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Pfizer/BioNTech 

COVID-19 Omicron-Modified 

Bivalent Vaccine

September 01, 2022

Dr Kena Swanson, Ph.D.

Vice President, Viral Vaccines R&D, Pfizer
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Important Disclaimer

The information in these slides and discussed during the 

presentation, including scientific approaches, assumptions 

regarding potential safety and efficacy, clinical trial and 

manufacturing plans and timing estimates, are subject to change 

based on emerging data, regulatory guidance, and manufacturing 

and technical developments, among other risks.
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SARS-CoV-2 Epidemiology Changes Quickly

Omicron BA.5 Now Predominant VOC

GISAID data as of August 30, 2022
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Preclinical Data Have Reliably Predicted Clinical Results for 

Variant-modified Vaccines
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Clinical Study For Monovalent Omicron BA.1-modified Vaccine Candidate

Booster and Primary Series

18-55y Participants

C4591031 Substudy D evaluates safety and immunogenicity in ~1,420 participants

(n=~600)

BNT162b2 or Monovalent Omicron 4th dose in 

BNT162b2-experienced (3 prior doses) individuals

Dose 4 administered 3.9 months (3.3, 6.5) from Dose 3

(n=~205)

Monovalent Omicron

2-dose primary series

or

BNT162b2 30 μg 

BNT162b2

30 μg 

Monovalent Omi 

(BA.1)

30 μg 

Monovalent Omi 

(BA.1)

EUA Guidance

• Omicron neutralization:

• GMR Simple Superiority: the lower bound of the 95% confidence interval for the GMR is >1

• Seroresponse Noninferiority: the lower bound of the 95% confidence interval for the percentage 

difference is greater than -5

• Reference strain neutralization: 

• Descriptive analyses: comparison of geometric mean neutralizing titers for reference strain (USA-WA1/2020)

GMR, geometric mean ratio
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15 17

11

16

34

593

10

100

1,000

10,000

USA-WA1/2020 Delta Omicron BA.1

In Naïve Individuals, Monovalent Omicron BA.1 Vaccine Candidate Elicits 

a Predominantly Omicron-specific Response

30 μg Dose, Evaluable Immunogenicity Population – Sentinel Group FFRNT50 GMTs and 95% CIs

Prevax 1 Month Prevax 1 Month Prevax 1 Month

Participants WITHOUT Evidence of Infection up to 1 Month After Dose 2 

FFRNT, fluorescent focus reduction neutralization test

N=9 for all groups without evidence of infection up to 1 month after dose 2 shown out of total N=30 sentinel cohort
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Preclinical Data Demonstrate Superior Neutralization Breadth with 

Bivalent WT/Omicron BA.1 Vaccine 2-Dose Primary Series Compared to 

Prototype and Omicron BA.1 Monovalent Vaccine Candidate

Vaccines administered at 0.5 mcg dose level at Days 0 and 21 to naïve mice

LOD, Limit of Detection; Reference strain, Wuhan-Hu-1

7,216

196

6,013

2,145

184

3,610

1,648

228

2,725

231

8,266

2,931

158

2,989 1,164

BNT162b2

(WT)

BNT162b2

(Omicron)

BNT162b2 Bivalent

(WT/Omicron)

Reference strain Beta Delta Omicron BA.1 Omicron BA.4/5

LOD

101

102

103

104

105

Fold decrease from BA.1: 1.5 2.8 2.5

1M Post-Dose 2 in Naive Mice

Pseudovirus Neutralization Titer 

(NT50)
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Clinical Study to Evaluate Monovalent and Bivalent

Omicron BA.1-modified Vaccine Candidates in Vaccine-experienced Participants

>55y Participants

BNT162b2

(n=~320 each)

30 or 60 μg 

BNT162b2

or or

30 or 60 μg 

Monovalent BNT162b2 

Omi (BA.1)

(n=~320 each)

30 or 60 μg Bivalent 

BNT162b2 + 

BNT162b2 Omi (BA.1)

(n=~320 each)

Monovalent BNT162b2 Omi (BA.1) 60 μg (N~330), bivalent BNT162b2 + BNT162b2 Omi (BA.1) 

30 μg (N~180) and 60 μg (N~480) also being evaluated in participants 18-55 years of age

C4591031 Substudy E Evaluates Safety & Immunogenicity in ~1920 participants >55 Years

