A Study to Evaluate the Safety, Tolerability, and Immunogenicity of Combined Modified RNA Vaccine Candidates Against COVID-19 and Influenza

BioNTech SE1,019 enrolled

Overview

Substudy A: This is a Phase 1 randomized, open-label study to describe the safety and immunogenicity of up to 3 dose- level combinations of modRNA quadrivalent influenza vaccine (qIRV (22/23)) and bivalent BNT162b2 (original/Omi BA.4/BA.5). Participants will receive either: * qIRV (22/23)/bivalent BNT162b2 (original/Omi BA.4/BA.5), at 1 of the 3 dose-level combinations * qIRV (22/23) at dose level 1, * qIRV (22/23) at dose level 2, or * bivalent BNT162b2 (original/Omi BA.4/BA.5) at dose level 1 administered concurrently in the opposite arm to commercially licensed quadrivalent influenza vaccine (QIV). Substudy B: This Phase 1/2 study will describe the safety, tolerability, and immunogenicity of quadrivalent influenza vaccine (qIRV)/bivalent BNT162b2 (original/Omi BA.4/BA.5), trivalent influenza vaccine (tIRV)/bivalent BNT162b2 (original/Omi BA.4/BA.5), and bivalent influenza vaccine (bIRV)/bivalent BNT162b2 (original/Omi BA.4/BA.5) when given concurrently with licensed quadrivalent influenza vaccine (QIV).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Enrollment

1,019

Conditions

Influenza, Human COVID-19

Interventions

bivalent BNT162b2 (original/Omi BA.4/BA.5)BIOLOGICAL

Intramuscular injection

qIRV (22/23)BIOLOGICAL

Intramuscular injection

QIVBIOLOGICAL

Intramuscular injection

bIRVBIOLOGICAL

Intramuscular injection

tIRVBIOLOGICAL

Intramuscular injection

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

SSA: Inclusion Criteria: * Male or female participants 18 years of age and older * Participants who are willing and able to comply with all scheduled visits, investigational plan, laboratory tests, lifestyle considerations, and other study procedures. * Healthy participants who are determined by medical history, physical examination (if required), and clinical judgment of the investigator to be eligible for inclusion in the study. * Capable of giving signed informed consent as described in the protocol. * For participants 18 through 64 years of age: participants who have received 3 prior doses of 30 µg BNT162b2, with the last dose being 150 to 365 days before Visit 1 (Day 1). * For participants 65 years of age and older: participants who have received 4 or 5 prior doses of a modRNA SARS-CoV-2 vaccine, with the last dose being a bivalent vaccine, 120 days to 365 days before Visit 1 (Day 1). * For Participants 65 years of age and older: receipt of licensed influenza vaccination for the 2022-2023 northern hemisphere season 120 days or more before study intervention administration. SSA: Exclusion Criteria: * History of severe adverse reaction associated with any vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s). * Immunocompromised individuals with known or suspected immunodeficiency. * Bleeding diathesis or condition associated with prolonged bleeding. * Women who are pregnant or breastfeeding. * Allergy to egg proteins (egg or egg products) or chicken proteins. * Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study. * Receipt of chronic systemic treatment with known immunosuppressant medications (including cytotoxic agents or systemic corticosteroids), or radiotherapy, within 60 days before enrollment through conclusion of the study. * Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies, from 60 days before study intervention administration, or planned receipt throughout the study. * For participants 18 through 64 years of age: vaccination with any investigational or licensed influenza vaccine within 6 months (175 days) before study intervention administration. * Participation in other studies involving a study intervention within 28 days before randomization. Anticipated participation in other studies within 28 days after receipt of study intervention in this study. * Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members. * Participation in strenuous or endurance exercise through Visit 3 of the study. * Prior history of heart disease. * Any abnormal screening troponin I laboratory value. * Screening 12-lead ECG that, as judged by the investigator, is consistent with probable or possible myocarditis or pericarditis, or demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results. SSB: Inclusion Criteria * Male or female participants 18 years of age and older * Participants who are willing and able to comply with all scheduled visits, investigational plan, laboratory tests, lifestyle considerations, and other study procedures. * Healthy participants who are determined by medical history, physical examination (if required), and clinical judgment of the investigator to be eligible for inclusion in the study. * Capable of giving signed informed consent as described in the protocol. * Participants who have received at least 3 prior US-authorized mRNA COVID-19 vaccines, with the last dose being an updated (bivalent) vaccine given at least 150 days before Day 1. SSB: Exclusion Criteria * Medical or psychiatric condition, including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality, that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study. * History of severe adverse reaction associated with any vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s). * Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination. * Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection * Receipt of chronic systemic treatment with known immunosuppressant medications (including cytotoxic agents or systemic corticosteroids), or radiotherapy, within 60 days before enrollment through conclusion of the study. * Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies, from 60 days before study intervention administration, or planned receipt throughout the study. * Vaccination with any investigational or licensed influenza vaccine within 6 months (175 days) before study intervention administration, or ongoing receipt of chronic antiviral therapy with activity against influenza * Participation in other studies involving administration of a study intervention within 28 days prior to, and/or during, participation in this study. * Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members. * Initial enrollment only: Participation in strenuous or endurance exercise through Visit 3 (initial enrollment phase). * Initial enrollment only: Prior history of heart disease of concern * Initial enrollment only: Screening 12-lead ECG that, as judged by the investigator, is consistent with probable or possible myocarditis or pericarditis, or demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results.

