COVID-19
Conditions
Keywords
Booster dose Moderna and Novavax, control group, monovalent, bivalent
Brief summary
This is a double-blinded, randomised study to determine the safety, reactogenicity, and immunogenicity of a bivalent mRNA Moderna COVID-19 vaccine or a protein-based Novavax COVID-19 vaccine given as a fourth dose in healthy adults in Australia.
Detailed description
This is a blinded, two-arm randomised study to determine the safety, reactogenicity and immunogenicity of a fourth dose of SARS-CoV-2 vaccines in Australia in adults 18 years or older who have received their third dose of COVID-19 vaccine at least six months previously. Participants will be randomised to receive either bivalent Moderna (mRNA-1273.214) or Novavax. A separate non-randomised control arm (no vaccine given), frequency matched by age to the vaccine groups will also be enrolled for comparison. A total of 200 participants per group will be recruited.
Interventions
BIOLOGICALBivalent Moderna
A single standard dose of the bivalent Moderna (mRNA-1273.214) COVID-19 vaccine containing equal amounts of mRNAs (25μg of each mRNA sequence) that encode the prefusion stabilized spike glycoproteins of the ancestral SARS-CoV-2 (Wuhan-Hu-1) and the Omicron variant (B.1.1.529 \[BA.1\]) with mRNAs encapsulated in lipid nanoparticles, will be administered on day 0 of the study.
BIOLOGICALNovavax
A single dose of Novavax contains 5μg of SARS-CoV-2 spike protein and is adjuvanted with Matrix-M. Adjuvant Matrix-M contains, per 0.5 mL dose: Quillaja saponaria saponins fraction A (42.5 micrograms) and Quillaja saponaria saponins fraction C (7.5 micrograms), will be administered on day 0 of the study.
Sponsors
Coalition for Epidemic Preparedness Innovations
The Peter Doherty Institute for Infection and Immunity
Murdoch Childrens Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Masking description
The participants and those evaluating reactogenicity will be blinded to the vaccine allocation for the first 7 days following vaccination. After that, both clinical investigators and participants will be aware of their investigational product. Laboratory staff will remain blinded to the investigational product.
Intervention model description
Study participants who have previously received 3 COVID-19 vaccines will be either randomised into one of two vaccine groups or be part of a self-selected control group. Randomised participants will receive a standard dose of either the bivalent Moderna or the protein-based Novavax vaccine. 200 non-randomised participants will be part of a control group and will not receive any COVID-19 vaccine.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Have received three doses of COVID-19 vaccines at least 6 months earlier. 2. No confirmed SARS-CoV-2 infection on PCR or RAT within the last 3 months. 3. Willing and able to give written informed consent. 4. Aged 18 years or above. 5. Willing to complete the follow-up requirements of the study.
Exclusion criteria
1. Currently receiving immunosuppressive medication or anti-cancer chemotherapy. 2. Known HIV infection. 3. Congenital immune deficiency syndrome. 4. Received immunoglobulin or other blood products in the three months prior to potential study booster vaccination. 5. Study staff and their relatives. 6. Have a history of a severe allergic reaction to any COVID-19 vaccines or have a medical exemption to receiving further COVID-19 vaccines. 7. Cannot read or understand English.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Incidence of Solicited Reactions (Systemic and Local) | Total incidence of solicited reactions will be measured for 7 days post booster vaccination | Questionnaire to document solicited reactions is developed specifically for this study. Data will be reported as the proportion of participants who report by each intervention arm. Solicited reactions such as pain, tenderness, erythema/redness, induration/swelling, fever, nausea/vomiting, headache, fatigue/malaise, myalgia, arthralgia will be collected from the participants 7 days post-vaccination. Reactogenicity was graded on a 0-4 scale: Grade 0 = no symptom; Grade 1 = mild and does not interfere with activity; Grade 2 = moderate or requiring repeated non-narcotic analgesia; Grade 3 = severe, limiting or preventing daily activity; Grade 4 = potentially life-threatening, requiring ER visit or hospitalisation. |
