CompletedNCT05004181Updated Nov 22, 2024Results posted

Safety and Immunogenicity of RNA-based Vaccines Against SARS-CoV-2 Variants in Healthy Participants

A Phase 2 interventional study of BNT162b2 and Multivalent BNT162b2 (B.1.1.7 + B.1.617.2) in SARS-CoV-2 Infection, COVID-19 and SARS-CoV-2 Acute Respiratory Disease, sponsored by BioNTech SE. Completed at 35 sites in 4 countries. Open to participants aged 18 Years to 85 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-11-22.

Sponsored by BioNTech SE · Phase 2, Interventional, and Prevention

Phase: Phase 2
Study type: Interventional
Enrollment: 1,380
Allocation: Non-randomized
Ages: 18 Years to 85 Years
Sex: All

Study summary

This trial consisted of three parts, Part A, Part B, and Part C, and evaluated the safety and immunogenicity of a third (booster) injection of the multivalent vaccine BNT162b2 (B.1.1.7 + B.1.617.2), and the safety and immunogenicity of a third booster injection of the monovalent vaccine BNT162b2 (B.1.617.2) or BNT162b2 (B.1.1.7), in participants who had received two doses of the parent vaccine BNT162b2 at 30 µg, at least 6 months after the second dose of BNT162b2. It also evaluated the safety and immunogenicity of a three-dose regimen of BNT162b2 (B.1.1.7 + B.1.617.2) in participants who had not received prior Coronavirus Disease 2019 (COVID-19) vaccination. In addition, the safety and immunogenicity of BNT162b2 (B.1.1.529.1) or BNT162b2 given as a third or fourth vaccine dose to RNA COVID-19 vaccine-experienced participants with history of SARS-CoV-2 Omicron variant infection was evaluated and contrasted with the natural immune response reached after infection with the SARS-CoV-2 Omicron variant in RNA COVID-19 vaccine-experienced participants.

Read the detailed description

Trial participants in Part A were assigned to one of 6 cohorts (Cohort 1-6). Trial participants in Part B were assigned to one of 3 cohorts (Cohort 1, 4, and 6). Trial participants in Part C were randomized in a 2:2:1 ratio into 3 cohorts (Cohort 7-9).

Conditions studied

SARS-CoV-2 Infection
COVID-19
SARS-CoV-2 Acute Respiratory Disease
SARS (Disease)

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In context

COVID-19

7,640 studies on the registry are indexed under COVID-19; 488 are open to participants now.

This study's enrollment of 1,380 is above the median of 100 across 4,099 interventional studies indexed under COVID-19.

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Lead sponsor

BioNTech SE is the lead sponsor of 74 studies on the registry; 23 are open to participants now.

Of its 32 completed or terminated interventional studies of FDA-regulated products, 26 (81%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 85 Years
Sexes eligible: All
Accepts healthy volunteers: Yes

Inclusion criteria

Had given informed consent by signing the informed consent form (ICF) before initiation of any trial-specific procedures.
Volunteers who at the time of consent were:
Part A: 18 to 55 years old.
Part B and Part C: 18 to 85 years old (\~60% should be 18 to 55 years old and \~40% 56 to 85 years old).
For Cohorts 1 to 5: In Part A, who had received BNT162b2 vaccine (30 µg, two-dose regimen) in either a clinical trial or as part of the governmental vaccination programs at least 6 months before Visit 0. Participants who were currently enrolled in the Phase III BNT162-02 / C4591001 (NCT04368728) trial, had already been unblinded, and had previously received two doses of BNT162b2 at least 6 months earlier could be included (for Cohorts 1 and 4 in Part B, prior enrollment and dosing in the C4591001 trial was mandatory). At enrollment into Part B of this trial, their participation in the C4591001 trial was terminated. Participants should have not had experienced COVID-19 based on medical history.
For Cohort 6: Were COVID-19 vaccine-naïve and had not experienced COVID-19 based on their medical history.
Were willing and able to comply with all scheduled visits, vaccination plan, laboratory tests, lifestyle considerations, and other trial procedures.
Were overall healthy at Visit 0 in the clinical judgment of the investigator based on the medical history, clinical assessment (including physical examination, vital signs, blood and urine clinical laboratory tests, 12-lead electrocardiogram (ECG), and oral swab for Nucleic Acid Amplification-based Test (NAAT)-based Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) testing).
Note: Healthy volunteers with pre-existing stable disease, defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 12 weeks before Visit 0, could be included.
Note: Volunteers who had hepatitis C (HCV) infection, but had completed curative treatment based on the medical history could be included. Volunteers who had or have hepatitis B (HBV) or human immunodeficiency virus (HIV) based on the medical history could not be included.
Agreed not to enroll in another trial of an Investigational Medicinal Product (IMP), starting after Visit 0 and continuously until the last planned visit in this trial.
Women of childbearing potential (WOCBP) had to test negative in a urine beta-human chorionic gonadotropin (β-HCG) test at Visits 0 and 1.
WOCBP had to agree to practice a highly effective form of contraception starting at Visit 0 and continuously until 28 days after their last IMP administration in this trial.
WOCBP had to confirm that they practiced an acceptable form of contraception for the 14 days prior to Visit 0.
WOCBP had to agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction starting after Visit 0 and continuously until 28 days after their last IMP injection in this trial.
Men who are sexually active with a WOCBP and had not had a vasectomy had to agree to use a highly effective form of contraception with their female partner of childbearing potential starting after Visit 0 and continuously until 28 days after their last IMP injection in this trial.
Men had to be willing to refrain from sperm donation, starting after Visit 0 and continuously until 28 days after their last vaccination.
For Part C, Cohorts 7, 8, and 9: Had received two or three documented doses of any authorized COVID-19 RNA-based vaccine (e.g., BNT162b2 [Comirnaty] or the Moderna vaccine [Spikevax]) prior to being diagnosed with SARS-CoV-2 infection from January 2022 onwards (and limited to a period when there was a high prevalence of SARS-CoV-2 Omicron infections).
Note: The interval between the last COVID-19 RNA-based vaccine administered and randomization should have been >4 months. The latest prior diagnosed SARS-CoV-2 infection should have been at least 2 months before randomization. The latest SARS-CoV-2 infection should have been documented with a result from a NAAT (as a preferable option). In case no historic NAAT result was available proving prior SARS-CoV-2 infection, the local positive result of SARS-CoV-2 N-binding antibodies done at screening was sufficient.

Exclusion criteria

Exclusion Criteria:

Any existing condition which could have affected vaccine injection and/or assessment of local reactions assessment, e.g., tattoos, severe scars, etc.
Any bleeding diathesis or condition associated with prolonged bleeding that could have, in the opinion of the investigator, contraindicated intramuscular injection.
Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that, in the investigator's judgment, made the participant inappropriate for the trial.
Any current febrile illness (body temperature ≥38.0°C/≥100.4°F) or other acute illness within 48 h prior to Day 1/IMP injection in this trial.
Any current or history of cardiovascular diseases, e.g., myocarditis, pericarditis, myocardial infarction, congestive heart failure, cardiomyopathy or clinically significant arrhythmias, unless such disease was not considered relevant for participation in this trial in the investigator's judgment.
History of COVID-19 and/or clinical (based on COVID-19 symptoms/signs alone, if a SARS CoV 2 NAAT result was not available) or microbiological (based on COVID-19 symptoms/signs and a positive SARS CoV 2 NAAT result) evidence of prior infection with SARS CoV 2 at screening (Visit 0).
Note: not applicable for Part C.
History of Guillain-Barré syndrome.
Known or suspected immunodeficiency.
History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (e.g., anaphylaxis) to any component of the trial IMPs.
History or known allergy, hypersensitivity, or intolerance to the trial IMP including any excipients of the IMPs in this trial.
Had received any SARS CoV 2 vaccination other than BNT162b2 (30 µg BNT162b2 given as a course of two doses approximately 21 days apart).
Note: not applicable for Part C.
Had received a live or live attenuated vaccine within 28 days prior to Day 1/IMP injection.
Had received any other vaccines within 14 days before or after any IMP injection, e.g., influenza, tetanus, pneumococcal, hepatitis A or B. When possible standard of care vaccinations should been planned with the trial IMP administrations in mind.
Individuals who received treatment with radiotherapy or immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids (if systemic corticosteroids were administered for ≥14 days at a dose of ≥20 mg/day of prednisone or equivalent), e.g., for cancer or an autoimmune disease, or planned receipt throughout this trial. Inhaled/nebulized, intra-articular, intrabursal, or topical (skin or eyes) corticosteroids were permitted.
Receipt of blood/plasma products or immunoglobulin, from 60 days before IMP administration or planned receipt throughout this trial.
Participation in other trials involving IMP within 28 days or 5 half-lives (whichever was longer) prior to Visit 1 and/or during trial participation, besides participation in trials with BNT162b2.
Were pregnant or breastfeeding or are planning pregnancy within 28 days after last IMP treatment.
Were vulnerable individuals as per International Conference on Harmonisation (ICH) E6 definition, i.e., are individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate.
For Part C, Cohorts 7, 8, and 9: Vaccination with other non-RNA or unauthorized COVID-19 vaccines.
For Part C, Cohorts 7, 8, and 9: Vaccination with any COVID-19 vaccine after SARS-CoV-2 infection from January 2022 onwards (and limited to a period when there was a high prevalence of SARS-CoV-2 Omicron infections).

Study design

Phase: Phase 2
Primary purpose: Prevention
Allocation: Non-randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 1,380 participants (actual)

Study arms

Experimental
Part A - Cohort 1: 18 to 55 years of age
Participants received 1 dose of BNT162b2 (B.1.1.7 + B.1.617.2) of 30 µg.
Biological: Multivalent BNT162b2 (B.1.1.7 + B.1.617.2)
Experimental
Part A - Cohort 2: 18 to 55 years of age
Participants received 2 doses of BNT162b2 (B.1.1.7 + B.1.617.2) of 30 µg.
Biological: Multivalent BNT162b2 (B.1.1.7 + B.1.617.2)
Experimental
Part A - Cohort 3: 18 to 55 years of age
Participants received1 dose of BNT162b2 (B.1.1.7) of 30 µg.
Biological: Monovalent BNT162b2 (B.1.1.7)
Experimental
Part A - Cohort 4: 18 to 55 years of age
Participants received 1 dose of BNT162b2 (B.1.617.2) of 30 µg.
Biological: Monovalent BNT162b2 (B.1.617.2)
Experimental
Part A - Cohort 5: 18 to 55 years of age
Participants received 1 dose of BNT162b2 of 30 µg.
Biological: BNT162b2
Experimental
Part A - Cohort 6: 18 to 55 years of age
Participants received 3 doses of BNT162b2 (B.1.1.7 + B.1.617.2) of 30 µg.
Biological: Multivalent BNT162b2 (B.1.1.7 + B.1.617.2)
Experimental
Part B - Cohort 1: 18 to 85 years of age
Participants received 1 dose of BNT162b2 (B.1.1.7 + B.1.617.2) of 30 µg.
Biological: Multivalent BNT162b2 (B.1.1.7 + B.1.617.2)
Experimental
Part B - Cohort 4: 18 to 85 years of age
Participants received 1 dose of BNT162b2 (B.1.617.2) of 30 µg.
Biological: Monovalent BNT162b2 (B.1.617.2)
Experimental
Part B - Cohort 6: 18 to 85 years of age
Participants received 3 doses of BNT162b2 (B.1.1.7 + B.1.617.2) of 30 µg.
Biological: Multivalent BNT162b2 (B.1.1.7 + B.1.617.2)
Experimental
Part C - Cohort 7: 18 to 85 years of age
Participants received 1 dose of BNT162b2 (B.1.1.529.1) of 30 µg.
Biological: Monovalent BNT162b2 (B.1.1.529.1)
Experimental
Part C - Cohort 8: 18 to 85 years of age
Participants received 1 dose of BNT162b2 of 30 µg.
Biological: BNT162b2
Other
Part C - Cohort 9: 18 to 85 years of age
Participants received no vaccination within 3 months after Visit 1.
Other: Observational

Interventions

BiologicalBNT162b2
Intramuscular (IM)
BiologicalMultivalent BNT162b2 (B.1.1.7 + B.1.617.2)
Intramuscular (IM)
BiologicalMonovalent BNT162b2 (B.1.1.7)
Intramuscular (IM)
BiologicalMonovalent BNT162b2 (B.1.617.2)
Intramuscular (IM)
BiologicalMonovalent BNT162b2 (B.1.1.529.1)
Intramuscular (IM)
OtherObservational
No vaccination within 3 months after Visit 1.