Locations (59)

North Alabama Research Center

Athens, Alabama, United States

The Heart Center

Athens, Alabama, United States

HOPE Research Institute

Phoenix, Arizona, United States

The Pain Center of Arizona

Phoenix, Arizona, United States

Orange County Research Center

Lake Forest, California, United States

Outcomes

Primary Outcomes

SSA: Percentage of Participants With Local Reactions up to 7 Days Following Vaccination (18-64 Years)

Local reactions included pain at the injection site, redness and swelling and were recorded by participants in an electronic diary. Redness and swelling were measured and recorded in measuring device units, where 1 measuring device unit=0.5 centimeter (cm). Redness and swelling were graded as mild (Grade 1): greater than (\>) 2.0 cm to 5.0 cm; moderate (Grade 2): \>5.0 cm to 10.0 cm; severe (Grade 3): \>10 cm; potentially life-threatening (Grade 4): necrosis or exfoliative dermatitis (redness) and necrosis (swelling). Pain at injection site was graded as mild (Grade 1): did not interfere with activity; moderate (Grade 2): interfered with activity; severe (Grade 3): prevented daily activity and potentially life-threatening (Grade 4): emergency room visit or hospitalization for severe pain. Grade 4 reactions were classified by the investigator or medically qualified person. Percentage of participants with any local reactions were reported in this outcome measure.

Time frame: SSA: From Day 1 to Day 7 after Vaccination

SSA: Percentage of Participants With Local Reactions up to 7 Days Following Vaccination (>=65 Years)

Local reactions included pain at the injection site, redness and swelling and were recorded by participants in an electronic diary. Redness and swelling were measured and recorded in measuring device units, where 1 measuring device unit=0.5 cm. Redness and swelling were graded as mild (Grade 1): \>2.0 cm to 5.0 cm; moderate (Grade 2): \>5.0 cm to 10.0 cm; severe (Grade 3): \>10 cm; potentially life-threatening (Grade 4): necrosis or exfoliative dermatitis. Pain at injection site was graded as mild (Grade 1): did not interfere with activity; moderate (Grade 2): interfered with activity; severe (Grade 3): prevented daily activity and potentially life-threatening (Grade 4): emergency room visit or hospitalization for severe pain. Grade 4 reactions were classified by the investigator or medically qualified person. Percentage of participants with any local reactions were reported in this outcome measure.