| SARS-CoV-2 Specific Immunoglobulin (Ig)G Antibodies at 28-days Post Booster Vaccination | 28-days post booster vaccination | Serum samples collected at 28-days post booster vaccination from the two intervention groups will be evaluated for SARS-CoV-2 specific IgG antibodies using the commercial Euroimmun S1 IgG ELISA. Data will be reported as binding antibody units/mL and presented as geometric mean concentration and 95% confidence intervals |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| SARS-CoV-2 Specific Neutralising Antibodies Measured by Surrogate Virus Neutralization Test (sVNT) | Baseline (pre booster), 28 days, 6,12, 18, 24, and 30 months post booster vaccination | Neutralising antibody levels will be measured using the GenScript® cPass sVNT, which reports inhibition relative to a positive control. Results are expressed as concentrations (U/mL) and summarised as geometric mean concentrations (GMCs) with 95% CIs. |
| SARS-CoV-2 Specific Neutralising Antibodies at Baseline (Pre Booster), 28 Days and 6, 12 and 18 Months Post Booster Vaccination Measured by SARS-CoV-2 Microneutralisation Assay | Baseline (pre booster), 6,12 and 18-months post booster vaccination | A subset of samples (20%) from all timepoints will be assessed using a SARS-CoV-2 microneutralisation assay to both the wild type (vaccine) strain and for two SARS-CoV-2 Variants of concern. Neutralizing antibody will be reported as endpoint titre. |
| Interferon Gamma (IFNγ) Concentrations in International Units (IU)/mL | Baseline (pre booster), Day 28, 6-months and 12-months post booster vaccination | Interferon gamma (IFNγ) concentrations as a measurement of cellular immunity will be assessed on a subset (50%) of the participants from each group. QuantiFERON Human IFN-γ SARS-CoV-2 (Qiagen) will be used to stimulate IFN-γ production in whole blood and then IFN-γ production will be measured using Enzyme-Linked ImmunoSorbent Assay (ELISA). Data will be presented as geometric mean concentration (GMC) and 95% confidence intervals (CI). |
| Number of IFNγ Producing Cells/Million PBMCs | Baseline (pre booster), 6, 12 and 18-months post booster vaccination | IFNγ producing cells as a measurement of cellular immunity will be assessed on a subset (50%) of the participants from each group. IFN-γ Enzyme-Linked ImmunoSpot (Elispot) assay will be performed on isolated peripheral blood mononuclear cells (PBMCs) stimulated with SARS-CoV-2 specific peptides. Data will be reported as number of IFNγ producing cells/million and presented using means and 95% confidence intervals. |
| Cytokine Concentrations Following PBMCs Stimulation | Baseline (pre booster), 6, 12 and 18-months post booster vaccination | Cytokine concentrations following PBMCs stimulation will be assessed on a subset (50%) of participants using multiplex cytokine assays. Data will be reported as cytokine concentrations in pg/ml and presented as GMC and 95% CI. |
| Incidence of Unsolicited Adverse Events (AE) | 28 days-post booster vaccination | Unsolicited adverse events were collected for 28 days post-booster. Results are reported as the number and percentage of randomised participants in each arm who experienced an unsolicited AE. |
| Incidence of Medically Attended Adverse Events (AE) | 3 months post booster vaccination | Participants with medically attended AE will be collected for 3 months post booster vaccination. Data will be presented as number of medically attended adverse events. Serious adverse events (SAEs) are reported separately. |
| Incidence of Serious Adverse Events (SAE) | 24 months post booster vaccination | Serious adverse events (SAEs) were collected throughout the 24-month follow-up period after booster vaccination. Data are reported as the number of SAEs occurring in each randomised arm. |
| Frequency of Cytokine-expressing T Cells | Baseline (pre booster), 6, 12 and 18 -months post booster vaccination | Frequency of cytokine-expressing T cells will be assessed on a subset (50%) of participants using Flow cytometry (intracellular staining) on PBMCs samples stimulated with SARS-CoV-2 specific peptides. Data will be reported as frequency (%) of cytokine-expressing T cells presented as means and 95% CI. |
| SARS-CoV-2 Specific IgG Antibodies at Baseline (Pre Booster), and 6,12 and 18 Months Post Booster Vaccination | Baseline (pre booster), 6-months,12-months and 18-months post booster vaccination | Serum samples collected at baseline (pre booster), 28 days, 6,12, 18, 24, and 30 months post booster vaccination from the two intervention groups and the control group will be evaluated for SARS-CoV-2 specific IgG antibodies using the commercial Euroimmun S1 IgG ELISA . Data will be reported as binding antibody units/mL and presented as geometric mean concentration and 95% confidence intervals |
Other
| Measure | Time frame | Description |
|---|---|---|
| SARS-CoV-2 Infections | 24 months post booster vaccination | SARS-CoV-2 infections were recorded throughout the 24-month follow-up period based on participant self-report of a positive RAT or PCR test. Data are reported as the number of infections occurring in each study arm during this period |
