A Phase 3 Study to Evaluate the Safety, Tolerability, and Immunogenicity of Multiple Production Lots and Dose Levels of BNT162b2 RNA-Based COVID-19 Vaccines Against COVID-19 in Healthy Participants

GMCs were calculated by exponentiating the mean logarithm of the concentrations and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5\*LLOQ.

Time frame: 1 Month after Dose 2 of primary study

Population: Booster evaluable immunogenicity population: Participants who received 2 doses of vaccine in primary study, Dose 2 - primary study, Dose 3 - booster study within predefined window, had at least 1 valid immunogenicity result from blood sample collected within appropriate window at 1 month after Dose 3, were negative for both SARS-CoV-2 test at Dose 1,1-month post Dose 2, 3, and had no other protocol deviations determined by clinician. Here, N = participants evaluable for this outcome measure.

GMCs were calculated by exponentiating the mean logarithm of the concentrations and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5\*LLOQ.

Time frame: 1 Month after Dose 3

Population: Booster evaluable immunogenicity population: Participants who received 2 doses of vaccine in primary study, Dose 2 - primary study, Dose 3 - booster study within predefined window, had at least 1 valid immunogenicity result from blood sample collected within appropriate window at 1 month after Dose 3, were negative for both SARS-CoV-2 test at Dose 1,1-month post Dose 2, 3, and had no other protocol deviations determined by clinician. Here, N = participants evaluable for this outcome measure.

GMCs were calculated by exponentiating the mean logarithm of the concentrations and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5\*LLOQ.

Time frame: 1 Week after Dose 3

Population: Booster evaluable immunogenicity population: Participants who received 2 doses of vaccine in primary study, Dose 2 - primary study, Dose 3 - booster study within predefined window, had at least 1 valid immunogenicity result from blood sample collected within appropriate window at 1 month after Dose 3, were negative for both SARS-CoV-2 test at Dose 1,1-month post Dose 2, 3, and had no other protocol deviations determined by clinician. Here, N = participants evaluable for this outcome measure.

GMCs were calculated by exponentiating the mean logarithm of the concentrations and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5\*LLOQ.

Time frame: Baseline (prior to Dose 1 of Primary study)

Population: Booster evaluable immunogenicity population: Participants who received 2 doses of vaccine in primary study, Dose 2 - primary study, Dose 3 - booster study within predefined window, had at least 1 valid immunogenicity result from blood sample collected within appropriate window at 1 month after Dose 3, were negative for both SARS-CoV-2 test at Dose 1,1-month post Dose 2, 3, and had no other protocol deviations determined by clinician. Here, N = participants evaluable for this outcome measure.

GMCs were calculated by exponentiating the mean logarithm of the concentrations and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5\*LLOQ.

Time frame: Before Dose 3

Population: Booster evaluable immunogenicity population: Participants who received 2 doses of vaccine in primary study, Dose 2 - primary study, Dose 3 - booster study within predefined window, had at least 1 valid immunogenicity result from blood sample collected within appropriate window at 1 month after Dose 3, were negative for both SARS-CoV-2 test at Dose 1,1-month post Dose 2, 3, and had no other protocol deviations determined by clinician. Here, N = participants evaluable for this outcome measure.

GMFRs were defined as ratios of the geometric mean titers of SARS-CoV-2 B.1.351-strain at 1 month after Dose 3 to the geometric mean titers of SARS-CoV-2 B.1.351-strain before dose 3. GMFRs were calculated by exponentiating the mean logarithm of fold rises and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5\*LLOQ.

Time frame: Before Dose 3 to 1 Month after Dose 3

Population: Booster evaluable immunogenicity population: Participants who received 2 doses of vaccine in primary study, Dose 2 - primary study, Dose 3 - booster study within predefined window, had at least 1 valid immunogenicity result from blood sample collected within appropriate window at 1 month after Dose 3, were negative for both SARS-CoV-2 test at Dose 1,1-month post Dose 2, 3, and had no other protocol deviations determined by clinician. Here, N = participants evaluable for this outcome measure.