Time frame: SSA: From Day 1 to Day 7 after Vaccination

SSA: Percentage of Participants With Systemic Events up to 7 Days Following Vaccination (18-64 Years)

Systemic events included fever, vomiting, diarrhea, headache, fatigue, chills, new or worsened muscle pain and new or worsened joint pain. Events were recorded by participants in an electronic diary. Fever defined as oral temperature \>=38.0 deg C and categorized as\>=38.0 to 38.4 deg C, \>38.4 to 38.9 deg C, \>38.9 to 40.0 deg C and \>40.0 deg C. Vomiting graded as: G1: 1-2 times in 24 h; G2: \>2 times in 24h; G3: required IV hydration. Diarrhea graded as: G1: 2-3 loose stools in 24h; G2: 4-5 loose stools in 24h; G3: 6 or more loose stools in 24h.Headache, fatigue, chills, new/worsened muscle pain and new/worsened joint pain: G1: didn't interfere with activity; G2: some interference with activity; G3: prevented daily routine activity. For all systemic events except fever, Grade 4=emergency room visit or hospitalization. Grade 4 events were classified by the investigator. Percentage of participants with any systemic events were reported in this outcome measure.

Time frame: SSA: From Day 1 to Day 7 after Vaccination

SSA: Percentage of Participants With Systemic Events up to 7 Days Following Vaccination (>=65 Years)

Time frame: SSA: From Day 1 to Day 7 after Vaccination

SSA: Percentage of Participants Reporting AEs From Vaccination Through 4 Weeks After Vaccination (18-64 Years)

An adverse event (AE) was defined as any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. AEs included both serious and all non-serious AEs. An SAE was defined as any untoward medical occurrence that, at any dose, met one or more of the following criteria - resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect and was a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic and other important medical event. Only AEs collected by non-systematic assessment (excluding local reactions and systematic events) were included in this outcome measure.

Time frame: SSA: From Vaccination on Day 1 through 4 Weeks after Vaccination

SSA: Percentage of Participants Reporting Adverse Events From Vaccination Through 4 Weeks After Vaccination (>=65 Years)

An AE was defined as any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. AEs included both serious and all non-serious AEs. An SAE was defined as any untoward medical occurrence that, at any dose, met one or more of the following criteria - resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect and was a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic and other important medical event. Only AEs collected by non-systematic assessment (excluding local reactions and systematic events) were included in this outcome measure.

Time frame: SSA: From Vaccination on Day 1 through 4 Weeks after Vaccination

SSA: Percentage of Participants Reporting Serious Adverse Events (SAEs) From Vaccination Through 6 Months After Vaccination (18-64 Years)

An SAE was defined as any untoward medical occurrence that, at any dose, met one or more of the following criteria - resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect and was a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic and other important medical event.

Time frame: SSA: From Vaccination on Day 1 through 6 Months after Vaccination

SSA: Percentage of Participants Reporting SAEs From Vaccination Through 6 Months After Vaccination (>=65 Years)

Time frame: SSA: From Vaccination on Day 1 through 6 Months after Vaccination

SSA: Percentage of Participants With Abnormal Serum Troponin 1 Laboratory Values at 2 Days After Vaccination (18-64 Years)

An abnormal troponin 1 result was defined as any troponin 1 level \>=0.30 nanogram per milliliter.

Time frame: SSA: 2 Days after Vaccination

SSA: Percentage of Participants With Abnormal Serum Troponin 1 Laboratory Values at 2 Days After Vaccination (>=65 Years)

An abnormal troponin 1 result was defined as any troponin 1 level \>=0.30 nanogram per milliliter.

Time frame: SSA: 2 Days after Vaccination

SSA: Percentage of Participants With Abnormal Serum Troponin 1 Laboratory Values at 1 Week After Vaccination (18-64 Years)

An abnormal troponin 1 result was defined as any troponin 1 level \>=0.30 nanogram per milliliter.

Time frame: SSA: 1 Week After Vaccination

SSA: Percentage of Participants With Abnormal Serum Troponin 1 Laboratory Values at 1 Week After Vaccination (>=65 Years)

An abnormal troponin 1 result was defined as any troponin 1 level \>=0.30 nanogram per milliliter.