Countries
Australia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bivalent Moderna (mRNA-1273.214) Participants who have received three doses of COVID-19 vaccine, with the last dose at least 6 months prior to the study, will receive a booster dose of bivalent mRNA Moderna COVID-19 vaccine (mRNA-1273.214)
The mRNA-1273.214 encodes the prefusion stabilized S protein of SARS-CoV-2 formulated in RNA-lipid nanoparticles composed of 4 lipids and 1-monomethoxypolyethyleneglycol-2, 3-dimyristylglycerol with polyethylene glycol. 25μg of each mRNA sequence that encode the prefusion stabilized spike glycoproteins of the ancestral SARS-CoV-2 (Wuhan-Hu-1) and the Omicron variant (B.1.1.529 \[BA.1\]).
Bivalent Moderna: A single standard dose of the bivalent Moderna (mRNA-1273.214) COVID-19 vaccine containing equal amounts of mRNAs (25μg of each mRNA sequence) that encode the prefusion stabilized spike glycoproteins of the ancestral SARS-CoV-2 (Wuhan-Hu-1) and the Omicron variant (B.1.1.529 \[BA.1\]) with mRNAs encapsulated in lipid nanoparticles, will be administered on day 0 of the study. | 177 |
| Novavax Participants who have received three doses of COVID-19 vaccine, with the last dose at least 6 months prior to the study, will receive a booster dose of Novavax COVID-19 protein subunit vaccine.
Novavax contains 5μg of SARS-CoV-2 spike protein and is adjuvanted with Matrix-M. Adjuvant Matrix-M contains, per 0.5 mL dose: Quillaja saponaria saponins fraction A (42.5 micrograms) and Quillaja saponaria saponins fraction C (7.5 micrograms).
Novavax: A single dose of Novavax contains 5μg of SARS-CoV-2 spike protein and is adjuvanted with Matrix-M. Adjuvant Matrix-M contains, per 0.5 mL dose: Quillaja saponaria saponins fraction A (42.5 micrograms) and Quillaja saponaria saponins fraction C (7.5 micrograms), will be administered on day 0 of the study. | 176 |
| Control Group- no Vaccine Participants who have received three doses of COVID-19 vaccine, with the last dose at least 6 months prior to the study, will be recruited but will not receive any COVID-19 vaccine. | 143 |
| Total | 496 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| 12 Months | Lost to Follow-up | 2 | 6 | 3 |
| 12 Months | Visit missed | 4 | 8 | 8 |
| 12 Months | Withdrawal by Subject | 4 | 4 | 2 |
| 18 Months | Lost to Follow-up | 5 | 8 | 2 |
| 18 Months | Visit missed | 12 | 14 | 6 |
| 18 Months | Withdrawal by Subject | 17 | 9 | 16 |
| 28 Days | Lost to Follow-up | 1 | 0 | 0 |
| 28 Days | Visit missed | 0 | 4 | 0 |
| 28 Days | Withdrawal by Subject | 1 | 1 | 0 |
| 6 Months | Lost to Follow-up | 1 | 7 | 2 |
| 6 Months | No blood draw | 0 | 0 | 1 |
| 6 Months | Visit missed | 5 | 7 | 0 |
| 6 Months | Withdrawal by Subject | 1 | 3 | 4 |
| Baseline | No blood draw | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Novavax | Total | Bivalent Moderna (mRNA-1273.214) | Control Group- no Vaccine |
|---|---|---|---|---|
| Age, Continuous | 31 years | 32 years | 30 years | 39 years |
| Age, Customized ≥18 to <50 years | 150 Participants | 401 Participants | 150 Participants | 101 Participants |
| Age, Customized ≥50 years | 26 Participants | 95 Participants | 27 Participants | 42 Participants |
| BMI | 24.8 kg/m^2 | 24.5 kg/m^2 | 24.7 kg/m^2 | 24.2 kg/m^2 |
| Comorbidities Asthma | 28 Participants | 72 Participants | 25 Participants | 19 Participants |
| Comorbidities Cancer | 0 Participants | 2 Participants | 2 Participants | 0 Participants |
| Comorbidities Cardiovascular disease | 3 Participants | 5 Participants | 1 Participants | 1 Participants |
| Comorbidities Chronic kidney disease | 0 Participants | 2 Participants | 1 Participants | 1 Participants |
| Comorbidities Chronic liver disease | 0 Participants | 3 Participants | 1 Participants | 2 Participants |
| Comorbidities Chronic obstructive pulmonary disease | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Comorbidities Cigarette user | 7 Participants | 12 Participants | 5 Participants | 0 Participants |
| Comorbidities Diabetes mellitus | 4 Participants | 11 Participants | 4 Participants | 3 Participants |
| Comorbidities Gestational diabetes | 1 Participants | 2 Participants | 0 Participants | 1 Participants |
| Comorbidities History of anaphylaxis | 2 Participants | 7 Participants | 3 Participants | 2 Participants |
| Comorbidities History of mastocytosis | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Comorbidities Hypertension | 9 Participants | 25 Participants | 8 Participants | 8 Participants |
| Comorbidities Neurological disease | 2 Participants | 4 Participants | 1 Participants | 1 Participants |
| Comorbidities Obesity (BMI ≥30 kg/m^2) | 33 Participants | 81 Participants | 27 Participants | 21 Participants |
| Comorbidities On anticoagulant therapy | 2 Participants | 8 Participants | 2 Participants | 4 Participants |