What researchers measure

Primary outcomes

All Parts - Percentage of Participants Reporting Local Reactions at the Injection Site (Pain, Tenderness, Erythema/Redness, Induration/Swelling)
Local reactions of any grade are reported. Local reactions were graded using criteria based on the US FDA Guidance for Industry "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials"; the guidance uses the Grades 1 (mild), 2 (moderate), 3 (severe), and 4 (potentially life-threatening). The reporting of systemic reactions was based on the participant's assessments collected in the electronic diary (e-diary) or mapped from the adverse event case report form from Day 1 to Day 7 after each IMP dose. For Erythema/redness and Induration/swelling, the reported size had to be at least 2.5 cm to be deemed as a local reaction. Local reactions with a size less than 2.5 cm are not included in the analysis. Subjects in Cohort 9 did not receive a vaccination and are not included in this analysis.
Time frame: from Day 1 to Day 7 after each IMP dose
All Parts - Percentage of Participants Reporting Systemic Events (Fever, Fatigue, Headache, Chills, Vomiting, Nausea, Diarrhea, New or Worsened Muscle Pain, and New or Worsened Joint Pain)
Systemic reactions of any grade are reported. Systemic reactions were graded using criteria based on the guidance given in the US FDA Guidance for Industry "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials"; the guidance uses the Grades 1 (mild), 2 (moderate), 3 (severe), and 4 (potentially life-threatening). The reporting of systemic reactions was based on the participant's assessments collected in the e-diary or mapped from the adverse event case report form from Day 1 to Day 7 after each IMP dose. For Fever, the reported oral temperature had to be ≥38.0°C to be deemed as a systemic event. Oral temperature less than 38.0°C are not included in the analysis. Subjects in Cohort 9 did not receive a vaccination and are not included in this analysis.
Time frame: from Day 1 to Day 7 after each IMP dose
All Parts - Percentage of Participants Reporting Adverse Events (AEs)
An AE is defined as TEAE if the event onset date and time is after the first IMP dose (if the event was absent before the first administration of the IMP) or worsened after the first IMP dose (if the event was present before the first administration of the IMP). In the event of an incomplete onset date, the event is considered as treatment-emergent unless the partial onset date information or complete or partial end date confirms the onset date or the event end prior to the first dose of IMP. Percentages for dose 1, dose 2, dose 3 and overall summaries are based upon the number of participants who received the respective IMP dose.
Time frame: Dose 1 up to 1 month after each dose (all parts)
All Parts - Percentage of Participants Reporting Serious Adverse Events (SAEs)
An SAE was any untoward medical occurrence that, at any dose: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent disability/ incapacity; was a congenital anomaly/birth defect and/or was another important medical event. SAEs from dose 1 up to 6 months post last IMP dose are presented. MedDRA (version 26.1) coding dictionary applied. An SAE is defined as TESAE if the event onset date and time is after the first IMP dose (if the event was absent before the first administration of the IMP) or worsened after the first IMP dose (if the event was present before the first administration of the IMP). In the event of an incomplete onset date, the event is considered as treatment-emergent unless the partial onset date information or complete or partial end date confirms the onset date or the event end prior to the first dose of IMP.
Time frame: Dose 1 up to 6 months after the last dose
Part B - GMR of B.1.1.7 NT 1 Month After 1 Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 (NCT04368728) Trial
GMRs and 2-sided 95% CIs were calculated by exponentiating the difference of least square means and corresponding CIs based on the analysis of logarithmically transformed neutralizing titers using a linear regression model with terms of age, sex, and vaccine group. The overall number of participants analyzed represents the number of participants with valid and determinate assay results for B.1.1.7 and reference strain respectively at the given dose/sampling time point within the specified window. GMR data are presented below as per the primary endpoint defined in the protocol. GMTs for the individual arms (from which GMR was derived) were secondary endpoints and are presented in outcome measure 22. GMR = Geometric mean ratio; NT = neutralizing titers
Time frame: 1 month after booster dose in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial
Part B - GMR of B.1.617.2 NT 1 Month After 1 Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 (NCT04368728) Trial
GMRs and 2-sided 95% CIs were calculated by exponentiating the difference of least square means and corresponding CIs based on the analysis of logarithmically transformed neutralizing titers using a linear regression model with terms of age, sex, and group. The overall number of participants analyzed represents the number of participants with valid and determinate assay results for B.1.617.2 and reference strain respectively at the given dose/sampling time point within the specified window. GMR data are presented below as per the primary endpoint defined in the protocol. GMTs for the individual arms (from which GMR was derived) were secondary endpoints and are presented in outcome measure 22. GMR = Geometric mean ratio; NT = neutralizing titers
Time frame: 1 month after booster dose in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial
Part B - GMR of B.1.617.2 NT 1 Month After 1 Dose of BNT162b2 (B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 (NCT04368728) Trial
GMRs and 2-sided 95% CIs were calculated by exponentiating the difference of least square means and corresponding CIs based on the analysis of logarithmically transformed neutralizing titers using a linear regression model with terms of age, sex, and group. The overall number of participants analyzed represents the number of participants with valid and determinate assay results for B.1.617.2 and reference strain respectively at the given dose/sampling time point within the specified window. GMR data are presented below as per the primary endpoint defined in the protocol. GMTs for the individual arms (from which GMR was derived) were secondary endpoints and are presented in outcome measure 24.
Time frame: 1 month after booster dose in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial
Part B - Difference in Seroresponse (SR) to B.1.1.7 NT 1 Month After 1 Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From C4591001 (NCT04368728)
Seroresponse was defined as a ≥4-fold rise in neutralizing titer from baseline. For subjects with a baseline titer less than the lower limit of quantitation (\<LLOQ), seroresponse was defined as a post-vaccination titer of ≥4× LLOQ. Adjusted difference was estimated using minimum risk weights and stratified by sex and age group (18 to 55 years, 56 to 85 years), expressed as a percentage. Associated 2-sided 95% CI based on the Newcombe method with minimum risk weights for the difference in proportions. Difference in seroresponse data are presented below as per the primary endpoint defined in the protocol. Seroresponses for the individual arms (from which the difference was derived) were secondary endpoints and are presented in outcome measure 23.
Time frame: 1 month after booster dose in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial
Part B - Difference in SR to B.1.617.2 NT 1 Month After 1 Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From C4591001 (NCT04368728)
Seroresponse was defined as a ≥4-fold rise in neutralizing titer from baseline. For subjects with a baseline titer less than the lower limit of quantitation (\<LLOQ), seroresponse was defined as a post-vaccination titer of ≥4× LLOQ. Adjusted difference was estimated using minimum risk weights and stratified by sex and age group (18 to 55 years, 56 to 85 years), expressed as a percentage. Associated 2-sided 95% CI based on the Newcombe method with minimum risk weights for the difference in proportions. Difference in seroresponse data are presented below as per the primary endpoint defined in the protocol. Seroresponses for the individual arms (from which the difference was derived) were secondary endpoints and are presented in outcome measure 23.
Time frame: 1 month after booster dose in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial
Part B - Difference in SR to B.1.617.2 NT 1 Month After 1 Dose of BNT162b2 (B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From C4591001 (NCT04368728)
Seroresponse was defined as a ≥4-fold rise in neutralizing titer from baseline. For subjects with a baseline titer less than the lower limit of quantitation (\<LLOQ), seroresponse was defined as a post-vaccination titer of ≥4× LLOQ. Adjusted difference was estimated using minimum risk weights and stratified by sex and age group (18 to 55 years, 56 to 85 years), expressed as a percentage. Associated 2-sided 95% CI based on the Newcombe method with minimum risk weights for the difference in proportions. Difference in seroresponse data are presented below as per the primary endpoint defined in the protocol. Seroresponses for the individual arms (from which the difference was derived) were secondary endpoints and are presented in outcome measure 25.
Time frame: 1 month after booster dose in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial
Part B - GMR of B.1.1.7 NT 1 Month After 2 Doses of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 Vaccine-naïve Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the C4591001 (NCT04368728) Trial
Cohort B6 aimed to generate data to support a 2-dose primary regimen of alpha-delta multivalent BNT162b2 vaccine in SARS-CoV-2 naïve, unvaccinated individuals. The population recruited in Cohort B6, while complying with the inclusion criterium of no known history SARS-CoV-2 infection, were retrospectively seropositive for SARS-CoV-2 by planned N-binding antibody assessment of baseline samples. While the cohort was COVID-19 vaccine-naïve, it was not SARS-CoV-2-naïve as needed to match the control group (C4591001/NCT04368728). Procedurally, submission of a protocol amendment was not possible. However, the Statistical Analysis Plan was amended to describe that the non-inferiority analysis could not be performed according to the protocol. Control participants were not selected as planned; therefore, data were not available to calculate the GMR. Available GMT data for the 17 Cohort B6 participants without evidence of infection were analyzed and are presented in Outcome Measure 28.
Time frame: 1 month
Part B - GMR of B.1.617.2 NT 1 Month After 2 Doses of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 Vaccine-naïve Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the C4591001 (NCT04368728) Trial
Cohort B6 aimed to generate data to support a 2-dose primary regimen of alpha-delta multivalent BNT162b2 vaccine in SARS-CoV-2 naïve, unvaccinated individuals. The population recruited in Cohort B6, while complying with the inclusion criterium of no known history SARS-CoV-2 infection, were retrospectively seropositive for SARS-CoV-2 by planned N-binding antibody assessment of baseline samples. While the cohort was COVID-19 vaccine-naïve, it was not SARS-CoV-2-naïve as needed to match the control group (C4591001/NCT04368728). Procedurally, submission of a protocol amendment was not possible. However, the Statistical Analysis Plan was amended to describe that the non-inferiority analysis could not be performed according to the protocol. Control participants were not selected as planned; therefore, data were not available to calculate the GMR. Available GMT data for the 17 Part B Cohort 6 participants without evidence of infection were analyzed and are presented in Outcome Measure 28.
Time frame: 1 month
Part B - The Difference in SR to B.1.1.7 NT 1 Month After 2 Doses of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 Vaccine-naïve Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the C4591001 (NCT04368728) Trial
Cohort B6 aimed to generate data to support a 2-dose primary regimen of alpha-delta multivalent BNT162b2 vaccine in SARS-CoV-2 naïve, unvaccinated individuals. The population recruited in Cohort B6, while complying with the inclusion criterium of no known history SARS-CoV-2 infection, were retrospectively seropositive for SARS-CoV-2 by planned N-binding antibody assessment of baseline samples. While the cohort was COVID-19 vaccine-naïve, it was not SARS-CoV-2-naïve as needed to match the control group (C4591001/NCT04368728). Procedurally, submission of a protocol amendment was not possible. However, the Statistical Analysis Plan was amended to describe that non-inferiority analysis could not be performed according to the protocol. Control participants were not selected as planned; therefore, data were not available to calculate difference in SR. Available SR data for the 17 Part B Cohort 6 participants without evidence of infection were analyzed and presented in Outcome Measure 31.
Time frame: 1 month
Part B - The Difference in SR to B.1.617.2 NT 1 Month After 2 Doses of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 Vaccine-naïve Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the C4591001 (NCT04368728) Trial
Cohort B6 aimed to generate data to support a 2-dose primary regimen of alpha-delta multivalent BNT162b2 vaccine in SARS-CoV-2 naïve, unvaccinated individuals. The population recruited in Cohort B6, while complying with the inclusion criterium of no known history SARS-CoV-2 infection, were retrospectively seropositive for SARS-CoV-2 by planned N-binding antibody assessment of baseline samples. While the cohort was COVID-19 vaccine-naïve, it was not SARS-CoV-2-naïve as needed to match the control group (C4591001/NCT04368728). Procedurally, submission of a protocol amendment was not possible. However, the Statistical Analysis Plan was amended to describe that the non-inferiority analysis could not be performed according to the protocol. Control participants were not selected as planned; therefore data were not available to calculate difference in SR. Available SR data for the 17 Part B Cohort 6 participants without evidence of infection were analyzed and presented in Outcome Measure 31.
Time frame: 1 month
Part B - GMR of Reference Strain NT After One Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in Participants With Evidence of Prior Infection to the Reference Strain NT After 2 Doses of BNT162b2 in Participants Without Evidence of Infection
GMR of reference strain NT 3 weeks (3W) after one dose (PD1) of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 vaccine-naïve participants with evidence of prior infection to the reference strain NT 1 month after two doses of BNT162b2 in participants without evidence of infection (COVID-19 Vaccine-naïve Participants) from the Phase III trial C4591001 (NCT04368728). GMTs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and corresponding CIs (based on the Student t distribution). Assay results below LLOQ were set to 0.5 × LLOQ. GMTs of NTs are presented in the descriptive data section of this outcome measure. GMRs and 2-sided 95% CIs were calculated by exponentiating the difference of LS means and corresponding CIs based on the analysis of logarithmically transformed neutralizing titers using a linear regression model with terms of age, sex, and group. GMR data are presented in the statistical analysis section.
Time frame: 3 weeks post Dose 1 in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial
Part B - The Difference in SRs to the Reference Strain NT in Subjects With Evidence of Prior Infection and to the Reference Strain NT in Participants Without Evidence of Infection (COVID-19 Vaccine-naïve Participants)
The difference in SRs to the reference strain NT 3 weeks after one dose of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 vaccine-naïve participants with evidence of prior infection to the reference strain NT 1 month after two doses of BNT162b2 in participants without evidence of infection from the Phase III trial C4591001 (NCT04368728). SR was defined as achieving a ≥4-fold rise from baseline. If the baseline measurement was below the LLOQ, a post-vaccination assay result ≥4 × LLOQ was considered a SR. SR to the reference strain NTs are presented in the descriptive data section of this outcome measure. Adjusted difference in proportions was estimated using minimum risk weights and stratified by sex and age group (18 to 55 years, 56 to 85 years), expressed as a percentage. 2-Sided CI was based on the Newcombe method with minimum risk weights for the difference in proportions. Difference in SR data are presented in the statistical analysis section.
Time frame: 3 weeks post Dose 1 in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial
Part C - GMR of B.1.1.529.1 NT 1 Month After One Dose of BNT162b2 (B.1.1.529.1) in RNA-based COVID-19 Vaccine-experienced Participants With History of SARS-CoV-2 Infection to Those at 1 Month After One Dose of BNT162b2 for Cohorts 7 and 8.
GMRs and 2-sided 95% CIs were calculated by exponentiating the difference of least square means and corresponding CIs based on the analysis of logarithmically transformed neutralizing titers using a linear regression model with terms of age and number of prior doses. The overall number of participants analyzed represents the number of participants with valid and determinate assay results for B.1.1.529.1 at the given dose/sampling time point within the specified window. GMR data are presented below as per the primary endpoint defined in the protocol. GMTs for the individual arms (from which the difference was derived) were secondary endpoints and are presented in outcome measure 32.
Time frame: 1 month after 1 dose of BNT162b2 or BNT162b2 (B.1.1.529.1)
Part C - The Difference in SR of B.1.1.529.1 NT 1 Month After One Dose of BNT162b2 (B.1.1.529.1) in RNA-based COVID-19 Vaccine-experienced Participants With History of SARS-CoV-2 Infection to Those at 1 Month After One Dose of BNT162b2 for Cohorts 7 & 8.
SR was defined as a ≥4-fold rise in neutralizing titer from baseline. For participants with a baseline titer less than the lower limit of quantitation (\<LLOQ), SR was defined as a post-vaccination titer of ≥4× LLOQ. SR to the reference strain NTs are presented in the descriptive data section of this outcome measure. Adjusted difference was estimated using minimum risk weights and stratified by sex and age group (18 to 55 years, 56 to 85 years), expressed as a percentage. Associated 2-sided 95% CI were based on the Newcombe method with minimum risk weights for the difference in proportions. Difference in SR data are presented in the statistical analysis section.
Time frame: 1 month after 1 dose of BNT162b2 or BNT162b2 (B.1.1.529.1)