Dose 4 administered a median of 6.3 months (4.7, 12.9) from Dose 3
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Omicron BA.1 GMR Consistent with Superiority Criteria for Bivalent 

Omicron BA.1-modified Vaccine Candidate

>55y Participants

GMT

(95% CI)

1M Post-Dose

Vaccine Group / BNT162b2 30 μg

Assay Vaccine Groups n

GMR

(95% CI)

Met Superiority 

(Y/N)*

SARS-CoV-2 

neutralization 

assay –

Omicron BA.1 

– NT50 (titer)

BNT162b2 30 μg 163 455.8 

(365.9, 567.6)

Bivalent OMI BA.1 30 μg 178 711.0 

(588.3, 859.2)

1.56 

(1.17, 2.08) Y

Participants WITHOUT Evidence of Infection up to 1 Month After the Study Vaccination

GMR Simple/Super superiority criteria: the lower bound of 95% confidence interval for GMR is >1.0/1.5 respectively 

Omicron BA.1 NT50 measured using validated 384-well assay
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Omicron BA.1 Seroresponse Rate Exceeds Non-inferiority 

Criterion for Bivalent Omicron BA.1-modified Vaccine Candidate

>55y Participants

Participants WITHOUT Evidence of Infection up to 1 Month After the Study Vaccination

n (%)

(95% CI)

1M Post-Dose

Seroresponse Difference in %

Vaccine Group – BNT162b2 30 μg

%

(95% CI)

Met Non-inferiority

Assay Vaccine Groups N (Y/N)*

SARS-CoV-2 

neutralization 

assay –

Omicron 

BA.1 –

NT50 (titer)

BNT162b2 30 μg 149 85 (57.0) (48.7, 65.1)

Bivalent OMI BA.1 30 μg 169 121 (71.6) (64.2, 78.3) 14.6 

(4.0, 24.9) Y

Non-inferiority criterion: the lower bound of 95% confidence interval for interval for the percentage difference is >-5

Omicron BA.1 NT50 measured using validated 384-well assay
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74.3 455.8 77.2 711.0

10

100

1000

BNT162b2

(30 μg)

Bivalent OMI BA.1

(30 μg)

NT50

(titer) GMT

163 169 166 174 169 178 162 175

Omicron BA.1 Neutralization Activity Substantially Increased 

with Bivalent Omicron BA.1-modified Vaccine Candidate as 4th Dose Booster

>55y Participants

>55 Year Olds Without Evidence of Prior Infection

Median Time from Dose 3 to Study Vaccination: 6.3 Months (4.7, 12.9)

Prevax 1MPD Prevax 1MPD

Omicron BA.1 NT50 measured using validated 384-well assay

5.8 9.1 GMFR
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Non-inferiority of Reference Strain GMR Demonstrated for Bivalent 

Omicron BA.1 Vaccine Candidate

>55y Participants, Expanded Cohort (Evaluable Immunogenicity Population)

GMT

(95% CI)

1M Post-Dose

Vaccine Group / BNT162b2 30 μg

Assay Vaccine Groups n

GMR

(95% CI)

Met Non-inferiority 

(Y/N)

SARS-CoV-2 

neutralization 

assay –

reference 

strain – NT50 

(titer)

BNT162b2 30 μg 182 5998.1

(5223.6, 6887.4)

Bivalent OMI BA.1 30 μg 186 5933.2

(5188.2, 6785.2)

0.99

(0.82, 1.20) Y

Participants WITHOUT Evidence of Infection up to 1 Month After the Study Vaccination

Non-inferiority criterion: the lower bound of 95% confidence interval for GMR >0.67 (1.5-fold criterion)

Reference strain (USA-WA1/2020) NT50 measured using validated 384-well assay
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Reactogenicity Profile of Bivalent Omicron BA.1 Variant Vaccine 

Candidate Overall Similar to Prototype BNT162b2 Vaccine

C4591031 Substudy Ea(>55y)

BNT162b2

30 μg

Bivalent OMI BA.1

30 μg

Dose 4

(N=298)

Dose 4

(N=301)

Local reaction at injection site

Pain 60.1% 58.1%

Swelling 6.0% 6.6%

Redness 6.4% 7.0%

Systemic events

Fatigue 45.3% 49.2%

Headache 26.5% 33.6%

Muscle pain 19.8% 22.3%

Chills 16.4% 13.0%

Joint pain 9.1% 11.3%

Fever (≥38.0°C) 3.7% 5.0%

Vomiting 1.3% 1.7%

Diarrhea 4.4% 9.0%

a. BNT162b2-experienced participants (>55 years of age) who received BNT162b2 30 μg or BNT162b2 + BNT162b2 