Time frame: SSA: 1 Week After Vaccination

SSA: Percentage of Participants With New Electrocardiogram (ECG) Abnormalities at 2 Days After Vaccination (18-64 Years)

An ECG abnormality was defined as any new abnormality that, as judged by a cardiologist, was consistent with probable or possible myocarditis or pericarditis, including: sustained atrial or ventricular arrhythmias, second-degree Mobitz Type II or worse atrioventricular block, new bundle branch block and diffuse ST-segment elevation or PR-segment inversion, compatible with pericarditis.

Time frame: SSA: 2 Days after Vaccination

SSA: Percentage of Participants With New ECG Abnormalities at 2 Days After Vaccination (>=65 Years)

Time frame: SSA: 2 Days after Vaccination

SSA: Percentage of Participants With New ECG Abnormalities at 1 Week After Vaccination (18-64 Years)

Time frame: SSA: 1 Week after Vaccination

SSA: Percentage of Participants With New ECG Abnormalities at 1 Week After Vaccination (>=65 Years)

Time frame: SSA: 1 Week after Vaccination

SSB: Percentage of Participants With Abnormal Serum Troponin 1 Laboratory Values at 2 Days After Vaccination (18- 64 Years)

An abnormal troponin 1 result was defined as any troponin 1 level \>=0.30 nanogram per milliliter.

Time frame: SSB: 2 Days after Vaccination

SSB: Percentage of Participants With Abnormal Serum Troponin 1 Laboratory Values at 1 Week After Vaccination (18- 64 Years)

An abnormal troponin 1 result was defined as any troponin 1 level \>=0.30 nanogram per milliliter.

Time frame: SSB: 1 Week after Vaccination

SSB: Percentage of Participants With New ECG Abnormalities at 2 Days After Vaccination (18- 64 Years)

Time frame: SSB: 2 Days after Vaccination

SSB: Percentage of Participants With New ECG Abnormalities at 1 Week After Vaccination (18- 64 Years)

Time frame: SSB: 1 Week after Vaccination

SSB: Percentage of Participants With Local Reactions up to 7 Days Following Vaccination (18- 64 Years)

Local reactions included pain at the injection site, redness and swelling and were recorded by participants in an electronic diary. Redness and swelling were measured and recorded in measuring device units, where 1 measuring device unit=0.5 cm. Redness and swelling were graded as mild (Grade 1): \>2.0 cm to 5.0 cm; moderate (Grade 2): \>5.0 cm to 10.0 cm; severe (Grade 3): \>10 cm; potentially life-threatening (Grade 4): necrosis or exfoliative dermatitis. Pain at injection site was graded as mild (Grade 1): did not interfere with activity; moderate (Grade 2): interfered with activity; severe (Grade 3): prevented daily activity and potentially life-threatening (Grade 4): emergency room visit or hospitalization for severe pain. Grade 4 reactions were classified by the investigator or medically qualified person. Percentage of participants with any local reactions were reported in this outcome measure.

Time frame: SSB: From Day 1 to Day 7 after Vaccination

SSB: Percentage of Participants With Systemic Events up to 7 Days Following Vaccination (18- 64 Years)

Systemic events included fever, vomiting, diarrhea, headache, fatigue, chills, new or worsened muscle pain and new or worsened joint pain. Events were recorded by participants in an electronic diary. Fever defined as oral temperature \>=38.0 deg C and categorized as \>=38.0 to 38.4 deg C, \>38.4 to 38.9 deg C, \>38.9 to 40.0 deg C and \>40.0 deg C. Vomiting graded as: G1: 1-2 times in 24 h; G2: \>2 times in 24h; G3: required IV hydration. Diarrhea graded as: G1: 2-3 loose stools in 24h; G2: 4-5 loose stools in 24h; G3: 6 or more loose stools in 24h. Headache, fatigue, chills, new/worsened muscle pain and new/worsened joint pain: G1: didn't interfere with activity; G2: some interference with activity; G3: prevented daily routine activity. For all systemic events except fever, Grade 4=emergency room visit or hospitalization. Grade 4 events were classified by the investigator. Percentage of participants with any systemic events were reported in this outcome measure.

