A Study on the Immune Response and Safety of the Shingles Vaccine and the Influenza Vaccine When Either is Given to Healthy Adults at the Same Time or Following a COVID-19 Booster Vaccine

Study Overview
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Brief Summary
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The aim of this study was to evaluate the immune response and safety of both GlaxoSmithKline Biologicals SA's (GSK's) herpes zoster (HZ) subunit (su) vaccine in healthy adults 50 years of age (YOA) and older and quadrivalent seasonal influenza (Flu D-QIV) vaccine in healthy adults 18 YOA and older, when administered sequentially or co-administered with Moderna's mRNA-1273 booster vaccination against COVID-19.

Official Title
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A Phase III, Randomized, Open-label, Controlled, Multicenter Study to Evaluate the Immune Response and Safety of Both Herpes Zoster Subunit Vaccine in Healthy Adults Aged 50 Years and Older AND the Influenza Virus Vaccine in Healthy Adults Aged 18 Years and Older When Administered Sequentially or Coadministered With mRNA-1273 Booster Vaccination

Conditions
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Herpes Zoster

Intervention / Treatment
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* Biological: HZ/su
* Combination Product: Flu D-QIV
* Biological: mRNA-1273


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants who in the opinion of the investigator, can and who will comply with the requirements of the protocol (e.g., completion of the eDiaries, return for follow-up visits). Written informed consent obtained from the participant prior to performance of any study-specific procedure. Age at study entry: For HZ/su and mRNA-1273 booster cohort: A male or female aged 50 years or older at the time of randomization. For Flu D-QIV and mRNA-1273 booster cohort: A male or female aged 18 years or older at the time of enrollment. Healthy participants or medically stable patients as established by medical history and clinical examination at screening. A stable medical condition is defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 3 months before enrolment. Participants who have a documented previous mRNA-1273 primary vaccination series completed (i.e., both doses) at least 6 months prior to first vaccination. Female participants of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as pre-menarche, current bilateral tubal ligation or occlusion, documented total hysterectomy, bilateral ovariectomy, or bilateral salpingectomy, or post-menopause. Female participants of childbearing potential may be enrolled in the study, if the participant: Has practiced effective contraception for 1 month prior to study intervention administration, and Has a negative pregnancy test on the day of study intervention administration, and Has agreed to continue effective contraception during the study until 2 months after completion of the study vaccination series. Exclusion Criteria: Medical conditions Any clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the study or might confound post-study intervention administration safety assessments (e.g., tattoos overlying either study intervention administration site). History of any reaction or hypersensitivity likely to be exacerbated by any component of the study interventions, including a known history of severe allergic reaction (e.g., anaphylaxis) to any component of any of the study vaccines. Any history of Guillain-Barré syndrome. Any history of myocarditis or pericarditis. Acute or chronic clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by medical history or physical examination. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required). Hypersensitivity to latex. For HZ/su and mRNA-1273 booster cohort: history of Herpes Zoster. Prior/concomitant therapy Use of any investigational or non-registered product (drug, vaccine or medical device) other than the study intervention(s) during the period beginning 30 days before the first dose of study intervention(s) (Day -29 to Day 1), or their planned use during the study period. Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 30 days before first dose and ending 30 days after the last dose of study intervention administration. However, for HZ/su and mRNA-1273 booster cohort: licensed pneumococcal vaccines and non-replicating vaccines (i.e., inactivated and subunit vaccines, including inactivated and subunit influenza vaccines, with or without adjuvant for seasonal or pandemic flu) may be administered up until 8 days prior to dose 1 of HZ/su and/or dose 2 of HZ/su and/or at least 14 days after any dose of HZ/su. For Flu D-QIV and mRNA-1273 booster cohort: licensed pneumococcal vaccines and non-replicating vaccines (i.e., inactivated and subunit vaccines, other than influenza vaccines) may be administered up until 8 days prior to dose 1 of Flu D-QIV and/or at least 30 days after any dose of Flu D-QIV. For time interval between other routine vaccines with mRNA-1273 booster dose (administered in the study), local guidelines must be followed. In case emergency mass vaccination for an unforeseen public health threat (e.g., a pandemic) is organized by public health authorities outside the routine immunization program, the time period described above can be reduced if necessary for that mass vaccination vaccine, provided this vaccine is licensed and used according to its Product Information. Administration of long-acting immune-modifying drugs at any time during the study period (e.g., infliximab). Administration of immunoglobulins and/or any blood products or plasma derivatives during the period starting 3 months before the first dose of study intervention(s) up to 1 month post last dose or planned administration during the study period. Prior planned or chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting 3 months prior to the first vaccine. For corticosteroids, this will mean more than 14 days in total of prednisone ≥20 mg/day or equivalent is not allowed. Inhaled, intra-articular and topical steroids are allowed. For HZ/su and mRNA-1273 booster cohort: Previous vaccination against Herpes Zoster with the exception of receipt of live attenuated HZ vaccine. For Flu D-QIV and mRNA-1273 booster cohort: Administration of a seasonal influenza vaccine during the 6 months preceding entry into the study. Prior administration of an investigational or licensed coronavirus (SARS-CoV, MERS-CoV, SARS-CoV-2) vaccine except for mRNA-1273 vaccine. Any contraindication to the study intervention(s). Prior/concurrent clinical study experience • Planning to or concurrently participating in another clinical study (including current / planned simultaneous participation in another interventional study to prevent or treat COVID-19), at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational vaccine / product (drug or medical device). Other exclusions Pregnant or lactating female. Female planning to become pregnant or planning to discontinue contraceptive precautions within 2 months following last study vaccination. Indications of drug abuse or excess alcohol use as deemed by investigator to potentially confound safety assessments or render participant unable or unlikely to adhere to protocol requirements.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: HZ/suSeq Group<br>Participants randomized to HZ/suSeq Group received one mRNA-1273 booster dose administered at Day 1, followed by the first dose of HZ/su vaccine administered at Week 2 and the second dose of HZ/su vaccine administered at Week 10. | Biological: HZ/su<br>* 2 doses of HZ/su vaccine administered intramuscularly, either sequentially (HZ/suSeq Group) or simultaneously (HZ/suCoAd Group) with the mRNA-1273 booster dose. The second dose of HZ/su was administered 8 weeks after the first dose of HZ/su vaccine.<br>Biological: mRNA-1273<br>* 1 booster dose of mRNA-1273 vaccine administered intramuscularly at Day 1 (all groups).<br>|
| Experimental: HZ/suCoAd Group<br>Participants randomized to HZ/suCoAd Group received one mRNA-1273 booster dose co-administered with the first dose of HZ/su vaccine at Day 1, followed by the second dose of HZ/su vaccine administered at Week 8. | Biological: HZ/su<br>* 2 doses of HZ/su vaccine administered intramuscularly, either sequentially (HZ/suSeq Group) or simultaneously (HZ/suCoAd Group) with the mRNA-1273 booster dose. The second dose of HZ/su was administered 8 weeks after the first dose of HZ/su vaccine.<br>Biological: mRNA-1273<br>* 1 booster dose of mRNA-1273 vaccine administered intramuscularly at Day 1 (all groups).<br>|