OMI BA.1 30 μg as a booster dose (Dose 4) approximately 5 to 12 months after their last dose (Dose 3).
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425.7 110.9 771.3 226.3

10

100

1,000

10,000

BNT162b2 30 μg

n=17

Bivalent OMI BA.1 30 μg

n=13

BA.1 BA.4/5

LOD

Bivalent Omicron BA.1-modified Variant Vaccine Candidate as 4th Dose 

Elicits Improved Omicron BA.1 Neutralization Response; BA.4/BA.5 Neutralized to Lesser Extent

>55y Participants Sentinel Cohort, 30 and 60 μg Dose

Participants WITHOUT Evidence of Infection up to 1 Month After First Study Vaccination 

BA.4/BA.5 response lower compared to BA.1
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1M Post 3rd Dose Booster Following 2 Doses of BNT162b2

Similar to Clinical Data, Omicron BA.1 Monovalent and Bivalent Booster 

in Mice Increases Omicron Neutralization Response; Continued 

Trend for Reduced BA.4/BA.5 Neutralization Compared to BA.1

53,993 1,358 570 13,648 8,067 1,064 54,422 8,717 1,477

BNT162b2

(WT)

BNT162b2

(Omicron BA.1)

BNT162b2 Bivalent

(WT/Omicron BA.1)

Reference strain Omicron BA.1 Omicron BA.4/5

101

102

103

104

105

106 BA.4/BA.5 response lower compared to BA.1

Pseudovirus Neutralization Titer 

(NT50)

Mice preimmunized with 2 doses of BNT162b2; boosters given 1 month post Dose 2

Vaccines administered at 0.5 mcg dose level. LOD, Limit of Detection; Reference strain, Wuhan-Hu-1

LOD
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Omicron BA.4/BA.5 Monovalent and Bivalent Boosters in Mice 

Substantially Increase Omicron Neutralization Responses 

to all Omicron Variants Including BA.4/5

Mice preimmunized with 2 doses of BNT162b2; boosters given at day 104 post Dose 2

Vaccines administered at 1 mcg dose level; Wild type, Wuhan-Hu-1; LOD, Limit of Detection

Compared to BNT162b2 Neutralizing BA.4/5 titers increase 

by ~6.2 fold [mono BA.4/5] or ~2.6 fold (bivalent BA.4/5) Day 7 PD3
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7d Post 3rd Dose Booster Following 2 Doses of BNT162b2

Confirmatory Study: Omicron BA.4/BA.5 Monovalent and Bivalent Boosters in Mice 

Substantially Increase Omicron Neutralization Responses 

to all Omicron Variants Including BA.4/5

BNT162b2 OMI4/5 BNT162b2 + 10

1

10

2

10

3

10

4

10

5

10

6

50% pVNT Titer

BNT162b2 OMI4/5

8.62 1.24 Fold Increase

from BA.1

Omicron BA.2

Wuhan Omicron BA.1 Omicron BA.2.12.1 Omicron BA.4/BA.5 LOD

7D Post 3

rd Dose Booster

following BNT162b2 2-Dose Primary Series

Mice preimmunized with 2 doses of BNT162b2; boosters given 1 month post Dose 2

Vaccines administered at 0.5 mcg dose level; LOD, Limit of Detection; Reference strain, Wuhan-Hu-1

Reference strain

Omicron BA.1

Omicron BA.2

Omicron BA.2.12.1

Omicron BA.4/BA.5

Pseudovirus Neutralization Titer 

(NT50)
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Omicron BA.4/BA.5-modified Variant Vaccine Summary

• Reactogenicity profile of variant vaccines (Beta, Omicron BA.1) overall similar to 

prototype BNT162b2 vaccine

• Neutralizing responses for Omicron-containing vaccines 

are consistent with regulatory criteria:

– Simple superiority for Omicron BA.1 GMR and non-inferiority for seroresponse (monovalent 

and bivalent vaccines)

– Non-inferiority for reference strain GMR

• Preclinical immunogenicity data reliably predict observations in humans

• Omicron BA.4/5-modified variant vaccine booster elicits improved neutralizing response 

across Omicron sublineages
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THANK YOU!