Secondary outcomes

Part A - Geometric Mean Titer (GMT) at Each Timepoint
For BNT162b2-experienced participants (defined as participants who have previously received two injections of 30 μg BNT162b2). Reference and variant(s) of concern (VOC) specific NT. GMTs and 2-sided 95% CIs are calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ are set to 0.5 × LLOQ and above the ULOQ are set to ULOQ. Cohorts 1, 3, 4 and 5 received only 1 dose of IMP. Cohort 2 received dose 2 on Day 56 and did not receive dose 3. Cohort 6 received dose 2 on Day 21 and received dose 3 approximately 6 months after dose 2.
Time frame: Day 1 up to Day 421
Part A - Geometric Mean Fold Rises (GMFR) From Before Vaccination to Each Subsequent Time Point After Vaccination
For BNT162b2-experienced participants (defined as participants who have previously received two injections of 30 μg BNT162b2). Reference and VOC specific NT. GMFR is calculated as the mean of the difference of logarithmically transformed neutralization titers or antibody levels (later result minus earlier result) and exponentiating the mean. The associated 2-sided 95% CIs are obtained by constructing CIs using Student's t-distribution for the mean difference on the natural log scale and exponentiating the confidence limits. Assay results below the LLOQ are set to 0.5 × LLOQ and above the ULOQ are set to ULOQ. Cohorts 1, 3, 4 and 5 received only 1 dose of IMP. Cohort 2 received dose 2 on Day 56 and did not receive dose 3. Cohort 6 received dose 2 on Day 21 and received dose 3 approximately 6 months after dose 2.
Time frame: Day 1 to Day 421
Part A - Percentage of Participants Achieving SR in Terms of NT at Each Post Vaccination Time Point
For BNT162b2-experienced participants (defined as participants who have previously received two injections of 30 μg BNT162b2). Reference and VOC specific NT. SR is defined as a ≥4-fold rise in neutralizing titer from baseline (pre IMP dose 1). For subjects with a baseline titer less than the LLOQ, SR is defined as a post-vaccination titer of ≥4 × LLOQ. Pre IMP dose 2 is also 2 months post dose 1 for Cohort 2 and 3 weeks post dose 1 for Cohort 6. Cohorts 1, 3, 4 and 5 received only 1 dose of IMP. Cohort 2 received dose 2 on Day 56 and did not receive dose 3. Cohort 6 received dose 2 on Day 21 and received dose 3 approximately 6 months after dose 2.
Time frame: Day 1 to Day 421
Part B - GMT of VOCs and Reference Strains in Part B Cohort 1 and Control
GMTs of VOCs (B.1.1.7 and B.1.617.2) and reference strain 1 month after 1 dose of BNT162 (B.1.1.7+B.1.167.2) in participants from Part B Cohort 1 of the BNT162-17 trial (BNT162b2-experienced participants), and reference strain 1 month after 2 doses of BNT162b2 in selected participants from the Phase III C4591001 (NCT04368728) trial. GMTs and 2-sided 95% CIs are calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ are set to 0.5 × LLOQ and above the ULOQ are set to ULOQ.
Time frame: 1 month after booster dose in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial
Part B - SR of of VOCs and Reference Strains in Part B Cohort 1 and Control
Percentage of participants achieving SR at 1 month after 1 dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced participants (Cohort 1) and 1 month after 2 doses of BNT162b2 primary series (participants from C4591001 \[NCT04368728\]). SR is defined as a ≥4-fold rise in neutralizing titer from baseline (pre IMP dose 1). For participants with a baseline titer less than the LLOQ, SR is defined as a post-vaccination titer of ≥4 × LLOQ.
Time frame: 1 month after Dose 1 in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial
Part B - GMT of VOCs and Reference Strains in Part B Cohort 4 and Control
GMTs of VOCs (B.1.617.2) and reference strain 1 month after 1 dose of BNT162 (B.1.167.2) in participants from Part B Cohort 4 of the BNT162-17 trial (BNT162b2-experienced participants), and 1 month after 2 doses of BNT162b2 in selected participants from the Phase III C4591001 (NCT04368728) trial. GMTs and 2-sided 95% CIs are calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ are set to 0.5 × LLOQ and above the ULOQ are set to ULOQ.
Time frame: 1 month after booster dose in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial
Part B - SR of of VOCs and Reference Strains in Part B Cohort 4 and Control
Percentage of participants achieving SR at 1 month after 1 dose of BNT162b2 (B.1.617.2) in BNT162b2-experienced subjects (Part B - Cohort 4) and 1 month after 2 doses of BNT162b2 primary series (participants from C4591001 \[NCT04368728\]). SR is defined as a ≥4-fold rise in neutralizing titer from baseline (pre IMP dose 1). For participants with a baseline titer less than the LLOQ, SR is defined as a post-vaccination titer of ≥4 × LLOQ.
Time frame: 1 month after Dose 1 in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial
Part B - GMT of VOCs and Reference Strain in Part B Cohort 6 1 Month After Dose 2 and 1 Month After Dose 3
GMTs of VOCs and reference strain NT 1 month after dose 2 and dose 3 of BNT162b2 (B.1.1.7 + B.1.617.2) (Part B - Cohort 6). GMTs and 2-sided 95% CIs are calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ are set to 0.5 × LLOQ and above the ULOQ are set to ULOQ.
Time frame: 1 month after Dose 2 and 1 month after Dose 3
Part B - Cohort 6 - Percentages With SRs to VOCs (B.1.1.7, B.1.617.2) and Reference Strain
Percentage of participants achieving SR to VOCs (B.1.1.7, B.1.617.2) and reference strain at 1 month after dose 2 and dose 3 of BNT162b2 (B.1.1.7 + B.1.617.2) (Part B - Cohort 6). SR is defined as a ≥4-fold rise in neutralizing titer from baseline (pre IMP dose 1). For participants with a baseline titer less than the LLOQ, SR is defined as a post vaccination titer of ≥4 × LLOQ. Pre IMP dose 2 is also 3 weeks post dose 1 for Cohort 6.
Time frame: 1 month after Dose 2 and 1 month after Dose 3
Part B - GMTs of VOC in COVID-19 Vaccine-naïve Participants With and Without Evidence of Prior Infection in Part B C6 (1 and 2 Primary Doses Respectively) and in BNT162b2-Experienced Participants Without Evidence of Infection in Part B C1 (1 Booster Dose)
GMTs of VOC specific NTs (B.1.1.7, B.1.617.2, B.1.1.529.5 \[Omicron BA.5\]) 3 weeks after one dose of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 vaccine-naïve participants with evidence of prior infection (Cohort 6), 1 month after two doses of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 vaccine-naïve participants without evidence of infection (Cohort 6), and 1 month after one booster dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced participants without evidence of infection (Cohort 1). GMTs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5 × LLOQ; assay results above the ULOQ were set to ULOQ.
Time frame: Day 1 up to 1 month after 1 booster dose in Part B Cohort 1 without evidence of infection, up to 1 month after 2 doses in Part B Cohort 6 without evidence of infection and up to 3 weeks after 1 dose in Part B Cohort 6 with evidence of prior infection
Part B - GMRs of VOC in COVID-19 Vaccine-naïve Participants With and Without Evidence of Prior Infection (1 and 2 Primary Doses Respectively) and in BNT162b2-Experienced Participants Without Evidence of Infection (1 Booster Dose)
GMR of VOC specific NTs (B.1.1.7, B.1.617.2, B.1.1.529.5 \[Omicron BA.5\]) 3 weeks after one dose of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 vaccine-naïve participants with evidence of prior infection (Cohort 6) to the VOCs NTs 1 month after two doses of BNT162b2 (B.1.1.7 + B.1.617.2) in participants without evidence of infection (Cohort 6), and to the VOCs NTs 1 month after one booster dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced participants without evidence of infection (Cohort 1). GMRs and 2-sided 95% CIs were calculated by exponentiating the difference of the LS means and corresponding CIs based on the analysis of logarithmically transformed neutralizing titers using a linear regression model with terms of age, sex, and group. A separate model was fit for each comparison. Assay results below the LLOQ were set to 0.5 × LLOQ; assay results above the ULOQ were set to ULOQ.
Time frame: Day 1 to Day 29
Part B - Difference in SRs to VOCs in COVID-19 Vaccine-naïve Participants With and Without Evidence of Prior Infection (1 and 2 Primary Doses Respectively) and in BNT162b2-Experienced Participants Without Evidence of Infection (1 Booster Dose)
The difference in SRs to VOC specific NTs (B.1.1.7, B.1.617.2, B.1.1.529.5 \[Omicron BA.5\]) 3 weeks after one dose of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 vaccine-naïve participants with evidence of prior infection (Cohort 6) to those 1 month after two doses of BNT162b2 (B.1.1.7 + B.1.617.2) in participants without evidence of infection (Cohort 6), and to those 1 month after one booster dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced participants without evidence of infection (Cohort 1). Adjusted difference in proportions estimated using minimum risk weights and stratified by sex and age group (18 to 55 years, 56 to 85 years), expressed as a percentage. 2-Sided CI based on the Newcombe method stratified by sex and age group (18 to 55 years, 56 to 85 years) with minimum risk weights for the difference in proportions.
Time frame: Day 1 to Day 29
Part B - SR of VOC in COVID-19 Vaccine-naïve Participants With and Without Evidence of Prior Infection (1 and 2 Primary Doses Respectively) and in BNT162b2-Experienced Participants Without Evidence of Infection (1 Booster Dose)
SRs of VOC specific NTs (B.1.1.7, B.1.617.2, B.1.1.529.5 \[Omicron BA.5\]) 3 weeks after one dose of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 vaccine-naïve participants with evidence of prior infection (Cohort 6) 1 month after two doses of BNT162b2 (B.1.1.7 + B.1.617.2) in participants without evidence of infection (Cohort 6), and 1 month after one booster dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced participants without evidence of infection (Cohort 1). Seroresponse was defined as achieving a ≥4-fold rise from baseline. If the baseline measurement was below the LLOQ, a postvaccination assay result ≥4 × LLOQ was considered a seroresponse.
Time frame: 3 weeks after one dose in participants with evidence of prior infection (Cohort 6), 1 month after two doses in participants without evidence of infection (Cohort 6), and 1 month after one booster dose (Cohort 1)
Part C - GMT - B.1.1.529.1 in RNA Based COVID-19 Vaccine-experienced Participants With History of SARS-CoV-2 Infection
VOC NT in RNA-based COVID-19 vaccine-experienced participants with history of SARS-CoV-2 infection at baseline and 7 days, 1 month, and 3 months after the trial start for Cohorts 7, 8, and 9, and 6 and 12 months after the trial start for Cohorts 7 and 8. GMTs and 2-sided 95% CIs are calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ are set to 0.5 × LLOQ and above the ULOQ are set to ULOQ. Number of subjects with valid and determinate assay results for the specified variant at the given dose/sampling time point. No vaccination was given to Cohort 9 participants within 3 months after Visit 1. The term "post IMP" does not apply for Cohort 9 since no IMP was given, but blood was collected at the same timepoints post randomization.
Time frame: Day 1 to Day 360

Results

Posted Nov 22, 2024

Participant flow

Adult male and female participants were eligible if they had received two doses of the parent vaccine BNT162b2 at 30 µg, and the second dose of BNT162b2 was at least 6 months ago (Part A Cohorts 1 to 5, Part B Cohorts 1 and 4), or had not received prior Coronavirus Disease 2019 (COVID-19) vaccination (Part A Cohort 6, Part B Cohort 6) or had received 2 or 3 injections of any authorized COVID-19 RNA-based vaccine and were subsequently diagnosed with SARS-CoV-2 infection from January 2022 onwards

Participant flow — Overall Study
Milestone	Part A - Cohort 1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - Cohort 2: 2 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - Cohort 3: 1 Dose of 30 μg BNT162b2 (B.1.1.7)	Part A - Cohort 4: 1 Dose of 30 μg BNT162b2 (B.1.617.2)	Part A - Cohort 5: 1 Dose of 30 μg BNT162b2 (Original Vaccine)	Part A - Cohort 6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part B - Cohort 1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part B - Cohort 4: 1 Dose 30 μg BNT162b2 (B.1.617.2)	Part B - Cohort 6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part C - Cohort 7: 1 Dose of 30 μg BNT162b2 (B.1.1.529)	Part C - Cohort 8: 1 Dose of 30 μg BNT162b2 (Original Vaccine)	Part C - Cohort 9: No Vaccination
Started	21	20	20	20	42	17	349	352	361	72	71	35
Completed	14	10	15	12	29	13	280	291	299	60	55	30
Not completed	7	10	5	8	13	4	69	61	62	12	16	5
Withdrew: Withdrawal of consent	0	0	1	3	3	0	30	9	3	2	5	1
Withdrew: Lost to follow-up	2	4	2	3	5	2	15	12	38	6	6	0
Withdrew: Death	0	0	0	0	0	0	1	0	2	0	0	0
Withdrew: Physician decision	0	0	0	0	0	0	2	0	7	0	0	0
Withdrew: Withdrawal by subject	2	3	2	2	4	2	4	22	8	1	3	2
Withdrew: Protocol violation	2	3	0	0	1	0	16	18	2	2	2	1
Withdrew: Not further specified	1	0	0	0	0	0	1	0	2	1	0	1

Outcome measures

PrimaryAll Parts - Percentage of Participants Reporting Local Reactions at the Injection Site (Pain, Tenderness, Erythema/Redness, Induration/Swelling)

Local reactions of any grade are reported. Local reactions were graded using criteria based on the US FDA Guidance for Industry "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials"; the guidance uses the Grades 1 (mild), 2 (moderate), 3 (severe), and 4 (potentially life-threatening). The reporting of systemic reactions was based on the participant's assessments collected in the electronic diary (e-diary) or mapped from the adverse event case report form from Day 1 to Day 7 after each IMP dose. For Erythema/redness and Induration/swelling, the reported size had to be at least 2.5 cm to be deemed as a local reaction. Local reactions with a size less than 2.5 cm are not included in the analysis. Subjects in Cohort 9 did not receive a vaccination and are not included in this analysis.

Time frame:: from Day 1 to Day 7 after each IMP dose
Reported as:: Count of participants · Participants

All Parts - Percentage of Participants Reporting Local Reactions at the Injection Site (Pain, Tenderness, Erythema/Redness, Induration/Swelling)
Participants	Part A - Cohort 1: 1 Dose of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - Cohort 2: 2 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - Cohort 3: 1 Dose of 30 μg BNT162b2 (B.1.1.7)	Part A - Cohort 4: 1 Dose of 30 μg BNT162b2 (B.1.617.2)	Part A - Cohort 5: 1 Dose of 30 μg BNT162b2 (Original Vaccine)	Part A - Cohort 6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part B - Cohort 1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part B - Cohort 4: 1 Dose 30 μg BNT162b2 (B.1.617.2)	Part B - Cohort 6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part C - Cohort 7: 1 Dose of 30 μg BNT162b2 (B.1.1.529)	Part C - Cohort 8: 1 Dose of 30 μg BNT162b2 (Original Vaccine)	Part C - Cohort 9: No Vaccination
Any local reaction - Overall	19	20	17	19	37	15	290	310	261	63	61	—
Pain at the injection site - Overall	17	19	14	17	27	13	254	264	247	57	52	—
Tenderness - Overall	18	20	17	18	33	14	220	273	201	55	56	—
Erythema/redness - Overall	1	3	1	1	8	1	34	30	47	11	7	—
Induration/swelling - Overall	1	3	1	2	10	4	36	30	58	8	5	—
Any local reaction - After IMP Dose 1	19	20	17	19	37	12	290	310	213	63	61	—
Pain at the injection site - After IMP Dose 1	17	19	14	17	27	10	254	264	194	57	52	—
Tenderness - After IMP Dose 1	18	20	17	18	33	12	220	273	133	55	56	—
Erythema/redness - After IMP Dose 1	1	3	1	1	8	1	34	30	22	11	7	—
Induration/swelling - After IMP Dose 1	1	3	1	2	10	2	36	30	36	8	5	—
Any local reaction - After IMP Dose 2	—	12	—	—	—	10	—	—	153	—	—	—
Pain at the injection site - After IMP Dose 2	—	11	—	—	—	9	—	—	142	—	—	—
Tenderness - After IMP Dose 2	—	9	—	—	—	10	—	—	80	—	—	—
Erythema/redness - After IMP Dose 2	—	0	—	—	—	0	—	—	16	—	—	—
Induration/swelling - After IMP Dose 2	—	1	—	—	—	0	—	—	22	—	—	—
Any local reaction - After IMP Dose 3	—	—	—	—	—	8	—	—	169	—	—	—
Pain at the injection site - After IMP Dose 3	—	—	—	—	—	8	—	—	153	—	—	—
Tenderness - After IMP Dose 3	—	—	—	—	—	7	—	—	123	—	—	—
Erythema/redness - After IMP Dose 3	—	—	—	—	—	0	—	—	19	—	—	—
Induration/swelling - After IMP Dose 3	—	—	—	—	—	3	—	—	19	—	—	—

PrimaryAll Parts - Percentage of Participants Reporting Systemic Events (Fever, Fatigue, Headache, Chills, Vomiting, Nausea, Diarrhea, New or Worsened Muscle Pain, and New or Worsened Joint Pain)

Systemic reactions of any grade are reported. Systemic reactions were graded using criteria based on the guidance given in the US FDA Guidance for Industry "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials"; the guidance uses the Grades 1 (mild), 2 (moderate), 3 (severe), and 4 (potentially life-threatening). The reporting of systemic reactions was based on the participant's assessments collected in the e-diary or mapped from the adverse event case report form from Day 1 to Day 7 after each IMP dose. For Fever, the reported oral temperature had to be ≥38.0°C to be deemed as a systemic event. Oral temperature less than 38.0°C are not included in the analysis. Subjects in Cohort 9 did not receive a vaccination and are not included in this analysis.

Time frame:: from Day 1 to Day 7 after each IMP dose
Reported as:: Count of participants · Participants

All Parts - Percentage of Participants Reporting Systemic Events (Fever, Fatigue, Headache, Chills, Vomiting, Nausea, Diarrhea, New or Worsened Muscle Pain, and New or Worsened Joint Pain)
Participants	Part A - Cohort 1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - Cohort 2: 2 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - Cohort 3: 1 Dose of 30 μg BNT162b2 (B.1.1.7)	Part A - Cohort 4: 1 Dose of 30 μg BNT162b2 (B.1.617.2)	Part A - Cohort 5: 1 Dose of 30 μg BNT162b2 (Original Vaccine)	Part A - Cohort 6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part B - Cohort 1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part B - Cohort 4: 1 Dose 30 μg BNT162b2 (B.1.617.2)	Part B - Cohort 6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part C - Cohort 7: 1 Dose of 30 μg BNT162b2 (B.1.1.529)	Part C - Cohort 8: 1 Dose of 30 μg BNT162b2 (Original Vaccine)	Part C - Cohort 9: No Vaccination
Any systemic event - Overall	17	20	15	16	33	13	255	267	253	52	55	—
Fever: Oral temperature of ≥ 38.0℃ - Overall	4	5	3	2	0	1	32	34	34	1	3	—
Nausea - Overall	2	9	4	7	4	4	61	64	93	9	15	—
Vomiting - Overall	0	3	0	1	0	1	8	7	34	1	0	—
Diarrhea - Overall	2	5	3	2	6	4	19	39	68	8	10	—
Headache - Overall	15	17	12	8	22	10	160	178	190	32	35	—
Fatigue - Overall	15	19	15	15	30	9	219	220	180	40	44	—
Chills - Overall	10	13	3	9	13	7	91	115	77	11	14	—
New or worsened muscle pain - Overall	10	14	10	8	16	8	123	131	143	20	19	—
New or worsened joint pain - Overall	6	7	4	4	13	5	87	78	101	9	9	—
Any systemic event - After IMP Dose 1	17	18	15	16	33	11	255	267	203	52	55	—
Fever: Oral temperature of ≥ 38.0℃ - After IMP Dose 1	4	4	3	2	0	0	32	34	14	1	3	—
Nausea - After IMP Dose 1	2	6	4	7	4	3	61	64	58	9	15	—
Vomiting - After IMP Dose 1	0	1	0	1	0	1	8	7	22	1	0	—
Diarrhea - After IMP Dose 1	2	4	3	2	6	2	19	39	44	8	10	—
Headache - After IMP Dose 1	15	16	12	8	22	8	160	178	125	32	35	—
Fatigue - After IMP Dose 1	15	17	15	15	30	8	219	220	119	40	44	—
Chills - After IMP Dose 1	10	9	3	9	13	3	91	115	43	11	14	—
New or worsened muscle pain - After IMP Dose 1	10	12	10	8	16	6	123	131	92	20	19	—
New or worsened joint pain - After IMP Dose 1	6	6	4	4	13	3	87	78	68	9	9	—
Any systemic event - After IMP Dose 2	—	14	—	—	—	9	—	—	139	—	—	—
Fever: Oral temperature of ≥ 38.0℃ - After IMP Dose 2	—	1	—	—	—	1	—	—	12	—	—	—
Nausea - After IMP Dose 2	—	5	—	—	—	2	—	—	28	—	—	—
Vomiting - After IMP Dose 2	—	2	—	—	—	1	—	—	9	—	—	—
Diarrhea - After IMP Dose 2	—	2	—	—	—	2	—	—	20	—	—	—
Headache - After IMP Dose 2	—	11	—	—	—	6	—	—	88	—	—	—
Fatigue - After IMP Dose 2	—	13	—	—	—	6	—	—	77	—	—	—
Chills - After IMP Dose 2	—	6	—	—	—	3	—	—	29	—	—	—
New or worsened muscle pain - After IMP Dose 2	—	9	—	—	—	4	—	—	61	—	—	—
New or worsened joint pain - After IMP Dose 2	—	3	—	—	—	4	—	—	39	—	—	—
Any systemic event - After IMP Dose 3	—	—	—	—	—	6	—	—	142	—	—	—
Fever: Oral temperature of ≥ 38.0℃ - After IMP Dose 3	—	—	—	—	—	0	—	—	13	—	—	—
Nausea - After IMP Dose 3	—	—	—	—	—	1	—	—	33	—	—	—
Vomiting - After IMP Dose 3	—	—	—	—	—	0	—	—	12	—	—	—
Diarrhea - After IMP Dose 3	—	—	—	—	—	1	—	—	22	—	—	—
Headache - After IMP Dose 3	—	—	—	—	—	4	—	—	104	—	—	—
Fatigue - After IMP Dose 3	—	—	—	—	—	4	—	—	87	—	—	—
Chills - After IMP Dose 3	—	—	—	—	—	2	—	—	27	—	—	—
New or worsened muscle pain - After IMP Dose 3	—	—	—	—	—	4	—	—	54	—	—	—
New or worsened joint pain - After IMP Dose 3	—	—	—	—	—	2	—	—	28	—	—	—

PrimaryAll Parts - Percentage of Participants Reporting Adverse Events (AEs)

An AE is defined as TEAE if the event onset date and time is after the first IMP dose (if the event was absent before the first administration of the IMP) or worsened after the first IMP dose (if the event was present before the first administration of the IMP). In the event of an incomplete onset date, the event is considered as treatment-emergent unless the partial onset date information or complete or partial end date confirms the onset date or the event end prior to the first dose of IMP. Percentages for dose 1, dose 2, dose 3 and overall summaries are based upon the number of participants who received the respective IMP dose.