| Active Comparator: FluD-QIVSeq Group<br>Participants randomized to FluD-QIVSeq Group received one mRNA-1273 booster dose at Day 1, followed by one dose of Flu D-QIV vaccine at Week 2. | Combination Product: Flu D-QIV<br>* 1 dose of Flu D-QIV vaccine administered intramuscularly, either sequentially (FluD-QIVSeq Group) or simultaneously (FluD-QIVCoAd Group) with the mRNA-1273 booster dose.<br>* Other names: Flu Quadrivalent Influenza Vaccine;Biological: mRNA-1273<br>* 1 booster dose of mRNA-1273 vaccine administered intramuscularly at Day 1 (all groups).<br>|
| Experimental: FluD-QIVCoAd Group<br>Participants randomized to FluD-QIVCoAd Group received one mRNA-1273 booster dose co-administered with one dose of Flu D-QIV vaccine at Day 1. | Combination Product: Flu D-QIV<br>* 1 dose of Flu D-QIV vaccine administered intramuscularly, either sequentially (FluD-QIVSeq Group) or simultaneously (FluD-QIVCoAd Group) with the mRNA-1273 booster dose.<br>* Other names: Flu Quadrivalent Influenza Vaccine;Biological: mRNA-1273<br>* 1 booster dose of mRNA-1273 vaccine administered intramuscularly at Day 1 (all groups).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-glycoprotein E (gE) Antibody Concentrations Expressed as Geometric Mean Concentrations (GMCs) in HZ/suSeq and HZ/suCoAd Groups, and Between-group Ratios | Anti-gE antibody concentrations were determined by enzyme-linked immunosorbent assay (ELISA) and expressed as GMCs in milli-international units per milliliter (mIU/mL). | At 1 month post-dose 2 of HZ/su vaccine administration (Week 14 for HZ/suSeq group and Week 12 for HZ/suCoAd group) | 
| Anti-S Protein Antibody Concentrations Expressed as GMCs in HZ/suSeq and HZ/suCoAd Groups, and Between-group Ratios | Anti-S antibody concentrations were determined by Multiplex Electrochemiluminescence assay and expressed as GMCs in arbitrary units per milliliter (AU/mL). | At 1 month post-mRNA-1273 booster dose administration (Week 4 for both HZ/suSeq and HZ/suCoAd groups) | 
| Anti-hemagglutinin Inhibition (HI) Antibody Titers Expressed as Geometric Mean Titers (GMTs) Against the 4 Influenza Strains in Flu D-QIV Vaccine in FluD-QIVSeq and FluD-QIVCoAd Groups, and Between-group Ratios | Antibody titers against the 4 influenza strains (A/H1N1 strain, A/H3N2 strain, B/Victoria lineage and B/Yamagata lineage) included in the FLU D-QIV vaccine were determined by hemagglutination inhibition and expressed as GMTs. | At 1 month post-Flu D-QIV vaccine dose administration (Week 6 for FluD-QIVSeq group and Week 4 for FluD-QIVCoAd group) | 
| Anti-S Protein Antibody Concentrations Expressed as GMCs in FluD-QIVSeq and FluD-QIVCoAd Groups, and Between-group Ratios | Anti-S antibody concentrations were determined by Multiplex Electrochemiluminescence assay and expressed as GMCs in AU/mL. | At 1 month post-mRNA-1273 booster dose administration (Week 4 for both FluD-QIVSeq and FluD-QIVCoAd groups) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Seroconverted for Anti-HI Antibodies Against the 4 Influenza Strains in Flu D-QIV Vaccine in FluD-QIVSeq and FluD-QIVCoAd Groups, and Between-group Differences | A participant seroconverted for anti-HI antibodies against the 4 influenza strains is defined as a participant having either a pre-vaccination HI titer below (<) 1:10 and a post-vaccination HI titer greater than or equal to (≥) 1:40, or a pre-vaccination HI titer ≥ 1:10 and at least a 4 fold greater post-vaccination HI titer. The 4 influenza strains assessed were A/H1N1 strain, A/H3N2 strain, B/Victoria lineage and B/Yamagata lineage. | At 1 month post-Flu D-QIV vaccine dose administration (Week 6 for FluD-QIVSeq group and Week 4 for FluD-QIVCoAd group) | 
| Percentage of Participants Seropositive for Anti-gE Antibodies in HZ/suSeq and HZ/suCoAd Groups | A participant seropositive for anti-gE antibodies is defined as a participant whose anti-gE antibody concentration was greater than or equal to the assay cut-off value (97 mIU/mL). | At pre-vaccination (Week 2 for HZ/suSeq group and Day 1 for HZ/suCoAd group) and at 1 month post-dose 2 of HZ/su vaccine administration (Week 14 for HZ/suSeq group and Week 12 for HZ/suCoAd group) | 
| Anti-gE Antibody Concentrations Expressed as GMCs in HZ/suSeq and HZ/suCoAd Groups | Anti-gE antibody concentrations were determined by ELISA and expressed as GMCs in mIU/mL. | At pre-vaccination (Week 2 for HZ/suSeq group and Day 1 for HZ/suCoAd group) and at 1 month post-dose 2 of HZ/su vaccine administration (Week 14 for HZ/suSeq group and Week 12 for HZ/suCoAd group) | 