| Comorbidities Pregnant at time of enrolment | 1 Participants | 3 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 3 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 172 Participants | 489 Participants | 175 Participants | 142 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 4 Participants | 2 Participants | 0 Participants |
| Number of times tested positive for SARS-CoV-2 0 prior positive SARS-CoV-2 tests | 30 Participants | 109 Participants | 37 Participants | 42 Participants |
| Number of times tested positive for SARS-CoV-2 1 prior positive SARS-CoV-2 tests | 113 Participants | 291 Participants | 109 Participants | 69 Participants |
| Number of times tested positive for SARS-CoV-2 2 prior positive SARS-CoV-2 tests | 28 Participants | 82 Participants | 26 Participants | 28 Participants |
| Number of times tested positive for SARS-CoV-2 3 prior positive SARS-CoV-2 tests | 4 Participants | 13 Participants | 5 Participants | 4 Participants |
| Number of times tested positive for SARS-CoV-2 4 prior positive SARS-CoV-2 tests | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 3 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 33 Participants | 132 Participants | 41 Participants | 58 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 3 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 4 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) White | 139 Participants | 352 Participants | 129 Participants | 84 Participants |
| Region of Enrollment Australia | 176 Participants | 496 Participants | 177 Participants | 143 Participants |
| Sex: Female, Male Female | 128 Participants | 358 Participants | 116 Participants | 114 Participants |
| Sex: Female, Male Male | 48 Participants | 138 Participants | 61 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 177 | 0 / 176 | 0 / 143 |
| other Total, other adverse events | 10 / 177 | 8 / 176 | 1 / 143 |
| serious Total, serious adverse events | 5 / 177 | 8 / 176 | 8 / 143 |
Outcome results
Primary
SARS-CoV-2 Specific Immunoglobulin (Ig)G Antibodies at 28-days Post Booster Vaccination
Serum samples collected at 28-days post booster vaccination from the two intervention groups will be evaluated for SARS-CoV-2 specific IgG antibodies using the commercial Euroimmun S1 IgG ELISA. Data will be reported as binding antibody units/mL and presented as geometric mean concentration and 95% confidence intervals
Time frame: 28-days post booster vaccination
Population: Moderna group:By day 28 1 participant was lost to follow-up and 1 had withdrawn Novavax: 4 people missed their visit for the day 28 blood draw and 1 was a withdrawal.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Bivalent Moderna (mRNA-1273.214) | SARS-CoV-2 Specific Immunoglobulin (Ig)G Antibodies at 28-days Post Booster Vaccination | 6792 binding antibody units (BAU/mL) |
| Novavax | SARS-CoV-2 Specific Immunoglobulin (Ig)G Antibodies at 28-days Post Booster Vaccination | 3179 binding antibody units (BAU/mL) |
Primary
Total Incidence of Solicited Reactions (Systemic and Local)
Questionnaire to document solicited reactions is developed specifically for this study. Data will be reported as the proportion of participants who report by each intervention arm. Solicited reactions such as pain, tenderness, erythema/redness, induration/swelling, fever, nausea/vomiting, headache, fatigue/malaise, myalgia, arthralgia will be collected from the participants 7 days post-vaccination. Reactogenicity was graded on a 0-4 scale: Grade 0 = no symptom; Grade 1 = mild and does not interfere with activity; Grade 2 = moderate or requiring repeated non-narcotic analgesia; Grade 3 = severe, limiting or preventing daily activity; Grade 4 = potentially life-threatening, requiring ER visit or hospitalisation.
Time frame: Total incidence of solicited reactions will be measured for 7 days post booster vaccination
Population: Solicited local and systemic reactions were collected for 7 days post-vaccination using a study-specific questionnaire. Outcomes are reported as both the number of participants in each arm and the percentage of participants in that arm experiencing reactions by severity grade. Reactions were graded on a 0-4 scale: Grade 0 = no symptom; Grade 1 = mild (does not interfere with activity); Grade 2 = moderate (may require non-narcotic analgesia); Grade 3 = severe (limits or prevents daily activity);