Time frame:: Dose 1 up to 1 month after each dose (all parts)
Reported as:: Number · percentage of participants

All Parts - Percentage of Participants Reporting Adverse Events (AEs)
percentage of participants	Part A - Cohort 1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - Cohort 2: 2 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - Cohort 3: 1 Dose of 30 μg BNT162b2 (B.1.1.7)	Part A - Cohort 4: 1 Dose of 30 μg BNT162b2 (B.1.617.2)	Part A - Cohort 5: 1 Dose of 30 μg BNT162b2 (Original Vaccine)	Part A - Cohort 6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part B - Cohort 1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part B - Cohort 4: 1 Dose 30 μg BNT162b2 (B.1.617.2)	Part B - Cohort 6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part C - Cohort 7: 1 Dose of 30 μg BNT162b2 (B.1.1.529)	Part C - Cohort 8: 1 Dose of 30 μg BNT162b2 (Original Vaccine)	Part C - Cohort 9: No Vaccination
Any AE after IMP Dose 1	19.0	30.0	30.0	15.0	66.7	29.4	14.6	13.1	20.2	12.5	19.7	—
Any AE after IMP Dose 2	—	27.8	—	—	—	17.6	—	—	15.7	—	—	—
Any AE after IMP Dose 3	—	—	—	—	—	20.0	—	—	15.2	—	—	—

PrimaryAll Parts - Percentage of Participants Reporting Serious Adverse Events (SAEs)

An SAE was any untoward medical occurrence that, at any dose: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent disability/ incapacity; was a congenital anomaly/birth defect and/or was another important medical event. SAEs from dose 1 up to 6 months post last IMP dose are presented. MedDRA (version 26.1) coding dictionary applied. An SAE is defined as TESAE if the event onset date and time is after the first IMP dose (if the event was absent before the first administration of the IMP) or worsened after the first IMP dose (if the event was present before the first administration of the IMP). In the event of an incomplete onset date, the event is considered as treatment-emergent unless the partial onset date information or complete or partial end date confirms the onset date or the event end prior to the first dose of IMP.

Time frame:: Dose 1 up to 6 months after the last dose
Reported as:: Number · Percentage of participants

All Parts - Percentage of Participants Reporting Serious Adverse Events (SAEs)
Percentage of participants	Part A - Cohort 1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - Cohort 2: 2 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - Cohort 3: 1 Dose of 30 μg BNT162b2 (B.1.1.7)	Part A - Cohort 4: 1 Dose of 30 μg BNT162b2 (B.1.617.2)	Part A - Cohort 5: 1 Dose of 30 μg BNT162b2 (Orginal Vaccine)	Part A - Cohort 6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part B - Cohort 1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part B - Cohort 4: 1 Dose 30 μg BNT162b2 (B.1.617.2)	Part B - Cohort 6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part C - Cohort 7: 1 Dose of 30 μg BNT162b2 (B.1.1.529)	Part C - Cohort 8: 1 Dose of 30 μg BNT162b2 (Original Vaccine)	Part C - Cohort 9: No Vaccination
All Parts - Percentage of Participants Reporting Serious Adverse Events (SAEs)	0	0	0	0	0	0	1.1	1.7	3.6	0	7.0	—

PrimaryPart B - GMR of B.1.1.7 NT 1 Month After 1 Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 (NCT04368728) Trial

GMRs and 2-sided 95% CIs were calculated by exponentiating the difference of least square means and corresponding CIs based on the analysis of logarithmically transformed neutralizing titers using a linear regression model with terms of age, sex, and vaccine group. The overall number of participants analyzed represents the number of participants with valid and determinate assay results for B.1.1.7 and reference strain respectively at the given dose/sampling time point within the specified window. GMR data are presented below as per the primary endpoint defined in the protocol. GMTs for the individual arms (from which GMR was derived) were secondary endpoints and are presented in outcome measure 22. GMR = Geometric mean ratio; NT = neutralizing titers

Time frame:: 1 month after booster dose in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial
Reported as:: Geometric mean · Titer ratio

Part B - GMR of B.1.1.7 NT 1 Month After 1 Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 (NCT04368728) Trial
Titer ratio	BNT162-17 Part B - Cohort 1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2) / C4591001 BNT162b2 30 μg
Part B - GMR of B.1.1.7 NT 1 Month After 1 Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 (NCT04368728) Trial	8.81 (7.49 to 10.36)

PrimaryPart B - GMR of B.1.617.2 NT 1 Month After 1 Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 (NCT04368728) Trial

GMRs and 2-sided 95% CIs were calculated by exponentiating the difference of least square means and corresponding CIs based on the analysis of logarithmically transformed neutralizing titers using a linear regression model with terms of age, sex, and group. The overall number of participants analyzed represents the number of participants with valid and determinate assay results for B.1.617.2 and reference strain respectively at the given dose/sampling time point within the specified window. GMR data are presented below as per the primary endpoint defined in the protocol. GMTs for the individual arms (from which GMR was derived) were secondary endpoints and are presented in outcome measure 22. GMR = Geometric mean ratio; NT = neutralizing titers

Time frame:: 1 month after booster dose in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial
Reported as:: Geometric mean · Titer ratio

Part B - GMR of B.1.617.2 NT 1 Month After 1 Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 (NCT04368728) Trial
Titer ratio	BNT162-17 Part B - Cohort 1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2) / C4591001 BNT162b2 30 μg
Part B - GMR of B.1.617.2 NT 1 Month After 1 Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 (NCT04368728) Trial	4.88 (4.19 to 5.68)

PrimaryPart B - GMR of B.1.617.2 NT 1 Month After 1 Dose of BNT162b2 (B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 (NCT04368728) Trial

GMRs and 2-sided 95% CIs were calculated by exponentiating the difference of least square means and corresponding CIs based on the analysis of logarithmically transformed neutralizing titers using a linear regression model with terms of age, sex, and group. The overall number of participants analyzed represents the number of participants with valid and determinate assay results for B.1.617.2 and reference strain respectively at the given dose/sampling time point within the specified window. GMR data are presented below as per the primary endpoint defined in the protocol. GMTs for the individual arms (from which GMR was derived) were secondary endpoints and are presented in outcome measure 24.

Time frame:: 1 month after booster dose in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial
Reported as:: Geometric mean · Titer ratio

Part B - GMR of B.1.617.2 NT 1 Month After 1 Dose of BNT162b2 (B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 (NCT04368728) Trial
Titer ratio	BNT162-17 Part B - Cohort 4: 1 Dose 30 μg BNT162b2 (B.1.617.2) / C4591001 BNT162b2 30 μg
Part B - GMR of B.1.617.2 NT 1 Month After 1 Dose of BNT162b2 (B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 (NCT04368728) Trial	6.40 (5.47 to 7.48)

PrimaryPart B - Difference in Seroresponse (SR) to B.1.1.7 NT 1 Month After 1 Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From C4591001 (NCT04368728)

Seroresponse was defined as a ≥4-fold rise in neutralizing titer from baseline. For subjects with a baseline titer less than the lower limit of quantitation (\<LLOQ), seroresponse was defined as a post-vaccination titer of ≥4× LLOQ. Adjusted difference was estimated using minimum risk weights and stratified by sex and age group (18 to 55 years, 56 to 85 years), expressed as a percentage. Associated 2-sided 95% CI based on the Newcombe method with minimum risk weights for the difference in proportions. Difference in seroresponse data are presented below as per the primary endpoint defined in the protocol. Seroresponses for the individual arms (from which the difference was derived) were secondary endpoints and are presented in outcome measure 23.

Time frame:: 1 month after booster dose in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial
Reported as:: Number · percentage difference

Part B - Difference in Seroresponse (SR) to B.1.1.7 NT 1 Month After 1 Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From C4591001 (NCT04368728)
percentage difference	BNT162-17 Part B - Cohort 1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2) - C4591001 BNT162b2 30 μg
Part B - Difference in Seroresponse (SR) to B.1.1.7 NT 1 Month After 1 Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From C4591001 (NCT04368728)	0.25 (-4.86 to 5.26)

PrimaryPart B - Difference in SR to B.1.617.2 NT 1 Month After 1 Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From C4591001 (NCT04368728)

Time frame:: 1 month after booster dose in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial
Reported as:: Number · percentage difference

Part B - Difference in SR to B.1.617.2 NT 1 Month After 1 Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From C4591001 (NCT04368728)
percentage difference	BNT162-17 Part B - Cohort 1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2) - C4591001 BNT162b2 30 μg
Part B - Difference in SR to B.1.617.2 NT 1 Month After 1 Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From C4591001 (NCT04368728)	-2.39 (-7.74 to 2.84)

PrimaryPart B - Difference in SR to B.1.617.2 NT 1 Month After 1 Dose of BNT162b2 (B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From C4591001 (NCT04368728)

Time frame:: 1 month after booster dose in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial
Reported as:: Number · percentage difference

Part B - Difference in SR to B.1.617.2 NT 1 Month After 1 Dose of BNT162b2 (B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From C4591001 (NCT04368728)
percentage difference	BNT162-17 Part B - Cohort 4: 1 Dose 30 μg BNT162b2 (B.1.617.2) / C4591001 BNT162b2 30 μg
Part B - Difference in SR to B.1.617.2 NT 1 Month After 1 Dose of BNT162b2 (B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From C4591001 (NCT04368728)	9.70 (5.68 to 13.97)

PrimaryPart B - GMR of B.1.1.7 NT 1 Month After 2 Doses of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 Vaccine-naïve Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the C4591001 (NCT04368728) Trial

Cohort B6 aimed to generate data to support a 2-dose primary regimen of alpha-delta multivalent BNT162b2 vaccine in SARS-CoV-2 naïve, unvaccinated individuals. The population recruited in Cohort B6, while complying with the inclusion criterium of no known history SARS-CoV-2 infection, were retrospectively seropositive for SARS-CoV-2 by planned N-binding antibody assessment of baseline samples. While the cohort was COVID-19 vaccine-naïve, it was not SARS-CoV-2-naïve as needed to match the control group (C4591001/NCT04368728). Procedurally, submission of a protocol amendment was not possible. However, the Statistical Analysis Plan was amended to describe that the non-inferiority analysis could not be performed according to the protocol. Control participants were not selected as planned; therefore, data were not available to calculate the GMR. Available GMT data for the 17 Cohort B6 participants without evidence of infection were analyzed and are presented in Outcome Measure 28.

Time frame:: 1 month

No measurements were reported for this outcome.

PrimaryPart B - GMR of B.1.617.2 NT 1 Month After 2 Doses of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 Vaccine-naïve Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the C4591001 (NCT04368728) Trial

Cohort B6 aimed to generate data to support a 2-dose primary regimen of alpha-delta multivalent BNT162b2 vaccine in SARS-CoV-2 naïve, unvaccinated individuals. The population recruited in Cohort B6, while complying with the inclusion criterium of no known history SARS-CoV-2 infection, were retrospectively seropositive for SARS-CoV-2 by planned N-binding antibody assessment of baseline samples. While the cohort was COVID-19 vaccine-naïve, it was not SARS-CoV-2-naïve as needed to match the control group (C4591001/NCT04368728). Procedurally, submission of a protocol amendment was not possible. However, the Statistical Analysis Plan was amended to describe that the non-inferiority analysis could not be performed according to the protocol. Control participants were not selected as planned; therefore, data were not available to calculate the GMR. Available GMT data for the 17 Part B Cohort 6 participants without evidence of infection were analyzed and are presented in Outcome Measure 28.

Time frame:: 1 month

No measurements were reported for this outcome.

PrimaryPart B - The Difference in SR to B.1.1.7 NT 1 Month After 2 Doses of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 Vaccine-naïve Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the C4591001 (NCT04368728) Trial

Cohort B6 aimed to generate data to support a 2-dose primary regimen of alpha-delta multivalent BNT162b2 vaccine in SARS-CoV-2 naïve, unvaccinated individuals. The population recruited in Cohort B6, while complying with the inclusion criterium of no known history SARS-CoV-2 infection, were retrospectively seropositive for SARS-CoV-2 by planned N-binding antibody assessment of baseline samples. While the cohort was COVID-19 vaccine-naïve, it was not SARS-CoV-2-naïve as needed to match the control group (C4591001/NCT04368728). Procedurally, submission of a protocol amendment was not possible. However, the Statistical Analysis Plan was amended to describe that non-inferiority analysis could not be performed according to the protocol. Control participants were not selected as planned; therefore, data were not available to calculate difference in SR. Available SR data for the 17 Part B Cohort 6 participants without evidence of infection were analyzed and presented in Outcome Measure 31.

Time frame:: 1 month

No measurements were reported for this outcome.

PrimaryPart B - The Difference in SR to B.1.617.2 NT 1 Month After 2 Doses of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 Vaccine-naïve Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the C4591001 (NCT04368728) Trial

Cohort B6 aimed to generate data to support a 2-dose primary regimen of alpha-delta multivalent BNT162b2 vaccine in SARS-CoV-2 naïve, unvaccinated individuals. The population recruited in Cohort B6, while complying with the inclusion criterium of no known history SARS-CoV-2 infection, were retrospectively seropositive for SARS-CoV-2 by planned N-binding antibody assessment of baseline samples. While the cohort was COVID-19 vaccine-naïve, it was not SARS-CoV-2-naïve as needed to match the control group (C4591001/NCT04368728). Procedurally, submission of a protocol amendment was not possible. However, the Statistical Analysis Plan was amended to describe that the non-inferiority analysis could not be performed according to the protocol. Control participants were not selected as planned; therefore data were not available to calculate difference in SR. Available SR data for the 17 Part B Cohort 6 participants without evidence of infection were analyzed and presented in Outcome Measure 31.

Time frame:: 1 month

No measurements were reported for this outcome.

PrimaryPart B - GMR of Reference Strain NT After One Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in Participants With Evidence of Prior Infection to the Reference Strain NT After 2 Doses of BNT162b2 in Participants Without Evidence of Infection

GMR of reference strain NT 3 weeks (3W) after one dose (PD1) of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 vaccine-naïve participants with evidence of prior infection to the reference strain NT 1 month after two doses of BNT162b2 in participants without evidence of infection (COVID-19 Vaccine-naïve Participants) from the Phase III trial C4591001 (NCT04368728). GMTs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and corresponding CIs (based on the Student t distribution). Assay results below LLOQ were set to 0.5 × LLOQ. GMTs of NTs are presented in the descriptive data section of this outcome measure. GMRs and 2-sided 95% CIs were calculated by exponentiating the difference of LS means and corresponding CIs based on the analysis of logarithmically transformed neutralizing titers using a linear regression model with terms of age, sex, and group. GMR data are presented in the statistical analysis section.