GMFRs were defined as ratios of the geometric mean titers of SARS-CoV-2 B.1.351-strain at 1 week after Dose 3 to the geometric mean titers of SARS-CoV-2 B.1.351-strain before dose 3. GMFRs were calculated by exponentiating the mean logarithm of fold rises and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5\*LLOQ.

Time frame: Before Dose 3 to 1 Week after Dose 3

Population: Booster evaluable immunogenicity population: Participants who received 2 doses of vaccine in primary study, Dose 2 - primary study, Dose 3 - booster study within predefined window, had at least 1 valid immunogenicity result from blood sample collected within appropriate window at 1 month after Dose 3, were negative for both SARS-CoV-2 test at Dose 1,1-month post Dose 2, 3, and had no other protocol deviations determined by clinician. Here, N = participants evaluable for this outcome measure.

GMFRs were defined as ratios of the geometric mean titers of SARS-CoV-2 B.1.351-strain at 1 month after Dose 3 to the geometric mean titers of SARS-CoV-2 B.1.351-strain at 1 month after dose 2. GMFRs were planned to be calculated by exponentiating the mean logarithm of fold rises and the corresponding CIs (based on the Student t distribution).

Time frame: From 1 Month after Dose 2 to 1 Month after Dose 3

Population: Data for this outcome was not analyzed as the immunogenicity samples were not tested for SARS-CoV-2 B.1.351-strain at 1 month after dose 2 as the South African strain was no longer of clinical interest and required responses have been well understood from other studies.

GMFRs were defined as ratios of the geometric mean titers of SARS-CoV-2 B.1.351-strain at 1 week after Dose 3 to the geometric mean titers of SARS-CoV-2 B.1.351-strain at 1 month after dose 2. GMFRs were planned to be calculated by exponentiating the mean logarithm of fold rises and the corresponding CIs (based on the Student t distribution).

Time frame: From 1 Month after Dose 2 to 1 Week after Dose 3

Population: Data for this outcome was not analyzed as the immunogenicity samples from 1 month after dose 2 were not tested for SARS-CoV-2 B.1.351-strain as the South African strain was no longer of clinical interest and required responses have been well understood from other studies.

GMFRs were defined as ratios of the geometric mean titers of SARS-CoV-2 reference-strain at 1 month after Dose 3 to the geometric mean titers of SARS-CoV-2 reference-strain before dose 3. GMFRs were calculated by exponentiating the mean logarithm of fold rises and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5\*LLOQ.

Time frame: Before Dose 3 to 1 Month after Dose 3

Population: Booster evaluable immunogenicity population: Participants who received 2 doses of vaccine in primary study, Dose 2 - primary study, Dose 3 - booster study within predefined window, had at least 1 valid immunogenicity result from blood sample collected within appropriate window at 1 month after Dose 3, were negative for both SARS-CoV-2 test at Dose 1,1-month post Dose 2, 3, and had no other protocol deviations determined by clinician. Here, N = participants evaluable for this outcome measure.

GMFRs were defined as ratios of the geometric mean titers of SARS-CoV-2 reference-strain at 1 week after Dose 3 to the geometric mean titers of SARS-CoV-2 reference-strain before dose 3. GMFRs were calculated by exponentiating the mean logarithm of fold rises and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5\*LLOQ.

Time frame: Before Dose 3 to 1 Week after Dose 3

Population: Booster evaluable immunogenicity population: Participants who received 2 doses of vaccine in primary study, Dose 2 - primary study, Dose 3 - booster study within predefined window, had at least 1 valid immunogenicity result from blood sample collected within appropriate window at 1 month after Dose 3, were negative for both SARS-CoV-2 test at Dose 1,1-month post Dose 2, 3, and had no other protocol deviations determined by clinician. Here, N = participants evaluable for this outcome measure.

GMFRs were defined as ratios of the geometric mean titers of SARS-CoV-2 reference-strain at 1 month after Dose 3 to the geometric mean titers of SARS-CoV-2 reference-strain at 1 month after dose 2. GMFRs were calculated by exponentiating the mean logarithm of fold rises and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5\*LLOQ.