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Headache | Grade 1 (Mild) | 61 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Pain | Grade 1 (Mild) | 105 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Pain | Grade 2 Moderate | 19 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Swelling | Grade 3 Severe | 1 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Pain | Grade 3 Severe | 0 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Pain | Grade 4 Potentially Life Threatening | 0 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Tenderness | Grade 0 no symptoms | 33 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Tenderness | Grade 1 (Mild) | 80 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Tenderness | Grade 2 Moderate | 60 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Tenderness | Grade 3 Severe | 4 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Tenderness | Grade 4 Potentially Life Threatening | 0 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Redness | Grade 0 no symptoms | 164 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Redness | Grade 1 (Mild) | 6 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Redness | Grade 2 Moderate | 5 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Redness | Grade 3 Severe | 1 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Redness | Grade 4 Potentially Life Threatening | 1 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Swelling | Grade 0 no symptoms | 157 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Swelling | Grade 1 (Mild) | 9 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Swelling | Grade 2 Moderate | 9 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Swelling | Grade 4 Potentially Life Threatening | 1 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Hard | Grade 0 no symptoms | 157 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Hard | Grade 1 (Mild) | 14 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Hard | Grade 2 Moderate | 5 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Hard | Grade 3 Severe | 0 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Hard | Grade 4 Potentially Life Threatening | 1 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Axillary Lymphadenopathy | Grade 0 no symptoms | 149 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Axillary Lymphadenopathy | Grade 1 (Mild) | 21 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Axillary Lymphadenopathy | Grade 2 Moderate | 7 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Axillary Lymphadenopathy | Grade 3 Severe | 0 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Axillary Lymphadenopathy | Grade 4 Potentially Life Threatening | 0 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Warmth | Grade 0 no symptoms | 119 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Warmth | Grade 1 (Mild) | 55 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Warmth | Grade 2 Moderate | 3 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Warmth | Grade 3 Severe | 0 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Warmth | Grade 4 Potentially Life Threatening | 0 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Itch | Grade 0 no symptoms | 160 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Itch | Grade 1 (Mild) | 17 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Itch | Grade 2 Moderate | 0 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Itch | Grade 3 Severe | 0 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Itch | Grade 4 Potentially Life Threatening | 0 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Fever | Grade 0 no symptoms | 173 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Fever | Grade 1 (Mild) | 3 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Fever | Grade 2 Moderate | 1 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Fever | Grade 3 Severe | 0 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Fever | Grade 4 Potentially Life Threatening | 0 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Nausea | Grade 0 no symptoms | 147 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Nausea | Grade 1 (Mild) | 24 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Nausea | Grade 2 Moderate | 6 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Nausea | Grade 3 Severe | 0 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Nausea | Grade 4 Potentially Life Threatening | 0 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Vomiting | Grade 0 no symptoms | 173 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Vomiting | Grade 1 (Mild) | 4 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Vomiting | Grade 2 Moderate | 0 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Vomiting | Grade 3 Severe | 0 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Vomiting | Grade 4 Potentially Life Threatening | 0 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Diarrhoea | Grade 0 no symptoms | 163 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Diarrhoea | Grade 1 (Mild) | 12 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Diarrhoea | Grade 2 