.4/5)
Monovalent
XBB.1.5
Bivalent
(Original/BA.4/5)
Monovalent
XBB.1.5 Primary Series Study Design
Female Balb/c mice (10 per group) were administered  2 doses (21 days apart) of either bivalent BNT162b 2 (Original+BA.4/5) or monovalent
BNT162b2 (XBB.1.5) vaccine.
Data were generated by same pseudovirus neutralizat ion assay and from sera of same mouse study present ed at VRBPAC June 15, 2023 meeting
(https://www.fda.gov/media/169541/download ).
Data on file: Pfizer-BioNTech. September 2023.
CC-10These data were generated by same pseudovirus neutr alization assay and from sera of same mouse study t hat generated data that were presented at VRBPAC Jun e 15, 2023 Meeting ( https://www.fda.gov/media/169541/download ).
50% Neutralization Titers are Geometric Mean Titers  of 10 mice per vaccine group.
LOD, limit of detection; the lowest serum dilution of 1:20. Monovalent XBB.1.5 BNT162b2 Primary Series Effectiv ely Neutralized
EG.5.1 and XBB.1.5

CC-11Monovalent XBB.1.5 BNT162b2 Primary Series Elicited  Substantially Higher
Neutralizing Response Compared to the Bivalent Vacc ine
These data were generated by same pseudovirus neutr alization assay and from sera of same mouse study t hat generated data that were presented at VRBPAC Jun e 15, 2023 Meeting ( https://www.fda.gov/media/169541/download ).
GMR = Geometric Mean Ratio of the Geometric Mean Ti ter (GMT) of Monovalent XBB.1.5 and Bivalent XBB.1. 5+BA.4/5 divided by GMT of WT+BA.4/5 group.
LOD, limit of detection; the lowest serum dilution of 1:20.

CC-12Monovalent XBB.1.5 BNT162b2 Clinical Study in Individuals ≥ 12 years
Monovalent XBB.1.5 BNT162b2 30µg
Group 1 (n=200): 12- 55 years
Group 2 (n=200): >55 years
CC-13• The SARS-CoV-2 epidemiologic landscape remains dom inated by XBB
sublineages.
• Monovalent XBB.1.5 BNT162b2 is equally immunogenic  against XBB.1.5,
EG.5.1 and BA.2.86, in a COVID-19 vaccine-experienc ed preclinical study.
• Variant-adapted vaccines improve immune responses against antigenically
matched and closely related strains.
• A preclinical/CMC package for variant-adapted COVI D-19 vaccine fulfilled
licensure criteria. Summary
14 Breakthroughs that change patients’ lives Monovalent XBB.1.5 Pfizer-BioNTech COVID-19 Vaccine
ACIP September 12, 2023

Summary: 1 Breakthroughs that change patients’ lives Monovalent XBB.1.5 BNT162b2 COVID-19 Vaccine  ACIP Presentation September 12, 2023  CC-2Presentation Outline  Kayvon Modjarrad, M.D., Ph.D.  Executive Director, Viral Vaccines  Vaccine Research and Development, Pfizer Inc. Variant Epidemiology  COVID-19 Updated Vaccine  Approval Pathway  Monovalent XBB.1.5 BNT162b2  Vaccine Activity Against  Contemporary Omicron Sublineages  Clinical Update   CC-3XBB Sublineages Continue to Dominate the Epidemiolo…