Time frame:: 3 weeks post Dose 1 in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial
Reported as:: Geometric mean · Titer

Part B - GMR of Reference Strain NT After One Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in Participants With Evidence of Prior Infection to the Reference Strain NT After 2 Doses of BNT162b2 in Participants Without Evidence of Infection
Titer	BNT162-17 - C6: 3 Doses 30μg BNT162b2 (B.1.1.7+B.1.617.2) With Evidence of Prior Infection 3W PD1	C4591001 BNT162b2 30 μg Without Evidence of Infection - 1 Month Post-Dose 2
Part B - GMR of Reference Strain NT After One Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in Participants With Evidence of Prior Infection to the Reference Strain NT After 2 Doses of BNT162b2 in Participants Without Evidence of Infection	17404.2 (15485.1 to 19561.1)	1328.1 (1183.1 to 1491.0)

Statistical analysis

BNT162-17 - C6: 3 Doses 30μg BNT162b2 (B.1.1.7+B.1.617.2) With Evidence of Prior Infection 3W PD1 vs C4591001 BNT162b2 30 μg Without Evidence of Infection - 1 Month Post-Dose 2 · Geometric mean ratio: 13.12 · 95% CI 11.14 to 15.45GMRs and 2-sided 95% CIs were based on the analysis of logarithmically transformed neutralizing titers using a linear regression model with terms of age, sex, and group.

PrimaryPart B - The Difference in SRs to the Reference Strain NT in Subjects With Evidence of Prior Infection and to the Reference Strain NT in Participants Without Evidence of Infection (COVID-19 Vaccine-naïve Participants)

The difference in SRs to the reference strain NT 3 weeks after one dose of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 vaccine-naïve participants with evidence of prior infection to the reference strain NT 1 month after two doses of BNT162b2 in participants without evidence of infection from the Phase III trial C4591001 (NCT04368728). SR was defined as achieving a ≥4-fold rise from baseline. If the baseline measurement was below the LLOQ, a post-vaccination assay result ≥4 × LLOQ was considered a SR. SR to the reference strain NTs are presented in the descriptive data section of this outcome measure. Adjusted difference in proportions was estimated using minimum risk weights and stratified by sex and age group (18 to 55 years, 56 to 85 years), expressed as a percentage. 2-Sided CI was based on the Newcombe method with minimum risk weights for the difference in proportions. Difference in SR data are presented in the statistical analysis section.

Time frame:: 3 weeks post Dose 1 in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial
Reported as:: Number · percentage of participants

Part B - The Difference in SRs to the Reference Strain NT in Subjects With Evidence of Prior Infection and to the Reference Strain NT in Participants Without Evidence of Infection (COVID-19 Vaccine-naïve Participants)
percentage of participants	BNT162-17 - C6: 3 Doses 30 μg BNT162b2 (B.1.1.7 + B.1.617.2) With Evidence of Prior Infection 3W PD1	C4591001 BNT162b2 30 μg Without Evidence of Infection - 1 Month Post-Dose 2
Part B - The Difference in SRs to the Reference Strain NT in Subjects With Evidence of Prior Infection and to the Reference Strain NT in Participants Without Evidence of Infection (COVID-19 Vaccine-naïve Participants)	85.8 (80.9 to 89.8)	90.5 (86.5 to 93.7)

Statistical analysis

BNT162-17 - C6: 3 Doses 30 μg BNT162b2 (B.1.1.7 + B.1.617.2) With Evidence of Prior Infection 3W PD1 vs C4591001 BNT162b2 30 μg Without Evidence of Infection - 1 Month Post-Dose 2 · Difference in percentages: -4.55 · 95% CI -10.04 to 0.83Adjusted difference in percentages were estimated using minimum risk weights and stratified by sex and age group.

PrimaryPart C - GMR of B.1.1.529.1 NT 1 Month After One Dose of BNT162b2 (B.1.1.529.1) in RNA-based COVID-19 Vaccine-experienced Participants With History of SARS-CoV-2 Infection to Those at 1 Month After One Dose of BNT162b2 for Cohorts 7 and 8.

GMRs and 2-sided 95% CIs were calculated by exponentiating the difference of least square means and corresponding CIs based on the analysis of logarithmically transformed neutralizing titers using a linear regression model with terms of age and number of prior doses. The overall number of participants analyzed represents the number of participants with valid and determinate assay results for B.1.1.529.1 at the given dose/sampling time point within the specified window. GMR data are presented below as per the primary endpoint defined in the protocol. GMTs for the individual arms (from which the difference was derived) were secondary endpoints and are presented in outcome measure 32.

Time frame:: 1 month after 1 dose of BNT162b2 or BNT162b2 (B.1.1.529.1)
Reported as:: Geometric mean · Titer ratio

Part C - GMR of B.1.1.529.1 NT 1 Month After One Dose of BNT162b2 (B.1.1.529.1) in RNA-based COVID-19 Vaccine-experienced Participants With History of SARS-CoV-2 Infection to Those at 1 Month After One Dose of BNT162b2 for Cohorts 7 and 8.
Titer ratio	Part C - Cohort 7: 1 Dose of 30 μg BNT162b2 / Cohort 8: 1 Dose of 30 μg BNT162b2
Part C - GMR of B.1.1.529.1 NT 1 Month After One Dose of BNT162b2 (B.1.1.529.1) in RNA-based COVID-19 Vaccine-experienced Participants With History of SARS-CoV-2 Infection to Those at 1 Month After One Dose of BNT162b2 for Cohorts 7 and 8.	0.94 (0.61 to 1.44)

PrimaryPart C - The Difference in SR of B.1.1.529.1 NT 1 Month After One Dose of BNT162b2 (B.1.1.529.1) in RNA-based COVID-19 Vaccine-experienced Participants With History of SARS-CoV-2 Infection to Those at 1 Month After One Dose of BNT162b2 for Cohorts 7 & 8.

SR was defined as a ≥4-fold rise in neutralizing titer from baseline. For participants with a baseline titer less than the lower limit of quantitation (\<LLOQ), SR was defined as a post-vaccination titer of ≥4× LLOQ. SR to the reference strain NTs are presented in the descriptive data section of this outcome measure. Adjusted difference was estimated using minimum risk weights and stratified by sex and age group (18 to 55 years, 56 to 85 years), expressed as a percentage. Associated 2-sided 95% CI were based on the Newcombe method with minimum risk weights for the difference in proportions. Difference in SR data are presented in the statistical analysis section.

Time frame:: 1 month after 1 dose of BNT162b2 or BNT162b2 (B.1.1.529.1)
Reported as:: Number · percentage of participants

Part C - The Difference in SR of B.1.1.529.1 NT 1 Month After One Dose of BNT162b2 (B.1.1.529.1) in RNA-based COVID-19 Vaccine-experienced Participants With History of SARS-CoV-2 Infection to Those at 1 Month After One Dose of BNT162b2 for Cohorts 7 & 8.
percentage of participants	Part C - Cohort 7: 1 Dose of 30 μg BNT162b2 (B.1.1.529)	Part C - Cohort 8: 1 Dose of 30 μg BNT162b2 Original Vaccine
Part C - The Difference in SR of B.1.1.529.1 NT 1 Month After One Dose of BNT162b2 (B.1.1.529.1) in RNA-based COVID-19 Vaccine-experienced Participants With History of SARS-CoV-2 Infection to Those at 1 Month After One Dose of BNT162b2 for Cohorts 7 & 8.	59.4 (46.4 to 71.5)	22.8 (12.7 to 35.8)

Statistical analysis

Part C - Cohort 7: 1 Dose of 30 μg BNT162b2 (B.1.1.529) vs Part C - Cohort 8: 1 Dose of 30 μg BNT162b2 Original Vaccine · Difference in percentages: 36.73 · 95% CI 19.21 to 51.17Adjusted difference was estimated using the minimum risk weights and stratified by sex and age group.

SecondaryPart A - Geometric Mean Titer (GMT) at Each Timepoint

For BNT162b2-experienced participants (defined as participants who have previously received two injections of 30 μg BNT162b2). Reference and variant(s) of concern (VOC) specific NT. GMTs and 2-sided 95% CIs are calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ are set to 0.5 × LLOQ and above the ULOQ are set to ULOQ. Cohorts 1, 3, 4 and 5 received only 1 dose of IMP. Cohort 2 received dose 2 on Day 56 and did not receive dose 3. Cohort 6 received dose 2 on Day 21 and received dose 3 approximately 6 months after dose 2.

Time frame:: Day 1 up to Day 421
Reported as:: Geometric mean · Titer

Part A - Geometric Mean Titer (GMT) at Each Timepoint
Titer	Part A - Cohort 1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - Cohort 2: 2 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - Cohort 3: 1 Dose of 30 μg BNT162b2 (B.1.1.7)	Part A - Cohort 4: 1 Dose of 30 μg BNT162b2 (B.1.617.2)	Part A - Cohort 5: 1 Dose of 30 μg BNT162b2 (Orginal Vaccine)	Part A - Cohort 6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)
Pre IMP dose 1 - B.1.1.7	18.9 (9.0 to 39.7)	26.9 (14.5 to 49.9)	17.4 (9.0 to 33.8)	48.4 (20.0 to 117.0)	9.6 (5.2 to 17.8)	6.9 (4.6 to 10.5)
1-week post IMP dose 1 - B.1.1.7	1403.9 (817.9 to 2409.8)	1340.5 (731.0 to 2458.2)	1090.8 (701.7 to 1695.5)	557.2 (365.4 to 849.4)	307.9 (209.1 to 453.5)	30.2 (6.8 to 133.1)
3-weeks post IMP dose 1 - B.1.1.7	1035.7 (659.9 to 1625.5)	1168.4 (756.8 to 1803.9)	956.0 (657.3 to 1390.4)	493.5 (365.0 to 667.3)	361.6 (223.9 to 584.2)	—
1-month post IMP dose 1 - B.1.1.7	942.8 (552.6 to 1608.3)	1004.3 (705.3 to 1430.0)	1009.8 (697.8 to 1461.3)	468.5 (308.6 to 711.2)	314.5 (182.7 to 541.3)	—
6-months post IMP dose 1 - B.1.1.7	156.6 (62.5 to 392.2)	—	352.3 (192.4 to 645.3)	151.5 (68.9 to 333.1)	85.7 (36.9 to 199.3)	—
12-months post IMP dose 1 - B.1.1.7	658.8 (385.8 to 1124.7)	—	463.9 (180.0 to 1195.5)	241.0 (95.1 to 611.0)	463.9 (188.0 to 1144.8)	—
Pre IMP dose 2 - B.1.1.7	—	151 (49.1 to 464.5)	—	—	—	42.7 (12.5 to 145.9)
1-week post IMP dose 2 - B.1.1.7	—	987.0 (495.9 to 1964.4)	—	—	—	207.5 (104.3 to 413.0)
1-month post IMP dose 2 - B.1.1.7	—	958.9 (586.3 to 1568.3)	—	—	—	216.1 (101.7 to 459.0)
6-months post IMP dose 2 - B.1.1.7	—	349.0 (166.5 to 731.6)	—	—	—	—
12-months post IMP dose 2 - B.1.1.7	—	940.6 (480.4 to 1841.7)	—	—	—	—
6-months post IMP dose 2 + pre IMP dose 3 - B.1.1.7	—	—	—	—	—	68.3 (21.7 to 215.2)
1-week post IMP dose 3 - B.1.1.7	—	—	—	—	—	640.0 (379.2 to 1080.2)
1-month post IMP dose 3 - B.1.1.7	—	—	—	—	—	562.0 (190.2 to 1660.6)
12-months post IMP dose 2 + 6-months post IMP dose 3 - B1.1.7	—	—	—	—	—	351.7 (162.4 to 761.8)
Pre IMP dose 1 - B.1.617.2	9.0 (4.8 to 16.7)	8.7 (5.1 to 15.0)	12.1 (6.4 to 22.8)	8.7 (6.0 to 12.6)	9.0 (5.2 to 15.8)	6.5 (4.7 to 9.0)
1-week post IMP dose 1 - B.1.617.2	526.6 (305.8 to 906.9)	385.0 (255.6 to 579.8)	517.1 (330.1 to 809.9)	359.2 (237.3 to 543.7)	254.0 (162.5 to 396.9)	27.7 (6.6 to 115.4)
3-weeks post IMP dose 1 - B.1.617.2	452.5 (283.1 to 723.5)	384.0 (251.0 to 587.6)	533.3 (368.0 to 772.7)	380.5 (265.8 to 544.8)	221.7 (123.0 to 399.6)	—
1-month post IMP dose 1 - B.1.617.2	369.1 (209.3 to 650.8)	303.8 (199.2 to 463.2)	486.8 (349.2 to 678.6)	288.4 (199.5 to 417.0)	207.5 (126.3 to 340.8)	—
6-months post IMP dose 1 - B.1.617.2	137.5 (51.6 to 366.1)	—	217.7 (127.9 to 370.5)	123.9 (55.3 to 277.7)	35.6 (17.5 to 72.7)	—
12-months post IMP dose 1 - B.1.617.2	640.0 (293.4 to 1396.1)	—	199.9 (87.3 to 458.1)	212.5 (78.3 to 576.2)	226.3 (92.5 to 553.7)	—
Pre IMP dose 2 - B.1.617.2	—	235.2 (144.0 to 384.1)	—	—	—	60.4 (18.3 to 199.5)
1-week post IMP dose 2 - B.1.617.2	—	515.4 (342.7 to 774.9)	—	—	—	216.7 (134.6 to 348.7)
1-month post IMP dose 2 - B.1.617.2	—	517.8 (366.6 to 731.5)	—	—	—	320.0 (139.1 to 736.4)
6-months post IMP dose 2 - B.1.617.2	—	226.3 (114.9 to 445.6)	—	—	—	—
12-months post IMP dose 2 - B.1.617.2	—	508.0 (288.7 to 893.9)	—	—	—	—
6-months post IMP dose 2 + pre IMP dose 3 - B.1.617.2	—	—	—	—	—	87.9 (26.2 to 294.9)
1-week post IMP dose 3 - B.1.617.2	—	—	—	—	—	819.8 (353.1 to 1903.2)
1-month post IMP dose 3 - B.1.617.2	—	—	—	—	—	640.0 (207.3 to 1976.3)
12-months post dose 2 + 6-months post dose 3 - B.1.617.2	—	—	—	—	—	424.9 (213.3 to 846.5)
Pre IMP dose 1 - Reference strain	14.9 (8.5 to 26.2)	18.7 (10.4 to 33.4)	18.3 (10.1 to 33.3)	27.8 (16.6 to 46.5)	14.1 (7.9 to 25.3)	6.8 (4.6 to 9.9)
1-week post IMP dose 1 - Reference strain	812.2 (474.1 to 1391.3)	519.8 (321.6 to 840.2)	640.0 (417.4 to 981.4)	702.0 (432.7 to 1138.7)	352.3 (238.3 to 521.0)	25.4 (6.6 to 97.7)
3-weeks post IMP dose 1 - Reference strain	678.1 (406.0 to 1132.3)	584.2 (357.5 to 954.8)	740.6 (495.0 to 1107.8)	748.0 (500.2 to 1118.6)	408.7 (262.0 to 637.4)	—
1-month post IMP dose 1 - Reference strain	589.9 (376.9 to 923.1)	452.5 (283.5 to 722.4)	688.4 (467.0 to 1014.9)	748.0 (469.3 to 1192.3)	380.5 (232.0 to 624.3)	—
6-months post IMP dose 1 - Reference strain	163.5 (72.7 to 367.7)	—	244.4 (143.8 to 415.4)	101.4 (57.8 to 178.0)	78.2 (42.2 to 145.0)	—
12-months post IMP dose 1 - Reference strain	604.1 (311.3 to 1172.1)	—	380.5 (164.8 to 878.9)	170.4 (67.6 to 429.5)	565.5 (244.1 to 1310.2)	—
Pre IMP dose 2 - Reference strain	—	387.9 (227.7 to 660.9)	—	—	—	37.5 (11.3 to 124.6)
1-week post IMP dose 2 - Reference strain	—	697.9 (453.5 to 1074.1)	—	—	—	95.1 (59.8 to 151.4)
1-month post IMP dose 2 - Reference strain	—	665.1 (400.1 to 1105.6)	—	—	—	136.1 (58.1 to 319.0)
6-months post IMP dose 2 - Reference strain	—	334.2 (171.5 to 651.2)	—	—	—	—
12-months post IMP dose 2 - Reference strain	—	527.9 (263.8 to 1056.2)	—	—	—	—
6-months post IMP dose 2 + pre IMP dose 3 - Reference strain	—	—	—	—	—	53.1 (16.4 to 172.4)
1-week post IMP dose 3 - Reference strain	—	—	—	—	—	551.7 (299.8 to 1015.1)
1-month post IMP dose 3 - Reference strain	—	—	—	—	—	493.5 (195.5 to 1245.8)
12-months post dose 2 + 6-months post dose 3 - Reference strain	—	—	—	—	—	205.9 (80.1 to 528.8)

SecondaryPart A - Geometric Mean Fold Rises (GMFR) From Before Vaccination to Each Subsequent Time Point After Vaccination

For BNT162b2-experienced participants (defined as participants who have previously received two injections of 30 μg BNT162b2). Reference and VOC specific NT. GMFR is calculated as the mean of the difference of logarithmically transformed neutralization titers or antibody levels (later result minus earlier result) and exponentiating the mean. The associated 2-sided 95% CIs are obtained by constructing CIs using Student's t-distribution for the mean difference on the natural log scale and exponentiating the confidence limits. Assay results below the LLOQ are set to 0.5 × LLOQ and above the ULOQ are set to ULOQ. Cohorts 1, 3, 4 and 5 received only 1 dose of IMP. Cohort 2 received dose 2 on Day 56 and did not receive dose 3. Cohort 6 received dose 2 on Day 21 and received dose 3 approximately 6 months after dose 2.