Time frame: From 1 Month after Dose 2 to 1 Month after Dose 3

Population: Booster evaluable immunogenicity population: Participants who received 2 doses of vaccine in primary study, Dose 2 - primary study, Dose 3 - booster study within predefined window, had at least 1 valid immunogenicity result from blood sample collected within appropriate window at 1 month after Dose 3, were negative for both SARS-CoV-2 test at Dose 1,1-month post Dose 2, 3, and had no other protocol deviations determined by clinician. Here, N = participants evaluable for this outcome measure.

GMFRs were defined as ratios of the geometric mean titers of SARS-CoV-2 reference-strain at 1 week after Dose 3 to the geometric mean titers of SARS-CoV-2 reference-strain at 1 month after dose 2. GMFRs were calculated by exponentiating the mean logarithm of fold rises and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5\*LLOQ.

Time frame: From 1 Month after Dose 2 to 1 Week after Dose 3

Population: Booster evaluable immunogenicity population: Participants who received 2 doses of vaccine in primary study, Dose 2 - primary study, Dose 3 - booster study within predefined window, had at least 1 valid immunogenicity result from blood sample collected within appropriate window at 1 month after Dose 3, were negative for both SARS-CoV-2 test at Dose 1,1-month post Dose 2, 3, and had no other protocol deviations determined by clinician. Here, N = participants evaluable for this outcome measure.

GMFRs were defined as ratios of the geometric mean concentration of IgG at 1 month after Dose 3 to the geometric mean concentration of IgG before dose 3. GMFRs were calculated by exponentiating the mean logarithm of fold rises and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5\*LLOQ.

Time frame: Before Dose 3 to 1 Month after Dose 3

Population: Booster evaluable immunogenicity population: Participants who received 2 doses of vaccine in primary study, Dose 2 - primary study, Dose 3 - booster study within predefined window, had at least 1 valid immunogenicity result from blood sample collected within appropriate window at 1 month after Dose 3, were negative for both SARS-CoV-2 test at Dose 1,1-month post Dose 2, 3, and had no other protocol deviations determined by clinician. Here, N = participants evaluable for this outcome measure.

GMFRs were defined as ratios of the geometric mean concentration of IgG at 1 week after Dose 3 to the geometric mean concentration of IgG before dose 3. GMFRs were calculated by exponentiating the mean logarithm of fold rises and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5\*LLOQ.

Time frame: Before Dose 3 to 1 Week after Dose 3

Population: Booster evaluable immunogenicity population: Participants who received 2 doses of vaccine in primary study, Dose 2 - primary study, Dose 3 - booster study within predefined window, had at least 1 valid immunogenicity result from blood sample collected within appropriate window at 1 month after Dose 3, were negative for both SARS-CoV-2 test at Dose 1,1-month post Dose 2, 3, and had no other protocol deviations determined by clinician. Here, N = participants evaluable for this outcome measure.

GMFRs were defined as ratios of the geometric mean concentration of IgG at 1 month after Dose 3 to the geometric mean concentration of IgG at 1 month after dose 2. GMFRs were calculated by exponentiating the mean logarithm of fold rises and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5\*LLOQ.

Time frame: From 1 Month after Dose 2 to 1 Month after Dose 3

Population: Booster evaluable immunogenicity population: Participants who received 2 doses of vaccine in primary study, Dose 2 - primary study, Dose 3 - booster study within predefined window, had at least 1 valid immunogenicity result from blood sample collected within appropriate window at 1 month after Dose 3, were negative for both SARS-CoV-2 test at Dose 1,1-month post Dose 2, 3, and had no other protocol deviations determined by clinician. Here, N = participants evaluable for this outcome measure.

GMFRs were defined as ratios of the geometric mean concentration of IgG at 1 week after Dose 3 to the geometric mean concentration of IgG at 1 month after dose 2. GMFRs were calculated by exponentiating the mean logarithm of fold rises and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5\*LLOQ.