| Percentage of Participants With a Vaccine Response for Anti-gE in HZ/suSeq and HZ/suCoAd Groups | A participant with vaccine response for anti-gE is defined as a participant with: At least a 4-fold greater post-dose anti-gE antibodies concentration as compared to the pre-vaccination anti-gE antibodies concentration, for participants who were seropositive at pre-vaccination, or, At least a 4-fold greater post-dose anti-gE antibodies concentration as compared to the anti-gE antibodies cut-off value for seropositivity, for participants who were seronegative at pre-vaccination. | At 1 month post-dose 2 of HZ/su vaccine administration (Week 14 for HZ/suSeq group and Week 12 for HZ/suCoAd group) | 
| Mean Geometric Increase (MGI) for Anti-gE in HZ/suSeq and HZ/suCoAd Groups | MGI is defined as the geometric mean of the within participant ratios of the post-vaccination anti-gE antibody concentration to the pre-vaccination anti-gE antibody concentration. | At 1 month post-dose 2 of HZ/su vaccine administration (Week 14 for HZ/suSeq group and Week 12 for HZ/suCoAd group) compared to pre-vaccination (Week 2 for HZ/suSeq group and Day 1 for HZ/suCoAd group) | 
| Anti-S Protein Antibody Concentrations Expressed as GMCs in HZ/suSeq and HZ/suCoAd Groups | Anti-S antibody concentrations were determined by Multiplex Electrochemiluminescence assay and expressed as GMCs in AU/mL. | At pre-vaccination (Day 1) and at 1 month post-mRNA-1273 booster dose administration (Week 4 for both HZ/suSeq and HZ/suCoAd groups) | 
| Anti-S Protein Antibody Concentrations Expressed as GMCs in FluD-QIVSeq and FluD-QIVCoAd Groups | Anti-S antibody concentrations were determined by Multiplex Electrochemiluminescence assay and expressed as GMCs in AU/mL. | At pre-vaccination (Day 1) and at 1 month post-mRNA-1273 booster dose administration (Week 4 for both FluD-QIVSeq and FluD-QIVCoAd groups) | 
| Mean Geometric Increase (MGI) for Anti-S Protein in HZ/suSeq and HZ/suCoAd Groups | MGI is defined as the geometric mean of the within participant ratios of the post-vaccination anti-S protein antibody concentration to the pre-vaccination anti-S protein antibody concentration. | At 1 month post-mRNA-1273 booster dose administration (Week 4 for both HZ/suSeq and HZ/suCoAd groups) compared to pre-vaccination (Day 1) | 
| Mean Geometric Increase (MGI) for Anti-S Protein in FluD-QIVSeq and FluD-QIVCoAd Groups | MGI is defined as the geometric mean of the within participant ratios of the post-vaccination anti-S protein antibody concentration to the pre-vaccination anti-S protein antibody concentration. | At 1 month post-mRNA-1273 booster dose administration (Week 4 for both FluD-QIVSeq and FluD-QIVCoAd groups) compared to pre-vaccination (Day 1) | 
| Anti-HI Antibody Titers Expressed as GMTs Against the 4 Influenza Strains in Flu D-QIV Vaccine in FluD-QIVSeq and FluD-QIVCoAd Groups | Antibody titers against the 4 influenza strains (A/H1N1 strain, A/H3N2 strain, B/Victoria lineage and B/Yamagata lineage) included in the FLU D-QIV vaccine were determined by hemagglutination inhibition and expressed as GMTs. | At pre-vaccination (Week 2 for FluD-QIVSeq group and Day 1 for FluD-QIVCoAd group) and at 1 month post-Flu D-QIV vaccine dose administration (Week 6 for FluD-QIVSeq group and Week 4 for FluD-QIVCoAd group) | 
| Percentage of Participants Seroprotected for Anti-HI Antibodies Against the 4 Influenza Strains in FluD-QIV Vaccine in FluD-QIVSeq and FluD-QIVCoAd Groups, Overall and by Age Category | A participant seroprotected for anti-HI antibodies against the 4 influenza strains included in the FluD-QIV vaccine is defined as a participant with a serum HI titer ≥ 1:40. The 4 influenza strains assessed were A/H1N1 strain, A/H3N2 strain, B/Victoria lineage and B/Yamagata lineage. The age categories assessed were 18-64 and ≥ 65 years of age (YOA). | At pre-vaccination (Week 2 for FluD-QIVSeq group and Day 1 for FluD-QIVCoAd group) and at 1 month post-Flu D-QIV vaccine dose administration (Week 6 for FluD-QIVSeq group and Week 4 for FluD-QIVCoAd group) | 