Time frame:: Day 1 to Day 421
Reported as:: Geometric mean · Fold rise

Part A - Geometric Mean Fold Rises (GMFR) From Before Vaccination to Each Subsequent Time Point After Vaccination
Fold rise	Part A - Cohort 1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - Cohort 2: 2 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - Cohort 3: 1 Dose of 30 μg BNT162b2 (B.1.1.7)	Part A - Cohort 4: 1 Dose of 30 μg BNT162b2 (B.1.617.2)	Part A - Cohort 5: 1 Dose of 30 μg BNT162b2 (Orginal Vaccine)	Part A - Cohort 6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)
1-week post IMP dose 1 - B.1.1.7	68.6 (30.4 to 155.0)	78.8 (38.9 to 159.7)	95.5 (72.0 to 126.5)	13.0 (5.8 to 28.9)	31.4 (19.1 to 51.4)	4.8 (1.2 to 18.9)
3-weeks post IMP dose 1 - B.1.1.7	52.8 (28.4 to 98.2)	39.8 (23.3 to 68.0)	51.4 (30.3 to 87.3)	10.2 (4.8 to 21.9)	35.7 (20.6 to 61.6)	—
1-month post IMP dose 1 - B.1.1.7	48.1 (24.8 to 93.2)	37.4 (22.8 to 61.4)	54.3 (31.9 to 92.5)	9.7 (3.8 to 24.8)	27.7 (14.0 to 55.2)	—
6-months post IMP dose 1 - B.1.1.7	7.2 (2.9 to 18.0)	—	18.7 (8.2 to 42.5)	2.9 (0.9 to 9.6)	9.0 (3.7 to 22.0)	—
12-months post IMP dose 1 - B.1.1.7	21.1 (4.6 to 96.4)	—	20.5 (6.2 to 68.2)	4.0 (0.5 to 33.3)	36.3 (13.8 to 95.5)	—
Pre IMP dose 2 - B.1.1.7	—	6.2 (2.4 to 15.9)	—	—	—	6.2 (2.2 to 17.4)
1-week post IMP dose 2 - B.1.1.7	—	64.0 (37.4 to 109.4)	—	—	—	41.5 (20.9 to 82.6)
1-month post IMP dose 2 - B.1.1.7	—	39.5 (22.2 to 70.6)	—	—	—	33.6 (17.9 to 63.3)
6-months post IMP dose 2 - B.1.1.7	—	15.7 (7.4 to 33.2)	—	—	—	—
12-months post IMP dose 2 - B.1.1.7	—	22.6 (6.7 to 76.7)	—	—	—	—
6-months post IMP dose 2 + pre IMP dose 3 - B.1.1.7	—	—	—	—	—	12.4 (4.3 to 35.8)
1-week post IMP dose 3 - B.1.1.7	—	—	—	—	—	105.0 (76.8 to 143.6)
1-month post IMP dose 3 - B.1.1.7	—	—	—	—	—	82.0 (32.1 to 209.5)
12-months post dose 2 + 6-months post dose 3 - B.1.1.7	—	—	—	—	—	53.8 (25.6 to 113.0)
1-week post IMP dose 1 - B.1.617.2	52.7 (28.1 to 98.8)	64.0 (43.6 to 93.9)	73.1 (51.1 to 104.6)	35.9 (21.7 to 59.6)	27.2 (16.3 to 45.4)	4.9 (1.2 to 19.5)
3-weeks post IMP dose 1 - B.1.617.2	48.9 (28.4 to 84.2)	42.8 (27.6 to 66.5)	42.1 (26.2 to 67.6)	43.7 (27.1 to 70.6)	22.6 (12.3 to 41.7)	—
1-month post IMP dose 1 - B.1.617.2	40.9 (23.4 to 71.5)	34.9 (23.5 to 51.7)	38.4 (22.1 to 66.7)	33.1 (22.4 to 49.1)	20.0 (11.7 to 34.2)	—
6-months post IMP dose 1 - B.1.617.2	13.8 (5.3 to 35.6)	—	16.3 (8.1 to 32.9)	14.3 (5.8 to 35.4)	4.4 (1.9 to 9.9)	—
12-months post IMP dose 1 - B.1.617.2	42.2 (10.5 to 169.8)	—	12.8 (4.4 to 37.4)	21.9 (5.2 to 93.3)	19.3 (6.9 to 54.0)	—
Pre IMP dose 2 - B.1.617.2	—	27.4 (16.8 to 44.7)	—	—	—	9.3 (3.2 to 27.5)
1-week post IMP dose 2 - B.1.617.2	—	86.7 (53.9 to 139.5)	—	—	—	43.3 (26.9 to 69.7)
1-month post IMP dose 2 - B.1.617.2	—	60.4 (32.9 to 110.8)	—	—	—	55.2 (24.0 to 126.9)
6-months post IMP dose 2 - B.1.617.2	—	26.9 (11.7 to 62.0)	—	—	—	—
12-months post IMP dose 2 - B.1.617.2	—	34.6 (8.1 to 146.7)	—	—	—	—
6-months post IMP dose 2 + pre IMP dose 3 - B.1.617.2	—	—	—	—	—	16.5 (5.0 to 54.5)
1-week post IMP dose 3 - B.1.617.2	—	—	—	—	—	121.8 (63.4 to 233.9)
1-month post IMP dose 3 - B.1.617.2	—	—	—	—	—	86.1 (28.2 to 263.2)
12-months post dose 2 + 6-months post dose 3 - B.1.617.2	—	—	—	—	—	61.8 (30.8 to 124.0)
1-week post IMP dose 1 - Reference strain	52.7 (33.3 to 83.2)	39.4 (21.6 to 71.9)	50.3 (38.7 to 65.4)	20.6 (11.0 to 38.7)	23.1 (15.8 to 33.8)	4.1 (1.3 to 13.3)
3-weeks post IMP dose 1 - Reference strain	46.1 (28.1 to 75.8)	29.2 (18.3 to 46.7)	37.7 (22.0 to 64.8)	26.9 (15.6 to 46.3)	26.3 (16.5 to 42.0)	—
1-month post IMP dose 1 - Reference strain	40.9 (26.8 to 62.3)	24.3 (15.0 to 39.1)	36.4 (20.8 to 63.7)	26.9 (15.9 to 45.6)	23.1 (14.7 to 36.3)	—
6-months post IMP dose 1 - Reference strain	10.5 (5.1 to 21.5)	—	12.5 (6.1 to 25.4)	3.7 (1.8 to 7.5)	5.2 (2.9 to 9.2)	—
12-months post IMP dose 1 - Reference strain	29.9 (9.2 to 97.1)	—	17.7 (6.6 to 47.4)	6.0 (1.4 to 25.1)	26.5 (11.1 to 63.4)	—
Pre IMP dose 2 - Reference strain	—	21.8 (12.8 to 37.2)	—	—	—	5.5 (2.0 to 15.1)
1-week post IMP dose 2 - Reference strain	—	66.8 (27.7 to 161.5)	—	—	—	19.0 (12.0 to 30.3)
1-month post IMP dose 2 - Reference strain	—	37.3 (21.6 to 64.6)	—	—	—	21.5 (10.5 to 44.2)
6-months post IMP dose 2 - Reference strain	—	18.6 (9.1 to 38.0)	—	—	—	—
12-months post IMP dose 2 - Reference strain	—	21.0 (5.3 to 83.5)	—	—	—	—
6-months post IMP dose 2 + pre IMP dose 3 - Reference strain	—	—	—	—	—	10.0 (3.3 to 30.2)
1-week post IMP dose 3 - Reference strain	—	—	—	—	—	82.0 (52.7 to 127.6)
1-month post IMP dose 3 - Reference strain	—	—	—	—	—	74.2 (34.7 to 158.7)
12-months post dose 2 + 6-months post dose 3 - Reference strain	—	—	—	—	—	32.0 (10.8 to 95.2)

SecondaryPart A - Percentage of Participants Achieving SR in Terms of NT at Each Post Vaccination Time Point

For BNT162b2-experienced participants (defined as participants who have previously received two injections of 30 μg BNT162b2). Reference and VOC specific NT. SR is defined as a ≥4-fold rise in neutralizing titer from baseline (pre IMP dose 1). For subjects with a baseline titer less than the LLOQ, SR is defined as a post-vaccination titer of ≥4 × LLOQ. Pre IMP dose 2 is also 2 months post dose 1 for Cohort 2 and 3 weeks post dose 1 for Cohort 6. Cohorts 1, 3, 4 and 5 received only 1 dose of IMP. Cohort 2 received dose 2 on Day 56 and did not receive dose 3. Cohort 6 received dose 2 on Day 21 and received dose 3 approximately 6 months after dose 2.

Time frame:: Day 1 to Day 421
Reported as:: Number · Percentage of participants

Part A - Percentage of Participants Achieving SR in Terms of NT at Each Post Vaccination Time Point
Percentage of participants	Part A - Cohort 1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - Cohort 2: 2 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - Cohort 3: 1 Dose of 30 μg BNT162b2 (B.1.1.7)	Part A - Cohort 4: 1 Dose of 30 μg BNT162b2 (B.1.617.2)	Part A - Cohort 5: 1 Dose of 30 μg BNT162b2 (Orginal Vaccine)	Part A - Cohort 6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)
1-week post IMP dose 1 - B.1.1.7	93.3	100	100	66.7	94.1	33.3
3-weeks post IMP dose 1 - B.1.1.7	94.4	94.7	94.7	65.0	100.0	—
1-month post IMP dose 1 - B.1.1.7	94.1	95.0	100	65.0	88.2	—
6-months post IMP dose 1 - B.1.1.7	64.3	—	83.3	47.4	75.0	—
12-months post IMP dose 1 - B.1.1.7	80.0	—	64.3	54.5	90.9	—
Pre IMP dose 2 - B.1.1.7	—	61.1	—	—	—	43.8
1-week post IMP dose 2 - B.1.1.7	—	100	—	—	—	100.0
1-month post IMP dose 2 - B.1.1.7	—	94.4	—	—	—	92.9
6-months post IMP dose 2 + pre IMP dose 3 - B.1.1.7	—	—	—	—	—	63.6
1-week post IMP dose 3 - B.1.1.7	—	—	—	—	—	100.0
1-month post IMP dose 3 - B.1.1.7	—	—	—	—	—	100.0
6-months post IMP dose 2 - B.1.1.7	—	87.5	—	—	—	—
12-months post dose 2 + 6-months post dose 3 - B.1.1.7	—	—	—	—	—	100.0
12-months post IMP dose 2 - B.1.1.7	—	88.9	—	—	—	—
1-week post IMP dose 1 - B.1.617.2	93.8	100.0	100.0	100.0	88.2	33.3
3-weeks post IMP dose 1 - B.1.617.2	94.4	94.7	100.0	100.0	93.8	—
1-month post IMP dose 1 - B.1.617.2	100.0	95.0	94.7	100.0	88.2	—
6-months post IMP dose 1 - B.1.617.2	78.6	—	88.9	73.7	58.3	—
12-months post IMP dose 1 - B.1.617.2	90.0	—	57.1	81.8	81.8	—
Pre IMP dose 2 - B.1.617.2	—	94.4	—	—	—	56.3
1-week post IMP dose 2 - B.1.617.2	—	100	—	—	—	100
1-month post IMP dose 2 - B.1.617.2	—	94.4	—	—	—	92.9
6-months post IMP dose 2 + pre IMP dose 3 - B.1.617.2	—	—	—	—	—	72.7
1-week post IMP dose 3 - B.1.617.2	—	—	—	—	—	100.0
1-month post IMP dose 3 - B.1.617.2	—	—	—	—	—	100.0
6-months post IMP dose 2 - B.1.617.2	—	81.3	—	—	—	—
12-months post dose 2 + 6-months post dose 3 - B.1.617.2	—	—	—	—	—	100
12-months post IMP dose 2 - B.1.617.2	—	88.9	—	—	—	—
1-week post IMP dose 1 - Reference strain	100	100.0	100.0	86.7	94.1	33.3
3-weeks post IMP dose 1 - Reference strain	100	100.0	94.7	95.0	100.0	—
1-month post IMP dose 1 - Reference strain	100	95.0	94.7	95.0	100.0	—
6-months post IMP dose 1 - Reference strain	64.3	—	83.3	36.8	58.3	—
12-months post IMP dose 1 - Reference strain	90.0	—	85.7	54.5	90.9	—
Pre IMP dose 2 - Reference strain	—	94.4	—	—	—	43.8
1-week post IMP dose 2 - Reference strain	—	100.0	—	—	—	100.0
1-month post IMP dose 2 - Reference strain	—	100.0	—	—	—	85.7
6-months post IMP dose 2 + pre IMP dose 3 - Reference strain	—	—	—	—	—	54.5
1-week post IMP dose 3 - Reference strain	—	—	—	—	—	100.0
1-month post IMP dose 3 - Reference strain	—	—	—	—	—	100.0
6-months post IMP dose 2 - Reference strain	—	93.8	—	—	—	—
12-months post dose 2 + 6-months post dose 3 - Reference strain	—	—	—	—	—	100.0
12-months post IMP dose 2 - Reference strain	—	88.9	—	—	—	—

SecondaryPart B - GMT of VOCs and Reference Strains in Part B Cohort 1 and Control

GMTs of VOCs (B.1.1.7 and B.1.617.2) and reference strain 1 month after 1 dose of BNT162 (B.1.1.7+B.1.167.2) in participants from Part B Cohort 1 of the BNT162-17 trial (BNT162b2-experienced participants), and reference strain 1 month after 2 doses of BNT162b2 in selected participants from the Phase III C4591001 (NCT04368728) trial. GMTs and 2-sided 95% CIs are calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ are set to 0.5 × LLOQ and above the ULOQ are set to ULOQ.

Time frame:: 1 month after booster dose in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial
Reported as:: Geometric mean · Titer

Part B - GMT of VOCs and Reference Strains in Part B Cohort 1 and Control
Titer	BNT162-17 Part B - Cohort 1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	C4591001 BNT162b2 30 μg
B.1.1.7	996.5 (880.3 to 1128.0)	74.7 (66.1 to 84.3)
B.1.617.2	552.4 (495.2 to 616.2)	65.2 (57.5 to 74.0)
Reference strain	947.0 (846.4 to 1059.5)	113.3 (101.4 to 126.5)

SecondaryPart B - SR of of VOCs and Reference Strains in Part B Cohort 1 and Control

Percentage of participants achieving SR at 1 month after 1 dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced participants (Cohort 1) and 1 month after 2 doses of BNT162b2 primary series (participants from C4591001 \[NCT04368728\]). SR is defined as a ≥4-fold rise in neutralizing titer from baseline (pre IMP dose 1). For participants with a baseline titer less than the LLOQ, SR is defined as a post-vaccination titer of ≥4 × LLOQ.