Time frame: From 1 Month after Dose 2 to 1 Week after Dose 3

Population: Booster evaluable immunogenicity population: Participants who received 2 doses of vaccine in primary study, Dose 2 - primary study, Dose 3 - booster study within predefined window, had at least 1 valid immunogenicity result from blood sample collected within appropriate window at 1 month after Dose 3, were negative for both SARS-CoV-2 test at Dose 1,1-month post Dose 2, 3, and had no other protocol deviations determined by clinician. Here, N = participants evaluable for this outcome measure.

Geometric mean concentration of full-length S-binding IgG level for EU lot and pooled US lots (BNT162b2 30 mcg: US Lot 1, BNT162b2 30 mcg: US Lot 2 and BNT162b2 30 mcg: US Lot 3 reporting arm) were determined and reported in the descriptive section. Assay results below the LLOQ were set to 0.5\*LLOQ. GMRs were reported in the statistical analysis section and was calculated as ratios of GMCs of BNT162b2 30 mcg: EU Lot and pooled US Lots (BNT162b2 30 mcg: US Lot 1, BNT162b2 30 mcg: US Lot 2 and BNT162b2 30 mcg: US Lot 3 reporting arm).

Time frame: 1 Month after Dose 2

Population: Evaluable immunogenicity population: Participants who received 2 doses of vaccine in primary study, with Dose 2 received within predefined window, had at least 1 valid immunogenicity result from blood sample collected within an appropriate window at 1 month after Dose 2, were negative for both SARS-CoV-2 test (RT-PCR and N-blinding antibody) during study and had no other protocol deviations determined by clinician. Here, N= participants evaluable for this outcome measure.

Geometric mean concentration of full-length S-binding IgG level for individual US lots (US lots 1, 2, and 3) was determined and reported in the descriptive section. Assay results below the lower limit of quantitation (LLOQ) were set to 0.5\*LLOQ. GMRs were reported in the statistical analysis section and was calculated as ratio of Geometric Mean Concentrations (GMCs) of individual US Lots BNT162b2 30 mcg: US Lot 1, BNT162b2 30 mcg: US Lot 2 and BNT162b2 30 mcg: US Lot 3.

Time frame: 1 Month after Dose 2

Population: Evaluable immunogenicity population: Participants who received 2 doses of vaccine in primary study, with Dose 2 received within predefined window, had at least 1 valid immunogenicity result from blood sample collected within an appropriate window at 1 month after Dose 2, were negative for both SARS-CoV-2 test (RT-PCR and N-blinding antibody) during study and had no other protocol deviations determined by clinician. Here, N= participants evaluable for this outcome measure.

Geometric mean titer for SARS-CoV-2 neutralizing titers for 20 mcg dose and 30 mcg dose of US Lot 1 was determined and reported in the descriptive section. GMTs and 2-sided 95% CIs were calculated by exponentiating the least square (LS) mean of the titers and corresponding CIs based on linear regression model. Assay results below the LLOQ were set to 0.5\*LLOQ. GMRs were reported in the statistical analysis section and were calculated as the ratio of geometric mean titer of the 20-mcg dose (US Lot 1) to the geometric mean titer of the 30 mcg dose (US Lot 1).

Time frame: 1 Month after Dose 2

Population: Evaluable immunogenicity population: Participants who received 2 doses of vaccine in primary study, with Dose 2 received within predefined window, had at least 1 valid immunogenicity result from blood sample collected within an appropriate window at 1 month after Dose 2, were negative for both SARS-CoV-2 test (RT-PCR and N-blinding antibody) during study and had no other protocol deviations determined by clinician. Here, N= participants evaluable for this outcome measure.

GMTs and 2-sided 95% CIs were planned to be calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on the Student t distribution).

Time frame: 1 Month after Dose 2 of primary study

Population: Data for this outcome was not analyzed as the immunogenicity samples were not tested for SARS-CoV-2 B.1.351-strain at 1 month after dose 2 as the South African strain was no longer of clinical interest and required responses have been well understood from other studies.

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.