Time frame: SSB: From Day 1 to Day 7 after Vaccination

SSB: Percentage of Participants Reporting AEs From Vaccination Through 4 Weeks After Vaccination (18- 64 Years)

Time frame: SSB: From Vaccination on Day 1 through 4 Weeks after Vaccination

SSB: Percentage of Participants Reporting SAEs From Vaccination Through 6 Months After Vaccination (18- 64 Years)

Time frame: SSB: From Vaccination on Day 1 through 6 Months after Vaccination

Secondary Outcomes

SSA: Geometric Mean Titers (GMTs) of Strain-Specific Hemagglutination Inhibition (HAI) Before Vaccination and at 4 Weeks After Vaccination (18- 64 Years)

GMTs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the concentrations and the corresponding CIs (based on the Student t distribution). Assay results below the lower limit of quantitation (LLOQ) were set to 0.5\*LLOQ. Data is reported for following strains: A/Wisconsin, A/Darwin, B/Austria and B/Phuket.

Time frame: SSA: Before Vaccination and 4 Weeks after Vaccination

SSA: GMTs of Strain-Specific HAI Before Vaccination and at 4 Weeks After Vaccination (>=65 Years)

GMTs and 2-sided 95% CIs 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. Data is reported for following strains: A/Wisconsin, A/Darwin, B/Austria and B/Phuket.

Time frame: SSA: Before Vaccination and 4 Weeks after Vaccination

SSA: Geometric Mean Fold Rise (GMFRs) of Strain-Specific HAI From Before Vaccination to 4 Weeks After Vaccination (18- 64 Years)

GMFRs and the corresponding 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the fold rises and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5\*LLOQ. When pre-vaccination assay results were lower than the LLOQ and the post-vaccination results were greater than or equal to the LLOQ, the pre-vaccination assay results were set to LLOQ for the GMFR calculation. Data is reported for following strains: A/Wisconsin, A/Darwin, B/Austria and B/Phuket.

Time frame: SSA: Before Vaccination to 4 Weeks after Vaccination

SSA: GMFRs of Strain-Specific HAI From Before Vaccination to 4 Weeks After Vaccination (>=65 Years)

Data from ClinicalTrials.gov

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Orange County Heart Institute

Orange, California, United States

California Research Foundation

San Diego, California, United States

Orange County Research Center

Tustin, California, United States

Proactive Clinical Research,LLC

Fort Lauderdale, Florida, United States

Finlay Medical Research

Greenacres City, Florida, United States

...and 49 more locations

Time frame: SSA: Before Vaccination to 4 Weeks after Vaccination

SSA: Percentage of Participants Achieving HAI Seroconversion for Each Strain at 4 Weeks After Vaccination (18- 64 Years)

Seroconversion was defined as an HAI titer \<1:10 prior to vaccination and \>=1:40 at the time point of interest, or an HAI titer of \>=1:10 prior to vaccination with a 4-fold rise at the time point of interest. Exact 2-sided 95% CI was based on the Clopper and Pearson method. Data is reported for following strains: A/Wisconsin, A/Darwin, B/Austria and B/Phuket.

Time frame: SSA: 4 Weeks after Vaccination

SSA: Percentage of Participants Achieving HAI Seroconversion for Each Strain at 4 Weeks After Vaccination (>=65 Years)

Time frame: SSA: 4 Weeks after Vaccination

SSA: Percentage of Participants With Strain Specific HAI Titers Greater Than or Equal to (>=) 1:40 Before Vaccination and at 4 Weeks After Vaccination (18- 64 Years)

Percentage of participants with HAI titer \>=1:40 for each strain before vaccination and 4 weeks after vaccination is presented in this outcome measure. Exact 2-sided 95% CI was based on the Clopper and Pearson method. Data is reported for following strains: A/Wisconsin, A/Darwin, B/Austria and B/Phuket.