Time frame:: 1 month after Dose 1 in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial
Reported as:: Number · Percentage of participants

Part B - SR of of VOCs and Reference Strains in Part B Cohort 1 and Control
Percentage of participants	Part B - Cohort 1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	C4591001 BNT162b2 30 μg
B.1.1.7	88.6 (84.4 to 92.0)	76.2 (71.3 to 80.7)
B.1.617.2	85.9 (81.4 to 89.6)	74.4 (69.3 to 79.0)
Reference strain	89.6 (85.6 to 92.8)	88.3 (84.3 to 91.5)

SecondaryPart B - GMT of VOCs and Reference Strains in Part B Cohort 4 and Control

GMTs of VOCs (B.1.617.2) and reference strain 1 month after 1 dose of BNT162 (B.1.167.2) in participants from Part B Cohort 4 of the BNT162-17 trial (BNT162b2-experienced participants), and 1 month after 2 doses of BNT162b2 in selected participants from the Phase III C4591001 (NCT04368728) trial. GMTs and 2-sided 95% CIs are calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ are set to 0.5 × LLOQ and above the ULOQ are set to ULOQ.

Time frame:: 1 month after booster dose in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial
Reported as:: Geometric mean · Titer

Part B - GMT of VOCs and Reference Strains in Part B Cohort 4 and Control
Titer	Part B - Cohort 4 - 1 Dose 30 μg BNT162b2 (B.1.617.2)	C4591001 BNT162b2 30 μg
B.1.1.7	972.8 (875.3 to 1081.1)	78.6 (69.6 to 88.8)
B.1.617.2	730.5 (654.5 to 815.3)	71.2 (62.7 to 80.8)
Reference strain	1005.3 (900.3 to 1122.5)	113.0 (100.5 to 127.1)

SecondaryPart B - SR of of VOCs and Reference Strains in Part B Cohort 4 and Control

Percentage of participants achieving SR at 1 month after 1 dose of BNT162b2 (B.1.617.2) in BNT162b2-experienced subjects (Part B - Cohort 4) and 1 month after 2 doses of BNT162b2 primary series (participants from C4591001 \[NCT04368728\]). SR is defined as a ≥4-fold rise in neutralizing titer from baseline (pre IMP dose 1). For participants with a baseline titer less than the LLOQ, SR is defined as a post-vaccination titer of ≥4 × LLOQ.

Time frame:: 1 month after Dose 1 in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial
Reported as:: Number · Percentage of participants

Part B - SR of of VOCs and Reference Strains in Part B Cohort 4 and Control
Percentage of participants	Part B - Cohort 4 - 1 Dose 30 μg BNT162b2 (B.1.617.2)	C4591001 BNT162b2 30 μg
B.1.1.7	96.5 (93.8 to 98.2)	78.4 (73.5 to 82.8)
B.1.617.2	97.4 (95.0 to 98.9)	77.5 (72.5 to 82.0)
Reference strain	98.1 (95.9 to 99.3)	87.5 (83.4 to 90.9)

SecondaryPart B - GMT of VOCs and Reference Strain in Part B Cohort 6 1 Month After Dose 2 and 1 Month After Dose 3

GMTs of VOCs and reference strain NT 1 month after dose 2 and dose 3 of BNT162b2 (B.1.1.7 + B.1.617.2) (Part B - Cohort 6). GMTs and 2-sided 95% CIs are calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ are set to 0.5 × LLOQ and above the ULOQ are set to ULOQ.

Time frame:: 1 month after Dose 2 and 1 month after Dose 3
Reported as:: Geometric mean · Titer

Part B - GMT of VOCs and Reference Strain in Part B Cohort 6 1 Month After Dose 2 and 1 Month After Dose 3
Titer	Part B - Cohort 6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.6172)
1 month post IMP dose 2 - B.1.1.7	832.5 (718.2 to 965.0)
1 month post IMP dose 3 - B.1.1.7	942.6 (836.4 to 1062.4)
1 month post IMP dose 2 - B.1.617.2	1184.6 (1015.5 to 1381.9)
1 month post IMP dose 3 - B.1.617.2	1270.9 (1130.2 to 1429.0)
1 month post IMP dose 2 - Reference strain	697.5 (594.0 to 819.1)
1 month post IMP dose 3 - Reference strain	830.5 (736.3 to 936.8)

SecondaryPart B - Cohort 6 - Percentages With SRs to VOCs (B.1.1.7, B.1.617.2) and Reference Strain

Percentage of participants achieving SR to VOCs (B.1.1.7, B.1.617.2) and reference strain at 1 month after dose 2 and dose 3 of BNT162b2 (B.1.1.7 + B.1.617.2) (Part B - Cohort 6). SR is defined as a ≥4-fold rise in neutralizing titer from baseline (pre IMP dose 1). For participants with a baseline titer less than the LLOQ, SR is defined as a post vaccination titer of ≥4 × LLOQ. Pre IMP dose 2 is also 3 weeks post dose 1 for Cohort 6.

Time frame:: 1 month after Dose 2 and 1 month after Dose 3
Reported as:: Number · Percentage of participants

Part B - Cohort 6 - Percentages With SRs to VOCs (B.1.1.7, B.1.617.2) and Reference Strain
Percentage of participants	Part B - Cohort 6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.6172)
1 month post IMP dose 2 - B.1.1.7	86.8 (82.2 to 90.5)
1 month post IMP dose 3 - B.1.1.7	83.6 (78.8 to 87.7)
1 month post IMP dose 2 - B.1.617.2	88.9 (84.7 to 92.4)
1 month post IMP dose 3 - B.1.617.2	87.1 (82.7 to 90.8)
1 month post IMP dose 2 - Reference strain	87.5 (83.0 to 91.1)
1 month post IMP dose 3 - Reference strain	89.5 (85.4 to 92.8)

SecondaryPart B - GMTs of VOC in COVID-19 Vaccine-naïve Participants With and Without Evidence of Prior Infection in Part B C6 (1 and 2 Primary Doses Respectively) and in BNT162b2-Experienced Participants Without Evidence of Infection in Part B C1 (1 Booster Dose)

GMTs of VOC specific NTs (B.1.1.7, B.1.617.2, B.1.1.529.5 \[Omicron BA.5\]) 3 weeks after one dose of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 vaccine-naïve participants with evidence of prior infection (Cohort 6), 1 month after two doses of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 vaccine-naïve participants without evidence of infection (Cohort 6), and 1 month after one booster dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced participants without evidence of infection (Cohort 1). GMTs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5 × LLOQ; assay results above the ULOQ were set to ULOQ.

Time frame:: Day 1 up to 1 month after 1 booster dose in Part B Cohort 1 without evidence of infection, up to 1 month after 2 doses in Part B Cohort 6 without evidence of infection and up to 3 weeks after 1 dose in Part B Cohort 6 with evidence of prior infection
Reported as:: Geometric mean · Titer

Part B - GMTs of VOC in COVID-19 Vaccine-naïve Participants With and Without Evidence of Prior Infection in Part B C6 (1 and 2 Primary Doses Respectively) and in BNT162b2-Experienced Participants Without Evidence of Infection in Part B C1 (1 Booster Dose)
Titer	Part B - Cohort 6: BNT162b2 With Evidence of Prior Infection	Part B - Cohort 6: BNT162b2 Without Evidence of Infection	Part B - Cohort 1: BNT162b2 Without Evidence of Infection
SARS-CoV-2 neutralization assay - B.1.1.7	1045.3 (853.1 to 1280.8)	180.8 (91.8 to 356.3)	749.5 (621.1 to 904.6)
SARS-CoV-2 neutralization assay - B.1.617.2	859.9 (693.4 to 1066.4)	62.6 (30.9 to 127.0)	466.6 (401.8 to 541.9)
SARS-CoV-2 neutralization assay - B.1.1.529.5	229.3 (191.7 to 274.4)	10.2 (5.7 to 18.3)	80.8 (66.9 to 97.6)

SecondaryPart B - GMRs of VOC in COVID-19 Vaccine-naïve Participants With and Without Evidence of Prior Infection (1 and 2 Primary Doses Respectively) and in BNT162b2-Experienced Participants Without Evidence of Infection (1 Booster Dose)

GMR of VOC specific NTs (B.1.1.7, B.1.617.2, B.1.1.529.5 \[Omicron BA.5\]) 3 weeks after one dose of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 vaccine-naïve participants with evidence of prior infection (Cohort 6) to the VOCs NTs 1 month after two doses of BNT162b2 (B.1.1.7 + B.1.617.2) in participants without evidence of infection (Cohort 6), and to the VOCs NTs 1 month after one booster dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced participants without evidence of infection (Cohort 1). GMRs and 2-sided 95% CIs were calculated by exponentiating the difference of the LS means and corresponding CIs based on the analysis of logarithmically transformed neutralizing titers using a linear regression model with terms of age, sex, and group. A separate model was fit for each comparison. Assay results below the LLOQ were set to 0.5 × LLOQ; assay results above the ULOQ were set to ULOQ.

Time frame:: Day 1 to Day 29
Reported as:: Geometric mean · Titer ratio

Part B - GMRs of VOC in COVID-19 Vaccine-naïve Participants With and Without Evidence of Prior Infection (1 and 2 Primary Doses Respectively) and in BNT162b2-Experienced Participants Without Evidence of Infection (1 Booster Dose)
Titer ratio	Part B - Cohort 6 With Prior Infection / Cohort 6 Without Prior Infection	Part B - Cohort 6 With Prior Infection / Cohort 1 Without Prior Infection
SARS-CoV-2 neutralization assay - B.1.1.7	7.66 (4.09 to 14.33)	1.46 (1.10 to 1.93)
SARS-CoV-2 neutralization assay - B.1.617.2	15.43 (7.87 to 30.28)	1.88 (1.44 to 2.45)
SARS-CoV-2 neutralization assay - B.1.1.529.5	29.86 (17.31 to 51.49)	2.94 (2.26 to 3.82)

SecondaryPart B - Difference in SRs to VOCs in COVID-19 Vaccine-naïve Participants With and Without Evidence of Prior Infection (1 and 2 Primary Doses Respectively) and in BNT162b2-Experienced Participants Without Evidence of Infection (1 Booster Dose)

The difference in SRs to VOC specific NTs (B.1.1.7, B.1.617.2, B.1.1.529.5 \[Omicron BA.5\]) 3 weeks after one dose of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 vaccine-naïve participants with evidence of prior infection (Cohort 6) to those 1 month after two doses of BNT162b2 (B.1.1.7 + B.1.617.2) in participants without evidence of infection (Cohort 6), and to those 1 month after one booster dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced participants without evidence of infection (Cohort 1). Adjusted difference in proportions estimated using minimum risk weights and stratified by sex and age group (18 to 55 years, 56 to 85 years), expressed as a percentage. 2-Sided CI based on the Newcombe method stratified by sex and age group (18 to 55 years, 56 to 85 years) with minimum risk weights for the difference in proportions.

Time frame:: Day 1 to Day 29
Reported as:: Number · Percentage difference

Part B - Difference in SRs to VOCs in COVID-19 Vaccine-naïve Participants With and Without Evidence of Prior Infection (1 and 2 Primary Doses Respectively) and in BNT162b2-Experienced Participants Without Evidence of Infection (1 Booster Dose)
Percentage difference	Part B - Cohort 6 With Prior Infection / Cohort 6 Without Prior Infection	Part B - Cohort 6 With Prior Infection / Cohort 1 Without Prior Infection
SARS-CoV-2 neutralization assay - B.1.1.7	6.95 (-9.69 to 32.17)	-9.75 (-16.43 to -3.24)
SARS-CoV-2 neutralization assay - B.1.617.2	20.90 (-0.62 to 46.52)	-6.56 (-13.03 to -0.37)
SARS-CoV-2 neutralization assay - B.1.1.529.5	81.47 (54.28 to 90.07)	6.67 (-2.06 to 15.42)

SecondaryPart B - SR of VOC in COVID-19 Vaccine-naïve Participants With and Without Evidence of Prior Infection (1 and 2 Primary Doses Respectively) and in BNT162b2-Experienced Participants Without Evidence of Infection (1 Booster Dose)

SRs of VOC specific NTs (B.1.1.7, B.1.617.2, B.1.1.529.5 \[Omicron BA.5\]) 3 weeks after one dose of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 vaccine-naïve participants with evidence of prior infection (Cohort 6) 1 month after two doses of BNT162b2 (B.1.1.7 + B.1.617.2) in participants without evidence of infection (Cohort 6), and 1 month after one booster dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced participants without evidence of infection (Cohort 1). Seroresponse was defined as achieving a ≥4-fold rise from baseline. If the baseline measurement was below the LLOQ, a postvaccination assay result ≥4 × LLOQ was considered a seroresponse.

Time frame:: 3 weeks after one dose in participants with evidence of prior infection (Cohort 6), 1 month after two doses in participants without evidence of infection (Cohort 6), and 1 month after one booster dose (Cohort 1)
Reported as:: Number · Percentage of participants

Part B - SR of VOC in COVID-19 Vaccine-naïve Participants With and Without Evidence of Prior Infection (1 and 2 Primary Doses Respectively) and in BNT162b2-Experienced Participants Without Evidence of Infection (1 Booster Dose)
Percentage of participants	Part B - Cohort 6: BNT162b2 With Evidence of Prior Infection	Part B - Cohort 6: BNT162b2 Without Evidence of Infection	Part B - Cohort 1: BNT162b2 Without Evidence of Infection
SARS-CoV-2 neutralization assay - B.1.1.7	87.3 (80.7 to 92.3)	76.5 (50.1 to 93.2)	97.1 (92.6 to 99.2)
SARS-CoV-2 neutralization assay - B.1.617.2	89.4 (83.2 to 94.0)	58.8 (32.9 to 81.6)	96.3 (91.6 to 98.8)
SARS-CoV-2 neutralization assay - B.1.1.529.5	87.3 (80.7 to 92.3)	11.8 (1.5 to 36.4)	80.1 (72.4 to 86.5)

SecondaryPart C - GMT - B.1.1.529.1 in RNA Based COVID-19 Vaccine-experienced Participants With History of SARS-CoV-2 Infection

VOC NT in RNA-based COVID-19 vaccine-experienced participants with history of SARS-CoV-2 infection at baseline and 7 days, 1 month, and 3 months after the trial start for Cohorts 7, 8, and 9, and 6 and 12 months after the trial start for Cohorts 7 and 8. GMTs and 2-sided 95% CIs are calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ are set to 0.5 × LLOQ and above the ULOQ are set to ULOQ. Number of subjects with valid and determinate assay results for the specified variant at the given dose/sampling time point. No vaccination was given to Cohort 9 participants within 3 months after Visit 1. The term "post IMP" does not apply for Cohort 9 since no IMP was given, but blood was collected at the same timepoints post randomization.