Time frame: 1 Month after Dose 3

Population: Booster evaluable immunogenicity population: Participants who received 2 doses of vaccine in primary study, Dose 2 - primary study, Dose 3 - booster study within predefined window, had at least 1 valid immunogenicity result from blood sample collected within appropriate window at 1 month after Dose 3, were negative for both SARS-CoV-2 test at Dose 1,1-month post Dose 2, 3, and had no other protocol deviations determined by clinician. Here, N = participants evaluable for this outcome measure.

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.

Time frame: 1 Week after Dose 3

Population: Booster evaluable immunogenicity population: Participants who received 2 doses of vaccine in primary study, Dose 2 - primary study, Dose 3 - booster study within predefined window, had at least 1 valid immunogenicity result from blood sample collected within appropriate window at 1 month after Dose 3, were negative for both SARS-CoV-2 test at Dose 1,1-month post Dose 2, 3, and had no other protocol deviations determined by clinician. Here, N = participants evaluable for this outcome measure.

GMTs and 2-sided 95% CIs were planned to be calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on the Student t distribution).

Time frame: Baseline (prior to Dose 1 of Primary study)

Population: Data for this outcome was not analyzed as the immunogenicity samples were not tested for SARS-CoV-2 B.1.351-strain at Baseline as the South African strain was no longer of clinical interest and required responses have been well understood from other studies.

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.

Time frame: Before Dose 3

Population: Booster evaluable immunogenicity population: Participants who received 2 doses of vaccine in primary study, Dose 2 - primary study, Dose 3 - booster study within predefined window, had at least 1 valid immunogenicity result from blood sample collected within appropriate window at 1 month after Dose 3, were negative for both SARS-CoV-2 test at Dose 1,1-month post Dose 2, 3, and had no other protocol deviations determined by clinician. Here, N = participants evaluable for this outcome measure.

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.

Time frame: 1 Month after Dose 2 of primary study

Population: Booster evaluable immunogenicity population: Participants who received 2 doses of vaccine in primary study, Dose 2 - primary study, Dose 3 - booster study within predefined window, had at least 1 valid immunogenicity result from blood sample collected within appropriate window at 1 month after Dose 3, were negative for both SARS-CoV-2 test at Dose 1,1-month post Dose 2, 3, and had no other protocol deviations determined by clinician. Here, N = participants evaluable for this outcome measure.

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.

Time frame: 1 Month after Dose 3

Population: Booster evaluable immunogenicity population: Participants who received 2 doses of vaccine in primary study, Dose 2 - primary study, Dose 3 - booster study within predefined window, had at least 1 valid immunogenicity result from blood sample collected within appropriate window at 1 month after Dose 3, were negative for both SARS-CoV-2 test at Dose 1,1-month post Dose 2, 3, and had no other protocol deviations determined by clinician. Here, N = participants evaluable for this outcome measure.

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.

Time frame: 1 Week after Dose 3

Population: Booster evaluable immunogenicity population: Participants who received 2 doses of vaccine in primary study, Dose 2 - primary study, Dose 3 - booster study within predefined window, had at least 1 valid immunogenicity result from blood sample collected within appropriate window at 1 month after Dose 3, were negative for both SARS-CoV-2 test at Dose 1,1-month post Dose 2, 3, and had no other protocol deviations determined by clinician. Here, N = participants evaluable for this outcome measure.

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.

Time frame: Baseline (prior to Dose 1 of Primary study)

Population: Booster evaluable immunogenicity population: Participants who received 2 doses of vaccine in primary study, Dose 2 - primary study, Dose 3 - booster study within predefined window, had at least 1 valid immunogenicity result from blood sample collected within appropriate window at 1 month after Dose 3, were negative for both SARS-CoV-2 test at Dose 1,1-month post Dose 2, 3, and had no other protocol deviations determined by clinician. Here, N = participants evaluable for this outcome measure.

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.