Moderate | 2 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Diarrhoea | Grade 3 Severe | 0 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Diarrhoea | Grade 4 Potentially Life Threatening | 0 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Headache | Grade 0 no symptoms | 81 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Pain | Grade 0 no symptoms | 53 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Headache | Grade 2 Moderate | 35 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Headache | Grade 3 Severe | 0 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Headache | Grade 4 Potentially Life Threatening | 0 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Fatigue/Malaise | Grade 0 no symptoms | 76 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Fatigue/Malaise | Grade 2 Moderate | 42 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Fatigue/Malaise | Grade 3 Severe | 5 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Fatigue/Malaise | Grade 4 Potentially Life Threatening | 0 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Muscle pain | Grade 0 no symptoms | 94 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Muscle pain | Grade 1 (Mild) | 63 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Muscle pain | Grade 2 Moderate | 19 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Muscle pain | Grade 3 Severe | 1 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Muscle pain | Grade 4 Potentially Life Threatening | 0 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Joint pain | Grade 0 no symptoms | 128 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Joint pain | Grade 1 (Mild) | 36 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Joint pain | Grade 2 Moderate | 12 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Joint pain | Grade 3 Severe | 1 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Joint pain | Grade 4 Potentially Life Threatening | 0 Participants |
| Bivalent Moderna (mRNA-1273.214) | Total Incidence of Solicited Reactions (Systemic and Local) | Fatigue/Malaise | Grade 1 (Mild) | 54 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Tenderness | Grade 0 no symptoms | 86 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Fever | Grade 1 (Mild) | 1 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Pain | Grade 1 (Mild) | 61 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Headache | Grade 2 Moderate | 8 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Fever | Grade 2 Moderate | 0 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Pain | Grade 2 Moderate | 2 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Muscle pain | Grade 3 Severe | 1 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Pain | Grade 3 Severe | 0 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Fever | Grade 3 Severe | 2 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Pain | Grade 4 Potentially Life Threatening | 0 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Headache | Grade 3 Severe | 1 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Fever | Grade 4 Potentially Life Threatening | 1 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Tenderness | Grade 1 (Mild) | 72 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Joint pain | Grade 3 Severe | 0 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Tenderness | Grade 2 Moderate | 16 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Nausea | Grade 0 no symptoms | 159 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Tenderness | Grade 3 Severe | 2 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Headache | Grade 4 Potentially Life Threatening | 0 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Tenderness | Grade 4 Potentially Life Threatening | 0 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Nausea | Grade 1 (Mild) | 14 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Redness | Grade 0 no symptoms | 167 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Muscle pain | Grade 4 Potentially Life Threatening | 0 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Redness | Grade 1 (Mild) | 6 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Nausea | Grade 2 Moderate | 3 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Redness | Grade 2 Moderate | 3 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Fatigue/Malaise | Grade 0 no symptoms | 106 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Redness | Grade 3 Severe | 0 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Nausea | Grade 3 Severe | 0 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Redness | Grade 4 Potentially Life Threatening | 0 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Fatigue/Malaise | Grade 1 (Mild) | 44 