| Percentage of Participants Seropositive for Anti-HI Antibodies Against the 4 Influenza Strains in FluD-QIV Vaccine in FluD-QIVSeq and FluD-QIVCoAd Groups | A participant seropositive for anti-HI antibodies against the 4 influenza strains included in the FluD-QIV vaccine is defined as a participant with a serum HI titer ≥ 1:10. The 4 influenza strains assessed were A/H1N1 strain, A/H3N2 strain, B/Victoria lineage and B/Yamagata lineage. | At pre-vaccination (Week 2 for FluD-QIVSeq group and Day 1 for FluD-QIVCoAd group) and at 1 month post-Flu D-QIV vaccine dose administration (Week 6 for FluD-QIVSeq group and Week 4 for FluD-QIVCoAd group) | 
| Mean Geometric Increase (MGI) for Anti-HI Against the 4 Influenza Strains in FluD-QIV Vaccine in FluD-QIVSeq and FluD-QIVCoAd Groups | MGI is defined as the geometric mean of the within participant ratios of the post-vaccination reciprocal HI titer to the pre-vaccination reciprocal HI titer. The 4 influenza strains assessed were A/H1N1 strain, A/H3N2 strain, B/Victoria lineage and B/Yamagata lineage. | At 1 month post-Flu D-QIV vaccine dose administration (Week 6 for FluD-QIVSeq group and Week 4 for FluD-QIVCoAd group) compared to pre-vaccination (Week 2 for FluD-QIVSeq group and Day 1 for FluD-QIVCoAd group) | 
| Percentage of Participants Seroconverted for Anti-HI Antibodies Against the 4 Influenza Strains in FluD-QIV Vaccine in FluD-QIVSeq and FluD-QIVCoAd Groups, Overall and by Age Category | A participant seroconverted for anti-HI antibodies against the 4 influenza strains is defined as a participant having either a pre-vaccination HI titer < 1:10 and a post-vaccination HI titer ≥ 1:40, or a pre-vaccination HI titer ≥ 1:10 and at least a 4 fold greater post-vaccination HI titer. The 4 influenza strains assessed were A/H1N1 strain, A/H3N2 strain, B/Victoria lineage and B/Yamagata lineage. The age categories assessed were 18-64 and ≥65 years of age (YOA). | At 1 month post-Flu D-QIV vaccine dose administration (Week 6 for FluD-QIVSeq group and Week 4 for FluD-QIVCoAd group) compared to pre-vaccination (Week 2 for FluD-QIVSeq group and Day 1 for FluD-QIVCoAd group) | 
| Percentage of Participants in HZ/suSeq and HZ/suCoAd Groups Reporting Solicited Local Adverse Events (AEs) | The assessed solicited local AEs included axillary (underarm) swelling or tenderness, pain, pruritus, redness and swelling. Axillary swelling or tenderness was solicited for all participants and not restricted to mRNA-1273 recipients as was originally planned per protocol. Pruritus was solicited for all participants and not restricted to HZ/su recipients as was originally planned per protocol. | Within 7 days after each vaccine dose and across doses (vaccines administered at Day 1, Week 2 and Week 10 for HZ/suSeq group and at Day 1 and Week 8 for HZ/suCoAd group) | 
| Percentage of Participants in FluD-QIVSeq and FluD-QIVCoAd Groups Reporting Solicited Local Adverse Events (AEs) | The assessed solicited local AEs included axillary (underarm) swelling or tenderness, pain, pruritus, redness and swelling. Axillary swelling or tenderness was solicited for all participants and not restricted to mRNA-1273 recipients as was originally planned per protocol. Pruritus was solicited for all participants and not restricted to HZ/su recipients as was originally planned per protocol. | Within 7 days after each vaccine dose and across doses (vaccines administered at Day 1 and Week 2 for FluD-QIVSeq group and at Day 1 for FluD-QIVCoAd group) | 
| Percentage of Participants in HZ/suSeq and HZ/suCoAd Groups Reporting Solicited Systemic Adverse Events (AEs) | The assessed solicited systemic AEs included abdominal pain, arthralgia, chills, diarrhea, fatigue, fever, gastrointestinal symptoms, headache, myalgia, nausea and vomiting. Fever is defined as temperature ≥ 38.0 degrees Celsius (°C)/100.4 degrees Fahrenheit (°F) by any route. The preferred location for measuring temperature was the oral route. | Within 7 days after each vaccine dose and across doses (vaccines administered at Day 1, Week 2 and Week 10 for HZ/suSeq group and at Day 1 and Week 8 for HZ/suCoAd group) | 
| Percentage of Participants in FluD-QIVSeq and FluD-QIVCoAd Groups Reporting Solicited Systemic Adverse Events (AEs) | The assessed solicited systemic AEs included abdominal pain, arthralgia, chills, diarrhea, fatigue, fever, gastrointestinal symptoms, headache, myalgia, nausea and vomiting. Fever is defined as temperature ≥ 38.0°C/100.4°F by any route. The preferred location for measuring temperature was the oral route. | Within 7 days after each vaccine dose and across doses (vaccines administered at Day 1 and Week 2 for FluD-QIVSeq group and at Day 1 for FluD-QIVCoAd group) | 