Time frame: Before Dose 3

Population: Booster evaluable immunogenicity population: Participants who received 2 doses of vaccine in primary study, Dose 2 - primary study, Dose 3 - booster study within predefined window, had at least 1 valid immunogenicity result from blood sample collected within appropriate window at 1 month after Dose 3, were negative for both SARS-CoV-2 test at Dose 1,1-month post Dose 2, 3, and had no other protocol deviations determined by clinician. Here, N = participants evaluable for this outcome measure.

An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly or that was considered to be an important medical event.

Time frame: Day 1 of Dose 1 up to 1 Month after Dose 2 (for a maximum of 2 months)

Population: Safety population included all randomized participants who received at least 1 dose of the study intervention.

An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly or that was considered to be an important medical event.

Time frame: From Dose 3 to 1 Month after Dose 3 (for a maximum of 35 days)

Population: Safety population included all randomized participants who received Dose 3 of the study intervention.

Local reactions were collected by the participant using an electronic diary. Local reactions included redness, swelling, and pain at injection site after each vaccination. Redness, swelling, and pain at injection site after any dose were reported.

Time frame: Within 7 days after any dose

Population: Safety population included all randomized participants who received at least 1 dose of the study intervention. 1 participant randomized to US Lot 1 was administered US Lot 1 for Dose 1 and US Lot 3 for Dose 2, therefore, the participant was included in both reporting groups (US Lot 1 and US Lot 3).

Local reactions were collected by the participant using an electronic diary. Local reactions included redness, swelling, and pain at injection site after Dose 1. Redness, swelling, and pain at injection site after Dose 1 were reported.

Time frame: Within 7 days after Dose 1

Population: Safety population included all randomized participants who received at least 1 dose of the study intervention. Here, Overall Number of Participants Analyzed= participants evaluable for this outcome measure.

Local reactions were collected by the participant using an electronic diary. Local reactions included redness, swelling, and pain at injection site after Dose 2. Redness, swelling, and pain at injection site after Dose 2 were reported.

Time frame: Within 7 days after Dose 2

Population: Safety population included all randomized participants who received at least 1 dose of the study intervention. Here, Overall Number of Participants Analyzed= participants evaluable for this outcome measure.

Local reactions were collected by the participant using an electronic diary. Local reactions included redness, swelling, and pain at injection site after Dose 3. Redness, swelling, and pain at injection site after Dose 3 were reported.

Time frame: Within 7 days after Dose 3

Population: Safety population included all randomized participants who received dose 3 of the study intervention.

Seroresponse was defined as \>=4-fold increase from baseline (before Dose 1 in primary study) to the specified time point.

Time frame: 1 Month after Dose 3

Population: Data for this outcome was not analyzed as the immunogenicity samples were not tested for SARS-CoV-2 B.1.351-strain at Baseline as the South African strain was no longer of clinical interest and required responses have been well understood from other studies.

Seroresponse was defined as \>=4-fold increase from baseline (before Dose 1 in primary study) to the specified time point.

Time frame: 1 Week after Dose 3

Population: Data for this outcome was not analyzed as the immunogenicity samples were not tested for SARS-CoV-2 B.1.351-strain at Baseline as the South African strain was no longer of clinical interest and required responses have been well understood from other studies.

Seroresponse was defined as \>=4-fold increase from baseline (before Dose 1 in primary study) to the specified time point.

Time frame: 1 Month after Dose 2

Population: Data for this outcome was not analyzed as the immunogenicity samples were not tested for SARS-CoV-2 B.1.351-strain at baseline and 1 month after dose 2 as the South African strain was no longer of clinical interest and required responses have been well understood from other studies.

Seroresponse was defined as \>=4-fold increase from baseline (before Dose 1 in primary study) to the specified time point.

Time frame: Before Dose 3

Population: Data for this outcome was not analyzed as the immunogenicity samples were not tested for SARS-CoV-2 B.1.351-strain at Baseline as the South African strain was no longer of clinical interest and required responses have been well understood from other studies.

Seroresponse was defined as \>=4-fold increase from baseline (before Dose 1 in primary study) to the specified time point. If the baseline measurement was below LLOQ, a post vaccination measurement of \>=4\*LLOQ was considered a seroresponse. Exact 2-sided 95% CI was based on the Clopper and Pearson method.