Time frame: SSA: Before Vaccination and at 4 Weeks after Vaccination

SSA: Percentage of Participants With Strain Specific HAI Titers >= 1:40 Before Vaccination and at 4 Weeks After Vaccination (>=65 Years)

Time frame: SSA: Before Vaccination and at 4 Weeks After Vaccination

SSA: Percentage of Participants Achieving HAI Seroconversion for All Strains at 4 Weeks After Vaccination (18- 64 Years)

Seroconversion was defined as an HAI titer \<1:10 prior to vaccination and \>=1:40 at the time point of interest, or an HAI titer of \>=1:10 prior to vaccination with a 4-fold rise at the time point of interest. Exact 2-sided 95% CI was based on the Clopper and Pearson method. Data is reported combined for all strains (A/Wisconsin, A/Darwin, B/Austria and B/Phuket).

Time frame: SSA: 4 Weeks after Vaccination

SSA: Percentage of Participants Achieving HAI Seroconversion for All Strains at 4 Weeks After Vaccination (>=65 Years)

Seroconversion was defined as an HAI titer \<1:10 prior to vaccination and \>=1:40 at the time point of interest, or an HAI titer of \>=1:10 prior to vaccination with a 4-fold rise at the time point of interest. Exact 2-sided 95% CI was based on the Clopper and Pearson method. Data is reported combined for all strains (A/Wisconsin, A/Darwin, B/Austria and B/Phuket).

Time frame: SSA: 4 Weeks after Vaccination

SSA: Percentage of Participants With HAI Titers >= 1.40 for All Strain at 4 Weeks After Vaccination (18- 64 Years)

Percentage of participants achieving HAI titers \>= 1:40 for each strain at 4 weeks after last vaccination is reported in this outcome measure. Exact 2-sided CI was based on the Clopper and Pearson method. Data is reported combined for all strains (A/Wisconsin, A/Darwin, B/Austria and B/Phuket).

Time frame: SSA: 4 Weeks after Vaccination

SSA: Percentage of Participants With HAI Titers >= 1.40 for All Strain at 4 Weeks After Vaccination (>=65 Years)

Time frame: SSA: 4 Weeks after Vaccination

SSA: GMTs of SARS-CoV-2 Omicron (BA.4/BA.5)- Neutralizing Titers and SARS-CoV-2-Reference-Strain Neutralizing Titers Before Vaccination and at 4 Weeks After Vaccination (18- 64 Years)

GMT of SARS-CoV-2 Omicron (BA.4/BA.5)- neutralizing titers and SARS-CoV-2 reference strain (BNT162b2 Original \[ancestral strain: Wuhan-Hu-1; USA-WA1/2020\]) neutralizing titers before study vaccination and at 4 week after vaccination were reported in this outcome measure. GMT and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5\*LLOQ.

Time frame: SSA: Before Vaccination and 4 Weeks after Vaccination

SSA: GMTs of SARS-CoV-2 Omicron (BA.4/BA.5)- Neutralizing Titers and SARS-CoV-2-Reference-Strain Neutralizing Titers Before Vaccination and at 4 Weeks After Vaccination (>=65 Years)

GMT of SARS-CoV-2 Omicron (BA.4/BA.5)- neutralizing titers and SARS-CoV-2 reference strain (BNT162b2 Original \[ancestral strain: Wuhan-Hu-1; USA-WA1/2020\]) neutralizing titers before study vaccination and at 4 week after vaccination was reported in this outcome measure. GMT and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5\*LLOQ.

Time frame: SSA: Before Vaccination and 4 Weeks after Vaccination

SSA: GMFR of SARS-CoV-2 Omicron (BA.4/BA.5)- Neutralizing Titers and SARS-CoV-2-Reference-Strain Neutralizing Titers Before Vaccination to 4 Weeks After Vaccination (18- 64 Years)

GMFR of SARS-CoV-2 Omicron (BA.4/BA.5)- neutralizing titers and SARS-CoV-2 reference strain (BNT162b2 Original \[ancestral strain: Wuhan-Hu-1; USA-WA1/2020\]) neutralizing titers before study vaccination to 4 week after vaccination was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rise and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5\*LLOQ.