Time frame:: Day 1 to Day 360
Reported as:: Geometric mean · Titer

Part C - GMT - B.1.1.529.1 in RNA Based COVID-19 Vaccine-experienced Participants With History of SARS-CoV-2 Infection
Titer	Part C - Cohort 7: 1 Dose of 30 μg BNT162b2 (B.1.1.529.1)	Part C - Cohort 8: 1 Dose of 30 μg BNT162b2 (Original Vaccine)	Part C - Cohort 9: No Vaccination
Baseline	169.2 (124.4 to 230.2)	388.5 (262.0 to 575.9)	164.0 (96.1 to 280.0)
1-week post IMP Dose 1	751.7 (571.5 to 988.9)	768.9 (550.0 to 1074.9)	211.7 (122.5 to 365.9)
1-month post IMP Dose 1	748.8 (572.0 to 980.3)	801.5 (569.8 to 1127.4)	180.4 (106.7 to 305.0)
3-months post IMP Dose 1	590.3 (433.6 to 803.6)	571.5 (411.5 to 793.8)	143.3 (86.7 to 236.9)
6-months post IMP Dose 1	289.6 (210.7 to 397.9)	356.8 (266.9 to 476.8)	—
12-months post IMP Dose 1	197.0 (142.5 to 272.3)	180.5 (135.9 to 239.8)	—

Adverse events

Collected over AEs: From Dose 1 to 1 Month after each dose; SAEs: From Dose 1 up to end of study, i.e., up to 18 months.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Part A - Cohort 1: 1 Dose of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	0/21 (0%)	0/21 (0%)	2/21 (9.5%)
Part A - Cohort 2: 2 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	0/20 (0%)	1/20 (5%)	7/20 (35%)
Part A - Cohort 3: 1 Dose of 30 μg BNT162b2 (B.1.1.7)	0/20 (0%)	1/20 (5%)	4/20 (20%)
Part A - Cohort 4: 1 Dose of 30 μg BNT162b2 (B.1.617.2)	0/20 (0%)	0/20 (0%)	0/20 (0%)
Part A - Cohort 5: 1 Dose of 30 μg BNT162b2 (Original Vaccine)	0/42 (0%)	0/42 (0%)	27/42 (64.3%)
Part A - Cohort 6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	0/17 (0%)	0/17 (0%)	6/17 (35.3%)
Part B - Cohort 1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	1/349 (0.3%)	6/349 (1.7%)	26/349 (7.4%)
Part B - Cohort 4: 1 Dose 30 μg BNT162b2 (B.1.617.2)	0/352 (0%)	9/352 (2.6%)	0/352 (0%)
Part B - Cohort 6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	2/361 (0.6%)	13/361 (3.6%)	39/361 (10.8%)
Part C - Cohort 7: 1 Dose of 30 μg BNT162b2 (B.1.1.529)	0/72 (0%)	0/72 (0%)	4/72 (5.6%)
Part C - Cohort 8: 1 Dose of 30 μg BNT162b2 (Original Vaccine)	0/71 (0%)	5/71 (7%)	5/71 (7%)

Most frequent serious events

Showing 10 of 44

Most frequent serious events
Event	Part A - Cohort 1: 1 Dose of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - Cohort 2: 2 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - Cohort 3: 1 Dose of 30 μg BNT162b2 (B.1.1.7)	Part A - Cohort 4: 1 Dose of 30 μg BNT162b2 (B.1.617.2)	Part A - Cohort 5: 1 Dose of 30 μg BNT162b2 (Original Vaccine)	Part A - Cohort 6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part B - Cohort 1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part B - Cohort 4: 1 Dose 30 μg BNT162b2 (B.1.617.2)	Part B - Cohort 6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part C - Cohort 7: 1 Dose of 30 μg BNT162b2 (B.1.1.529)	Part C - Cohort 8: 1 Dose of 30 μg BNT162b2 (Original Vaccine)
Obstructive pancreatitisGastrointestinal disorders	0/21	0/20	1/20	0/20	0/42	0/17	0/349	0/352	0/361	0/72	0/71
Hepatitis acuteHepatobiliary disorders	0/21	1/20	0/20	0/20	0/42	0/17	0/349	0/352	0/361	0/72	0/71
CholelithiasisHepatobiliary disorders	0/21	0/20	0/20	0/20	0/42	0/17	0/349	0/352	0/361	0/72	1/71
Fibula fractureInjury, poisoning and procedural complications	0/21	0/20	0/20	0/20	0/42	0/17	0/349	0/352	0/361	0/72	1/71
Lower limb fractureInjury, poisoning and procedural complications	0/21	0/20	0/20	0/20	0/42	0/17	0/349	0/352	0/361	0/72	1/71
Tibia fractureInjury, poisoning and procedural complications	0/21	0/20	0/20	0/20	0/42	0/17	0/349	0/352	0/361	0/72	1/71
Breast cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)	0/21	0/20	0/20	0/20	0/42	0/17	0/349	0/352	0/361	0/72	1/71
Papillary thyroid cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)	0/21	0/20	0/20	0/20	0/42	0/17	0/349	0/352	0/361	0/72	1/71
EpilepsyNervous system disorders	0/21	0/20	0/20	0/20	0/42	0/17	0/349	0/352	0/361	0/72	1/71
SeizureNervous system disorders	0/21	0/20	0/20	0/20	0/42	0/17	0/349	0/352	0/361	0/72	1/71

Most frequent other events

Showing 10 of 15

Most frequent other events
Event	Part A - Cohort 1: 1 Dose of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - Cohort 2: 2 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - Cohort 3: 1 Dose of 30 μg BNT162b2 (B.1.1.7)	Part A - Cohort 4: 1 Dose of 30 μg BNT162b2 (B.1.617.2)	Part A - Cohort 5: 1 Dose of 30 μg BNT162b2 (Original Vaccine)	Part A - Cohort 6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part B - Cohort 1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part B - Cohort 4: 1 Dose 30 μg BNT162b2 (B.1.617.2)	Part B - Cohort 6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part C - Cohort 7: 1 Dose of 30 μg BNT162b2 (B.1.1.529)	Part C - Cohort 8: 1 Dose of 30 μg BNT162b2 (Original Vaccine)
Product administration errorInjury, poisoning and procedural complications	0/21	0/20	0/20	0/20	22/42	0/17	0/349	0/352	0/361	0/72	0/71
FatigueGeneral disorders	1/21	4/20	2/20	0/20	2/42	2/17	0/349	0/352	0/361	0/72	0/71
HeadacheNervous system disorders	1/21	1/20	1/20	0/20	1/42	3/17	0/349	0/352	0/361	0/72	4/71
CoughRespiratory, thoracic and mediastinal disorders	0/21	0/20	0/20	0/20	0/42	2/17	0/349	0/352	0/361	0/72	0/71
Nasal congestionRespiratory, thoracic and mediastinal disorders	0/21	0/20	0/20	0/20	0/42	2/17	0/349	0/352	0/361	0/72	0/71
COVID-19Infections and infestations	0/21	2/20	1/20	0/20	0/42	1/17	26/349	0/352	39/361	0/72	0/71
LymphadenopathyBlood and lymphatic system disorders	1/21	1/20	2/20	0/20	1/42	0/17	0/349	0/352	0/361	4/72	1/71
DiarrhoeaGastrointestinal disorders	0/21	2/20	0/20	0/20	1/42	1/17	0/349	0/352	0/361	0/72	0/71
NauseaGastrointestinal disorders	0/21	1/20	1/20	0/20	0/42	1/17	0/349	0/352	0/361	0/72	0/71
Upper respiratory tract infectionInfections and infestations	0/21	0/20	0/20	0/20	0/42	1/17	0/349	0/352	0/361	0/72	0/71

Baseline characteristics

Part A and B: Safety Set - All participants who received at least one dose in of IMP. 35 participants were randomized to Part C - Cohort 9. As per protocol, these participants did not receive treatment.

Age, Continuous
Age, Continuous(years)	Part A - Cohort 1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - Cohort 2: 2 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - Cohort 3: 1 Dose of 30 μg BNT162b2 (B.1.1.7)	Part A - Cohort 4: 1 Dose of 30 μg BNT162b2 (B.1.617.2)	Part A - Cohort 5: 1 Dose of 30 μg BNT162b2 (Original Vaccine)	Part A - Cohort 6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part B - Cohort 1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part B - Cohort 4: 1 Dose 30 μg BNT162b2 (B.1.617.2)	Part B - Cohort 6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part C - Cohort 7: 1 Dose of 30 μg BNT162b2 (B.1.1.529)	Part C - Cohort 8: 1 Dose of 30 μg BNT162b2 (Original Vaccine)	Part C - Cohort 9: No Vaccination	Total
Part A	35.4 ± 11.13	38.7 ± 9.79	36.0 ± 11.89	39.8 ± 8.53	47.5 ± 11.10	37.1 ± 11.21	—	—	—	—	—	—	40.4 ± 11.61
Part B	—	—	—	—	—	—	48.1 ± 14.68	50.5 ± 15.27	42.1 ± 15.91	—	—	—	46.9 ± 15.70
Part C	—	—	—	—	—	—	—	—	—	41.9 ± 12.14	43.5 ± 13.57	44.5 ± 11.15	43.0 ± 12.52

Age, Customized
Age, Customized(Participants)	Part A - Cohort 1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - Cohort 2: 2 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - Cohort 3: 1 Dose of 30 μg BNT162b2 (B.1.1.7)	Part A - Cohort 4: 1 Dose of 30 μg BNT162b2 (B.1.617.2)	Part A - Cohort 5: 1 Dose of 30 μg BNT162b2 (Original Vaccine)	Part A - Cohort 6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part B - Cohort 1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part B - Cohort 4: 1 Dose 30 μg BNT162b2 (B.1.617.2)	Part B - Cohort 6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part C - Cohort 7: 1 Dose of 30 μg BNT162b2 (B.1.1.529)	Part C - Cohort 8: 1 Dose of 30 μg BNT162b2 (Original Vaccine)	Part C - Cohort 9: No Vaccination	Total
18 to 55 years old	21	20	20	20	42	17	222	210	242	61	60	31	966
56 to 85 years old	0	0	0	0	0	0	127	142	119	11	11	4	414

Sex: Female, Male
Sex: Female, Male(Participants)	Part A - Cohort 1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - Cohort 2: 2 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - Cohort 3: 1 Dose of 30 μg BNT162b2 (B.1.1.7)	Part A - Cohort 4: 1 Dose of 30 μg BNT162b2 (B.1.617.2)	Part A - Cohort 5: 1 Dose of 30 μg BNT162b2 (Original Vaccine)	Part A - Cohort 6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part B - Cohort 1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part B - Cohort 4: 1 Dose 30 μg BNT162b2 (B.1.617.2)	Part B - Cohort 6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part C - Cohort 7: 1 Dose of 30 μg BNT162b2 (B.1.1.529)	Part C - Cohort 8: 1 Dose of 30 μg BNT162b2 (Original Vaccine)	Part C - Cohort 9: No Vaccination	Total
Female	11	12	10	13	14	11	169	161	204	42	43	25	715
Male	10	8	10	7	28	6	180	191	157	30	28	10	665

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	Part A - Cohort 1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - Cohort 2: 2 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - Cohort 3: 1 Dose of 30 μg BNT162b2 (B.1.1.7)	Part A - Cohort 4: 1 Dose of 30 μg BNT162b2 (B.1.617.2)	Part A - Cohort 5: 1 Dose of 30 μg BNT162b2 (Original Vaccine)	Part A - Cohort 6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part B - Cohort 1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part B - Cohort 4: 1 Dose 30 μg BNT162b2 (B.1.617.2)	Part B - Cohort 6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part C - Cohort 7: 1 Dose of 30 μg BNT162b2 (B.1.1.529)	Part C - Cohort 8: 1 Dose of 30 μg BNT162b2 (Original Vaccine)	Part C - Cohort 9: No Vaccination	Total
American Indian or Alaska Native	0	0	0	0	0	0	1	2	0	0	0	1	4
Asian	0	1	1	1	4	0	10	6	0	4	4	1	32
Native Hawaiian or Other Pacific Islander	1	1	0	0	0	0	0	0	0	0	0	0	2
Black or African American	0	0	0	0	3	6	50	8	242	4	7	2	322
White	20	18	19	19	35	11	258	330	15	62	59	31	877
Other	0	0	0	0	0	0	0	3	63	0	0	0	66
Multiracial	0	0	0	0	0	0	30	3	41	0	1	0	75
Not reported	0	0	0	0	0	0	0	0	0	1	0	0	1
Unknown	0	0	0	0	0	0	0	0	0	1	0	0	1
Hispanic or Latino	7	3	9	1	5	5	30	55	10	12	5	5	147
Not Hispanic or Latino	14	17	11	19	37	12	317	294	348	59	66	30	1224
Unknown or Not Reported	0	0	0	0	0	0	2	3	3	1	0	0	9

Region of Enrollment
Region of Enrollment(participants)	Part A - Cohort 1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - Cohort 2: 2 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - Cohort 3: 1 Dose of 30 μg BNT162b2 (B.1.1.7)	Part A - Cohort 4: 1 Dose of 30 μg BNT162b2 (B.1.617.2)	Part A - Cohort 5: 1 Dose of 30 μg BNT162b2 (Original Vaccine)	Part A - Cohort 6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part B - Cohort 1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part B - Cohort 4: 1 Dose 30 μg BNT162b2 (B.1.617.2)	Part B - Cohort 6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part C - Cohort 7: 1 Dose of 30 μg BNT162b2 (B.1.1.529)	Part C - Cohort 8: 1 Dose of 30 μg BNT162b2 (Original Vaccine)	Part C - Cohort 9: No Vaccination	Total
Turkey	0	0	0	0	0	0	137	0	0	0	0	0	137
United States	21	20	20	20	42	17	134	284	23	62	62	32	737
South Africa	0	0	0	0	0	0	78	4	338	0	0	0	420
Germany	0	0	0	0	0	0	0	64	0	10	9	3	86

Body Mass Index (BMI)
Body Mass Index (BMI)(kg/m^2)	Part A - Cohort 1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - Cohort 2: 2 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - Cohort 3: 1 Dose of 30 μg BNT162b2 (B.1.1.7)	Part A - Cohort 4: 1 Dose of 30 μg BNT162b2 (B.1.617.2)	Part A - Cohort 5: 1 Dose of 30 μg BNT162b2 (Original Vaccine)	Part A - Cohort 6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part B - Cohort 1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part B - Cohort 4: 1 Dose 30 μg BNT162b2 (B.1.617.2)	Part B - Cohort 6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part C - Cohort 7: 1 Dose of 30 μg BNT162b2 (B.1.1.529)	Part C - Cohort 8: 1 Dose of 30 μg BNT162b2 (Original Vaccine)	Part C - Cohort 9: No Vaccination	Total
Part A	27.54 ± 5.508	27.97 ± 6.840	30.09 ± 6.509	29.72 ± 6.287	29.83 ± 6.722	30.82 ± 8.394	—	—	—	—	—	—	29.35 ± 6.663
Part B	—	—	—	—	—	—	28.29 ± 6.012	28.78 ± 6.202	26.30 ± 8.413	—	—	—	27.77 ± 7.065
Part C	—	—	—	—	—	—	—	—	—	29.25 ± 6.648	28.60 ± 6.581	30.23 ± 5.133	29.18 ± 6.346

Study locations

35 sites

Collaborative Neuroscience Network LLC
Long Beach, California 90806, United States
California Research Foundation
San Diego, California 92123, United States
Clinical Research Consulting, Llc
Milford, Connecticut 06460, United States
Stamford Therapeutics Consortium
Stamford, Connecticut 06905, United States
Atlanta Center for Medical Research
Atlanta, Georgia 30331, United States
Meridian Clinical Research
Savannah, Georgia 31406, United States
Medpharmics, LLC
Gulfport, Mississippi 39503, United States
Amici Clinical Research
Warren, New Jersey 07059, United States
Rochester Clinical Research
Rochester, New York 14609, United States
Aventiv Research Inc.
Columbus, Ohio 43213, United States
ARC Clinical Research
Austin, Texas 78745, United States
North Texas Infectious Diseases Consultants
Dallas, Texas 75246, United States
Clinical Trials of Texas Inc.
San Antonio, Texas 78229, United States
Diagnostics Research Group
San Antonio, Texas 78229, United States
CRS Clinical Research Services Berlin
Berlin, 13353, Germany
IKF Institut fuer klinische Forschung Frankfurt
Frankfurt am Main, 60596, Germany
CRS Clinical Research Services Mannheim GmbH
Mannheim, 68167, Germany
Studienzentrum Brinkum Dr. Lars Pohlmeier und Torsten Drescher
Stuhr, 28816, Germany
JOSHA Research
Bloemfontein, Free State 09301, South Africa
Langeberg Medicross Medical Centre
Kraaifontein, Western Cape 75070, South Africa
Paarl Research Centre
Paarl, Western Cape 07646, South Africa
Synexus Helderberg Clinical Trial Centre
Somerset West, Western Cape 07130, South Africa
Worthwhile Clinical Trials
Benoni, 01501, South Africa
Tiervlei Trial Centre
Cape Town, 07530, South Africa
Midrand Medical Centre
Halfway House, 01685, South Africa
Newtown Clinical Research
Johannesburg, 02113, South Africa
Global Clinical Trials
Pretoria, 00001, South Africa
Botho ke Bontle Health Service
Pretoria, 00122, South Africa
Synexus SA Stanza Clinical Research Centre
Pretoria, 00122, South Africa
Jongaie Research, Medicross Pretoria West
Pretoria, 00183, South Africa
Ankara University Faculty of Medicine, Avicenna Hospital
Ankara, 06100, Turkey
Hacettepe University Hospital
Ankara, 06100, Turkey
Bagcilar Medipol Mega University Hospital
Istanbul, 34214, Turkey
Istanbul University Medical Faculty
Istanbul, 34390, Turkey
Kocaeli Universitesi Tip Fakultesi
Kocaeli, 41380, Turkey

References and documents

Study documents

Study protocol · Jun 28, 2023
Statistical analysis plan · Feb 23, 2024

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Nov 22, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT05004181
Lead sponsor: BioNTech SE
Responsible party: Sponsor
First posted: Aug 13, 2021
Start date: Aug 25, 2021
Primary completion: Aug 16, 2023
Completion: Oct 4, 2023
Results posted: Nov 22, 2024
Last update: Nov 22, 2024

Study contacts

BioNTech Responsible Person

study director · BioNTech SE

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

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