| Percentage of Participants in HZ/suSeq and HZ/suCoAd Groups Reporting Unsolicited Adverse Events (AEs) | An unsolicited AE was defined as any AE that was either not included in the list of solicited events using a participant diary, or was included in the list of solicited events, but with an onset more than 7 days following administration of a study intervention. | Within 14 days after each vaccine dose and across doses (vaccines administered at Day 1, Week 2 and Week 10 for HZ/suSeq group and at Day 1 and Week 8 for HZ/suCoAd group) | 
| Percentage of Participants in FluD-QIVSeq and FluD-QIVCoAd Groups Reporting Unsolicited Adverse Events (AEs) | An unsolicited AE was defined as any AE that was either not included in the list of solicited events using a participant diary, or was included in the list of solicited events, but with an onset more than 7 days following administration of a study intervention. | Within 14 days after each vaccine dose and across doses (vaccines administered at Day 1 and Week 2 for FluD-QIVSeq group and at Day 1 for FluD-QIVCoAd group) | 
| Percentage of Participants in HZ/suSeq and HZ/suCoAd Groups Reporting Unsolicited Adverse Events (AEs) | An unsolicited AE was defined as any AE that was either not included in the list of solicited events using a participant diary, or was included in the list of solicited events, but with an onset more than 7 days following administration of a study intervention. | Within 30 days after each vaccine dose and across vaccine doses (vaccines administered at Day 1, Week 2 and Week 10 for HZ/suSeq group and at Day 1 and Week 8 for HZ/suCoAd group) | 
| Percentage of Participants in FluD-QIVSeq and FluD-QIVCoAd Groups Reporting Unsolicited Adverse Events (AEs) | An unsolicited AE was defined as any AE that was either not included in the list of solicited events using a participant diary, or was included in the list of solicited events, but with an onset more than 7 days following administration of a study intervention. | Within 30 days after each vaccine dose and across vaccine doses (vaccines administered at Day 1 and Week 2 for FluD-QIVSeq group and at Day 1 for FluD-QIVCoAd group) | 
| Percentage of Participants in HZ/suSeq and HZ/suCoAd Groups Reporting Serious Adverse Events (SAEs) | An SAE was defined as any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect in the offspring of a study participant, was considered or defined as an important medical event, or abnormal pregnancy outcomes. | From first vaccine dose (Day 1) up to 30 days post-last vaccine dose within each group | 
| Percentage of Participants in HZ/suSeq and HZ/suCoAd Groups Reporting Serious Adverse Events (SAEs) | An SAE was defined as any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect in the offspring of a study participant, was considered or defined as an important medical event, or abnormal pregnancy outcomes. | From first vaccine dose (Day 1) up to study end (24 weeks post-last vaccine dose) | 
| Percentage of Participants in FluD-QIVSeq and FluD-QIVCoAd Groups Reporting Serious Adverse Events (SAEs) | An SAE was defined as any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect in the offspring of a study participant, was considered or defined as an important medical event, or abnormal pregnancy outcomes. | From first vaccine dose (Day 1) up to 30 days post-last vaccine dose within each group | 
| Percentage of Participants in FluD-QIVSeq and FluD-QIVCoAd Groups Reporting Serious Adverse Events (SAEs) | An SAE was defined as any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect in the offspring of a study participant, was considered or defined as an important medical event, or abnormal pregnancy outcomes. | From first vaccine dose (Day 1) up to study end (24 weeks post-last vaccine dose) | 
| Percentage of Participants in HZ/suSeq and HZ/suCoAd Groups Reporting Potential Immune Mediated Diseases (pIMDs) | The assessed pIMDs included autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have had an autoimmune etiology. | From first vaccine dose (Day 1) up to 30 days post-last vaccine dose within each group | 
| Percentage of Participants in HZ/suSeq and HZ/suCoAd Groups Reporting Potential Immune Mediated Diseases (pIMDs) | The assessed pIMDs included autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have had an autoimmune etiology. | From first vaccine dose (Day 1) up to study end (24 weeks post-last vaccine dose) | 