Time frame: SSA: Before Vaccination to 4 Weeks after Vaccination

SSA: GMFR of SARS-CoV-2 Omicron (BA.4/BA.5)- Neutralizing Titers and SARS-CoV-2-Reference-Strain Neutralizing Titers Before Vaccination to 4 Weeks After Vaccination (>=65 Years)

Time frame: SSA: Before Vaccination to 4 Weeks after Vaccination

SSA: Percentage of Participants With Seroresponse Based on SARS-CoV-2 Omicron (BA.4/BA.5)- Neutralizing Titers and SARS-CoV-2-Reference-Strain Neutralizing Titers at 4 Weeks After Vaccination (18- 64 Years)

Seroresponse was defined as achieving \>= 4-fold rise from baseline (before study vaccination). If the baseline measurement was below the LLOQ, the postvaccination assay result of \>= 4\*LLOQ was considered a seroresponse. Exact 2-sided 95% CI, based on the Clopper and Pearson method. Percentage of participants achieving seroresponse Based on SARS-CoV-2 Omicron (BA.4/BA.5)- neutralizing titers and SARS-CoV-2-Reference-Strain (ancestral strain (Wuhan-Hu-1; USA-WA1/2020) neutralizing titers at 4 weeks after study vaccination was reported in this outcome measure.

Time frame: SSA: 4 Weeks after Vaccination

Time frame: SSA:4 Weeks after Vaccination

SSB: GMTs of Strain-Specific HAI Before Vaccination and at 4 Weeks After Vaccination (18- 64 Years)

GMTs and 2-sided 95% CIs 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. Data is reported for following strains: A/Wisconsin, A/Darwin, B/Austria, A/Cambodia and B/Phuket.

Time frame: SSB: Before Vaccination and 4 Weeks after Vaccination

SSB: GMFR of Strain-Specific HAI From Before Vaccination to 4 Weeks After Vaccination (18- 64 Years)

Time frame: SSB: Before Vaccination to 4 Weeks after Vaccination

SSB: Percentage of Participants Achieving HAI Seroconversion for Each Strain at 4 Weeks After Vaccination (18- 64 Years)

Time frame: SSB: 4 Weeks after Vaccination

SSB: Percentage of Participants With Strain Specific HAI Titers >=1:40 Before Vaccination and at 4 Weeks After Vaccination (18- 64 Years)

Time frame: SSB: Before Vaccination and at 4 Weeks after Vaccination

SSB: GMTs of SARS-CoV-2 Omicron (BA.4/BA.5)- Neutralizing Titers and SARS-CoV-2-Reference-Strain Neutralizing Titers Before Vaccination and at 4 Weeks After Vaccination (18- 64 Years)

GMT of SARS-CoV-2 Omicron (BA.4/BA.5)- neutralizing titers and SARS-CoV-2 reference strain (BNT162b2 Original \[ancestral strain: Wuhan-Hu-1; USA-WA1/2020\]) neutralizing titers before study vaccination and at 4 week after vaccination was reported in this outcome measure. GMT and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5\*LLOQ.

Time frame: SSB: Before Vaccination and at 4 Weeks after Vaccination

SSB: GMFR of SARS-CoV-2 Omicron (BA.4/BA.5)- Neutralizing Titers and SARS-CoV-2-Reference-Strain Neutralizing Titers From Before Vaccination to 4 Weeks After Vaccination (18- 64 Years)

Time frame: SSB: 4 Weeks after Vaccination

SSB: Percentage of Participants With Seroresponse Based on SARS-CoV-2 Omicron (BA.4/BA.5)- Neutralizing Titers and SARS-CoV-2-Reference-Strain Neutralizing Titers at 4 Weeks After Vaccination (18- 64 Years)

Time frame: SSB: 4 Weeks after Vaccination