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

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)

Population: Safety set, i.e., all participants who received at least one dose of IMP. Per protocol, participants in Part C - Cohort 9 did not receive IMP therefore local reactions were not collected for these participants.

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

Population: Reactogenicity set, i.e., all participants included in the Safety Set with any reactogenicity data reported after IMP injection. Per protocol, participants in Part C - Cohort 9 did not receive IMP therefore local reactions were not collected for these participants.

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

Population: Safety set, i.e., all participants who received at least one dose of IMP. Per protocol, participants in Part C - Cohort 9 did not receive IMP therefore local reactions were not collected for these participants.

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

Population: Reactogenicity set, i.e., all subjects included in the Safety Set with any reactogenicity data reported after IMP injection. Per protocol, participants in Part C - Cohort 9 did not receive IMP therefore local reactions were not collected for these participants.

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

Population: Immunogenicity Analysis Set, i.e., all eligible randomized/assigned participants who received the trial intervention to which they were randomized or assigned, had a valid and determinate immunogenicity result from the blood sample collected within an appropriate window, and had no other important protocol deviations that could confound immunogenicity data. Includes 332 subjects 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

Population: Immunogenicity Analysis Set, i.e., all eligible randomized/assigned participants who received the trial intervention to which they were randomized or assigned, had a valid and determinate immunogenicity result from the blood sample collected within an appropriate window, and had no other important protocol deviations that could confound immunogenicity data. Includes 332 subjects 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

Population: Immunogenicity Analysis Set, i.e., all eligible randomized/assigned participants who received the trial intervention to which they were randomized or assigned, had a valid and determinate immunogenicity result from the blood sample collected within an appropriate window, and had no other important protocol deviations that could confound immunogenicity data. Includes 320 subjects from C4591001 (NCT04368728).

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

Population: Immunogenicity Analysis Set, i.e., all eligible randomized/assigned participants who received the trial intervention to which they were randomized or assigned, had a valid and determinate immunogenicity result from the blood sample collected within an appropriate window, and had no other important protocol deviations that could confound immunogenicity data. Includes 332 subjects from C4591001 (NCT04368728).

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

Population: The population recruited in Cohort B6 were retrospectively seropositive for SARS-CoV-2. While the cohort was COVID-19 vaccine-naïve, it was not SARS-CoV-2-naïve as needed to match the control group (C4591001/NCT04368728). Control participants were therefore not selected as planned so data were not available to calculate the GMR. GMT data for the 17 participants without evidence of infection are presented in Outcome Measure 28. Please refer to the outcome measure description for more detail.

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

Population: Immunogenicity Analysis Set, i.e., all eligible randomized/assigned participants who received the trial intervention to which they were randomized or assigned, had a valid and determinate immunogenicity result from the blood sample collected within an appropriate window, and had no other important protocol deviations that could confound immunogenicity data. Includes 332 subjects from C4591001 (NCT04368728).

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

Population: Immunogenicity Analysis Set, i.e., all eligible randomized/assigned participants who received the trial intervention to which they were randomized or assigned, had a valid and determinate immunogenicity result from the blood sample collected within an appropriate window, and had no other important protocol deviations that could confound immunogenicity data. Includes 320 subjects from C4591001 (NCT04368728).

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

Population: The population recruited in Cohort B6 were retrospectively seropositive for SARS-CoV-2. While the cohort was COVID-19 vaccine-naïve, it was not SARS-CoV-2-naïve as needed to match the control group (C4591001/NCT04368728). Control participants were therefore not selected as planned so data were not available to calculate the GMR. GMT data for the 17 participants without evidence of infection are presented in Outcome Measure 28. Please refer to the outcome measure description for more detail.

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

Population: Immunogenicity Analysis Set, i.e., all eligible randomized/assigned participants who received the trial intervention to which they were randomized or assigned, had a valid and determinate immunogenicity result from the blood sample collected within an appropriate window, and had no other important protocol deviations that could confound immunogenicity data. Includes 275 participants from C4591001 (NCT04368728).

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

Population: Immunogenicity Analysis Set, i.e., all eligible randomized/assigned participants who received the trial intervention to which they were randomized or assigned, had a valid and determinate immunogenicity result from the blood sample collected within an appropriate window, and had no other important protocol deviations that could confound immunogenicity data. Includes 275 participants from C4591001 (NCT04368728).

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

Population: The population recruited in Cohort B6 were retrospectively seropositive for SARS-CoV-2. While the cohort was COVID-19 vaccine-naïve, it was not SARS-CoV-2-naïve as needed to match the control group (C4591001/NCT04368728). Control participants were therefore not selected as planned so data were not available to calculate difference in SR. SR data for 17 participants without evidence of infection are presented in Outcome Measure 31. Please refer to the outcome measure description for more detail.