| Percentage of Participants in HZ/suSeq and HZ/suCoAd Groups Reporting Adverse Events of Special Interest (AESIs) | AESIs were defined as medical concepts that may have been related to COVID-19 or were of interest in COVID-19 vaccine safety surveillance. | From first vaccine dose (Day 1) up to 30 days post-last vaccine dose within each group | 
| Percentage of Participants in HZ/suSeq and HZ/suCoAd Groups Reporting Adverse Events of Special Interest (AESIs) | AESIs were defined as medical concepts that may have been related to COVID-19 or were of interest in COVID-19 vaccine safety surveillance. | From first vaccine dose (Day 1) up to study end (24 weeks post-last vaccine dose) | 
| Percentage of Participants in FluD-QIVSeq and FluD-QIVCoAd Groups Reporting Adverse Events of Special Interest (AESIs) | AESIs were defined as medical concepts that may have been related to COVID-19 or were of interest in COVID-19 vaccine safety surveillance. | From first vaccine dose (Day 1) up to 30 days post-last vaccine dose within each group | 
| Percentage of Participants in FluD-QIVSeq and FluD-QIVCoAd Groups Reporting Adverse Events of Special Interest (AESIs) | AESIs were defined as medical concepts that may have been related to COVID-19 or were of interest in COVID-19 vaccine safety surveillance. | From first vaccine dose (Day 1) up to study end (24 weeks post-last vaccine dose) | 
| Percentage of Participants in HZ/suSeq and HZ/suCoAd Groups Reporting Clinically Suspected HZ Episodes | A suspected HZ episode is defined as a new unilateral rash accompanied by pain broadly defined to include allodynia, pruritus or other sensations without alternative diagnosis. | From first vaccine dose (Day 1) up to study end (24 weeks post-last vaccine dose) | 
| Percentage of Participants in HZ/suSeq and HZ/suCoAd Groups Meeting Case Definitions of COVID-19 | Primary Case Definition: Experienced at least TWO of following systemic symptoms: fever (temperature ≥38ºC), chills, myalgia, headache, sore throat, new olfactory & taste disorder(s), OR at least ONE of following respiratory signs: cough, shortness of breath or difficulty breathing, OR clinical or radiographical evidence of pneumonia; AND must have at least one nasopharyngeal (NP) or nasal swab, or saliva or respiratory sample positive for SARS-CoV-2 by PCR. Secondary Case Definition: Following systemic symptoms: fever, or chills, cough, shortness of breath or difficulty breathing, fatigue, muscle aches or body aches, headache, new loss of taste or smell, sore throat, nasal congestion or rhinorrhea, nausea or vomiting, or diarrhea AND a positive NP or nasal swab, or saliva or respiratory sample for SARS-CoV-2 by PCR. Tertiary Case Definition: Documented COVID-19 diagnosis made by health care provider and not meeting the above case definitions. | From first vaccine dose (Day 1) up to study end (24 weeks post-last vaccine dose) | 
| Percentage of Participants in FluD-QIVSeq and FluD-QIVCoAd Groups Meeting Case Definitions of COVID-19 | Primary Case Definition: Experienced at least TWO of following systemic symptoms: fever (temperature ≥38ºC), chills, myalgia, headache, sore throat, new olfactory & taste disorder(s), OR at least ONE of following respiratory signs: cough, shortness of breath or difficulty breathing, OR clinical or radiographical evidence of pneumonia; AND must have at least one nasopharyngeal (NP) or nasal swab, or saliva or respiratory sample positive for SARS-CoV-2 by PCR. Secondary Case Definition: Following systemic symptoms: fever, or chills, cough, shortness of breath or difficulty breathing, fatigue, muscle aches or body aches, headache, new loss of taste or smell, sore throat, nasal congestion or rhinorrhea, nausea or vomiting, or diarrhea AND a positive NP or nasal swab, or saliva or respiratory sample for SARS-CoV-2 by PCR. Tertiary Case Definition: Documented COVID-19 diagnosis made by health care provider and not meeting the above case definitions. | From first vaccine dose (Day 1) up to study end (24 weeks post-last vaccine dose) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Shingles, Influenza, Booster vaccination, HZ/su vaccine, Recombinant Zoster vaccine, Flu D-QIV vaccine, mRNA-1273 vaccine, Immunogenicity, Safety, COVID-19