Time frame: 1 Month after Dose 3

Population: Booster evaluable immunogenicity population: Participants who received 2 doses of vaccine in primary study, Dose 2 - primary study, Dose 3 - booster study within predefined window, had at least 1 valid immunogenicity result from blood sample collected within appropriate window at 1 month after Dose 3, were negative for both SARS-CoV-2 test at Dose 1,1-month post Dose 2, 3, and had no other protocol deviations determined by clinician. Here, N = participants evaluable for this outcome measure.

Seroresponse was defined as \>=4-fold increase from baseline (before Dose 1 in primary study) to the specified time point. If the baseline measurement was below LLOQ, a post vaccination measurement of \>=4\*LLOQ was considered a seroresponse. Exact 2-sided 95% CI was based on the Clopper and Pearson method.

Time frame: 1 Week after Dose 3

Population: Booster evaluable immunogenicity population: Participants who received 2 doses of vaccine in primary study, Dose 2 - primary study, Dose 3 - booster study within predefined window, had at least 1 valid immunogenicity result from blood sample collected within appropriate window at 1 month after Dose 3, were negative for both SARS-CoV-2 test at Dose 1,1-month post Dose 2, 3, and had no other protocol deviations determined by clinician. Here, N = participants evaluable for this outcome measure.

Seroresponse was defined as greater than equal to (\>=) 4-fold increase from baseline (before Dose 1 in primary study) to the specified time point. If the baseline measurement was below LLOQ, a post vaccination measurement of \>=4\*LLOQ was considered a seroresponse. Exact 2-sided 95% CI was based on the Clopper and Pearson method.

Time frame: 1 Month after Dose 2

Population: Booster evaluable immunogenicity population: Participants who received 2 doses of vaccine in primary study, Dose 2 - primary study, Dose 3 - booster study within predefined window, had at least 1 valid immunogenicity result from blood sample collected within appropriate window at 1 month after Dose 3, were negative for both SARS-CoV-2 test at Dose 1,1-month post Dose 2, 3, and had no other protocol deviations determined by clinician. Here, N = participants evaluable for this outcome measure.

Seroresponse was defined as \>=4-fold increase from baseline (before Dose 1 in primary study) to the specified time point. If the baseline measurement was below LLOQ, a post vaccination measurement of \>=4\*LLOQ was considered a seroresponse. Exact 2-sided 95% CI was based on the Clopper and Pearson method.

Time frame: Before Dose 3

Population: Booster evaluable immunogenicity population: Participants who received 2 doses of vaccine in primary study, Dose 2 - primary study, Dose 3 - booster study within predefined window, had at least 1 valid immunogenicity result from blood sample collected within appropriate window at 1 month after Dose 3, were negative for both SARS-CoV-2 test at Dose 1,1-month post Dose 2, 3, and had no other protocol deviations determined by clinician. Here, N = participants evaluable for this outcome measure.

Systemic events were reported using an electronic diary. Fever was defined as temperature \>=38.0 C and categorized as \>=38.0 to 38.4 C; \>38.4 to 38.9 C; \>38.9 to 40.0 C; \>40.0 C. Systemic events including fever, fatigue, headache, chills, new or worsened muscle pain, new or worsened joint pain, vomiting, diarrhea, and use of antipyretic/analgesic medication after any dose were reported.

Time frame: Within 7 days after any dose

Population: Safety population included all randomized participants who received at least 1 dose of the study intervention. 1 participant randomized to US Lot 1 was administered US Lot 1 for Dose 1 and US Lot 3 for Dose 2, therefore, the participant was included in both reporting groups (US Lot 1 and US Lot 3).

Systemic events were reported using an electronic diary. Fever was defined as temperature \>=38.0 degree Celsius (C) and categorized as \>=38.0 to 38.4 C; \>38.4 to 38.9 C; \>38.9 to 40.0 C; \>40.0 C. Systemic events including fever, fatigue, headache, chills, new or worsened muscle pain, new or worsened joint pain, vomiting, diarrhea, and use of antipyretic/analgesic medication after Dose 1 were reported.