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

Population: The population recruited in Cohort B6 were retrospectively seropositive for SARS-CoV-2. While the cohort was COVID-19 vaccine-naïve, it was not SARS-CoV-2-naïve as needed to match the control group (C4591001/NCT04368728). Control participants were therefore not selected as planned so data were not available to calculate difference in SR. SR data for 17 participants without evidence of infection are presented in Outcome Measure 31. Please refer to the outcome measure description for more detail.

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)

Population: Immunogenicity Analysis Set, i.e., all eligible randomized/assigned participants who received the trial intervention to which they were randomized or assigned, had a valid and determinate immunogenicity result from the blood sample collected within an appropriate window, and had no other important protocol deviations that could confound immunogenicity data.

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)

Population: Immunogenicity Analysis Set, i.e., all eligible randomized/assigned participants who received the trial intervention to which they were randomized or assigned, had a valid and determinate immunogenicity result from the blood sample collected within an appropriate window, and had no other important protocol deviations that could confound immunogenicity data.

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

Population: Immunogenicity Analysis Set, i.e., all eligible randomized/assigned participants who received the trial intervention to which they were randomized or assigned, had a valid and determinate immunogenicity result from the blood sample collected within an appropriate window, and had no other important protocol deviations that could confound immunogenicity data.

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

Population: Immunogenicity Analysis Set, i.e., all eligible randomized/assigned participants who received the trial intervention to which they were randomized or assigned, had a valid and determinate immunogenicity result from the blood sample collected within an appropriate window, and had no other important protocol deviations that could confound immunogenicity data.

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

Population: Immunogenicity Analysis Set, i.e., all eligible randomized/assigned participants who received the trial intervention to which they were randomized or assigned, had a valid and determinate immunogenicity result from the blood sample collected within an appropriate window, and had no other important protocol deviations that could confound immunogenicity data.

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

Population: Immunogenicity Analysis Set, i.e., all eligible randomized/assigned participants who received the trial intervention to which they were randomized or assigned, had a valid and determinate immunogenicity result from the blood sample collected within an appropriate window, and had no other important protocol deviations that could confound immunogenicity data.

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

Population: Immunogenicity Analysis Set, i.e., all eligible randomized/assigned participants who received the trial intervention to which they were randomized or assigned, had a valid and determinate immunogenicity result from the blood sample collected within an appropriate window, and had no other important protocol deviations that could confound immunogenicity data.

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

Population: Immunogenicity Analysis Set, i.e., all eligible randomized/assigned participants who received the trial intervention to which they were randomized or assigned, had a valid and determinate immunogenicity result from the blood sample collected within an appropriate window, and had no other important protocol deviations that could confound immunogenicity data.

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

Population: Immunogenicity Analysis Set, i.e., all eligible randomized/assigned participants who received the trial intervention to which they were randomized or assigned, had a valid and determinate immunogenicity result from the blood sample collected within an appropriate window, and had no other important protocol deviations that could confound immunogenicity data.

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

Population: Immunogenicity Analysis Set Immunogenicity Analysis Set, i.e., all eligible randomized/assigned participants who received the trial intervention to which they were randomized or assigned, had a valid and determinate immunogenicity result from the blood sample collected within an appropriate window, and had no other important protocol deviations that could confound immunogenicity data. Includes 332 subjects from C4591001 (NCT04368728).

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

Population: Immunogenicity Analysis Set, i.e., all eligible randomized/assigned participants who received the trial intervention to which they were randomized or assigned, had a valid and determinate immunogenicity result from the blood sample collected within an appropriate window, and had no other important protocol deviations that could confound immunogenicity data. Includes 320 subjects from C4591001 (NCT04368728).

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

Population: Immunogenicity Analysis Set

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

Population: Immunogenicity Analysis Set, i.e., all eligible randomized/assigned participants who received the trial intervention to which they were randomized or assigned, had a valid and determinate immunogenicity result from the blood sample collected within an appropriate window, and had no other important protocol deviations that could confound immunogenicity data. Includes 332 subjects from C4591001 (NCT04368728).

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

Population: Immunogenicity Analysis Set, i.e., all eligible randomized/assigned participants who received the trial intervention to which they were randomized or assigned, had a valid and determinate immunogenicity result from the blood sample collected within an appropriate window, and had no other important protocol deviations that could confound immunogenicity data. Includes 320 subjects from C4591001 (NCT04368728).

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)

Population: Immunogenicity Analysis Set, i.e., all eligible randomized/assigned participants who received the trial intervention to which they were randomized or assigned, had a valid and determinate immunogenicity result from the blood sample collected within an appropriate window, and had no other important protocol deviations that could confound immunogenicity data.

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

Population: Immunogenicity Analysis Set, i.e., all eligible randomized/assigned participants who received the trial intervention to which they were randomized or assigned, had a valid and determinate immunogenicity result from the blood sample collected within an appropriate window, and had no other important protocol deviations that could confound immunogenicity data.