Time frame: Within 7 days after Dose 1

Population: Safety population included all randomized participants who received at least 1 dose of the study intervention. Here, Overall Number of Participants Analyzed= participants evaluable for this outcome measure.

Systemic events were reported using an electronic diary. Fever was defined as temperature \>=38.0 C and categorized as \>=38.0 to 38.4 C; \>38.4 to 38.9 C; \>38.9 to 40.0 C; \>40.0 C. Systemic events including fever, fatigue, headache, chills, new or worsened muscle pain, new or worsened joint pain, vomiting, diarrhea, and use of antipyretic/analgesic medication after Dose 2 were reported.

Time frame: Within 7 days after Dose 2

Population: Safety population included all randomized participants who received at least 1 dose of the study intervention. Here, Overall Number of Participants Analyzed= participants evaluable for this outcome measure.

Systemic events were reported using an electronic diary. Fever was defined as temperature \>=38.0 C and categorized as \>=38.0 to 38.4 C; \>38.4 to 38.9 C; \>38.9 to 40.0 C; \>40.0 C. Systemic events including fever, fatigue, headache, chills, new or worsened muscle pain, new or worsened joint pain, vomiting, diarrhea, and use of antipyretic/analgesic medication after Dose 3 were reported.

Time frame: Within 7 days after Dose 3

Population: Safety population included all randomized participants who received dose 3 of the study intervention.

GMCs were calculated by exponentiating the mean logarithm of the concentrations and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5\* LLOQ.

Time frame: Baseline (before Dose 1), 1 Month after Dose 2

Population: Evaluable immunogenicity population: Participants who received 2 doses of vaccine in primary study, with Dose 2 received within predefined window, had at least 1 valid immunogenicity result from blood sample collected within an appropriate window at 1 month after Dose 2, were negative for both SARS-CoV-2 test during study and had no other protocol deviations determined by clinician. Here, N=participants evaluable for this outcome measure and n=participants evaluable at specified time points.

GMFRs were defined as ratios of the geometric mean concentration of IgG at 1 month after Dose 2 to the geometric mean concentration of IgG at Baseline. GMFRs were calculated by exponentiating the mean logarithm of fold rises and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5\*LLOQ.

Time frame: From Baseline (before Dose 1) up to 1 Month after Dose 2

Population: Evaluable immunogenicity population: Participants who received 2 doses of vaccine in primary study, with Dose 2 received within predefined window, had at least 1 valid immunogenicity result from blood sample collected within an appropriate window at 1 month after Dose 2, were negative for both SARS-CoV-2 test (RT-PCR and N-blinding antibody) during study and had no other protocol deviations determined by clinician. Here, N= participants evaluable for this outcome measure.

GMFRs were defined as ratios of the geometric mean titers of SARS-CoV-2 at 1 month after Dose 2 to the geometric mean titers of SARS-CoV-2 at Baseline. GMFRs were calculated by exponentiating the mean logarithm of fold rises and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5\* LLOQ.

Time frame: From Baseline (before Dose 1) up to 1 Month after Dose 2

Population: Evaluable immunogenicity population: Participants who received 2 doses of vaccine in primary study, with Dose 2 received within predefined window, had at least 1 valid immunogenicity result from blood sample collected within an appropriate window at 1 month after Dose 2, were negative for both SARS-CoV-2 test (RT-PCR and N-blinding antibody) during study and had no other protocol deviations determined by clinician. Here, N= participants evaluable for this outcome measure.

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.

Time frame: Baseline (before Dose 1), 1 Month after Dose 2

Population: Evaluable immunogenicity population: Participants who received 2 doses of vaccine in primary study, with Dose 2 received within predefined window, had at least 1 valid immunogenicity result from blood sample collected within an appropriate window at 1 month after Dose 2, were negative for both SARS-CoV-2 test (RT-PCR and N-blinding antibody) during study and had no other protocol deviations determined by clinician. Here, N= participants evaluable for this outcome measure.