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Swelling | Grade 0 no symptoms | 172 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Nausea | Grade 4 Potentially Life Threatening | 0 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Swelling | Grade 1 (Mild) | 3 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Vomiting | Grade 4 Potentially Life Threatening | 0 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Swelling | Grade 2 Moderate | 1 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Swelling | Grade 3 Severe | 0 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Vomiting | Grade 0 no symptoms | 174 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Swelling | Grade 4 Potentially Life Threatening | 0 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Fatigue/Malaise | Grade 2 Moderate | 22 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Hard | Grade 0 no symptoms | 171 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Vomiting | Grade 1 (Mild) | 2 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Hard | Grade 1 (Mild) | 4 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Joint pain | Grade 0 no symptoms | 157 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Hard | Grade 2 Moderate | 1 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Vomiting | Grade 2 Moderate | 0 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Hard | Grade 3 Severe | 0 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Fatigue/Malaise | Grade 3 Severe | 4 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Hard | Grade 4 Potentially Life Threatening | 0 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Vomiting | Grade 3 Severe | 0 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Axillary Lymphadenopathy | Grade 0 no symptoms | 162 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Joint pain | Grade 4 Potentially Life Threatening | 0 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Axillary Lymphadenopathy | Grade 1 (Mild) | 13 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Fatigue/Malaise | Grade 4 Potentially Life Threatening | 0 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Axillary Lymphadenopathy | Grade 2 Moderate | 1 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Diarrhoea | Grade 0 no symptoms | 163 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Axillary Lymphadenopathy | Grade 3 Severe | 0 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Joint pain | Grade 1 (Mild) | 16 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Axillary Lymphadenopathy | Grade 4 Potentially Life Threatening | 0 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Diarrhoea | Grade 1 (Mild) | 11 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Warmth | Grade 0 no symptoms | 146 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Muscle pain | Grade 0 no symptoms | 140 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Warmth | Grade 1 (Mild) | 29 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Diarrhoea | Grade 2 Moderate | 2 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Warmth | Grade 2 Moderate | 1 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Pain | Grade 0 no symptoms | 113 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Warmth | Grade 3 Severe | 0 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Diarrhoea | Grade 3 Severe | 0 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Warmth | Grade 4 Potentially Life Threatening | 0 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Muscle pain | Grade 1 (Mild) | 31 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Itch | Grade 0 no symptoms | 170 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Diarrhoea | Grade 4 Potentially Life Threatening | 0 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Itch | Grade 1 (Mild) | 4 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Joint pain | Grade 2 Moderate | 3 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Itch | Grade 2 Moderate | 2 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Headache | Grade 0 no symptoms | 127 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Itch | Grade 3 Severe | 0 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Muscle pain | Grade 2 Moderate | 4 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Itch | Grade 4 Potentially Life Threatening | 0 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Headache | Grade 1 (Mild) | 40 Participants |
| Novavax | Total Incidence of Solicited Reactions (Systemic and Local) | Fever | Grade 0 no symptoms | 172 Participants |
Secondary
Cytokine Concentrations Following PBMCs Stimulation
Cytokine concentrations following PBMCs stimulation will be assessed on a subset (50%) of participants using multiplex cytokine assays. Data will be reported as cytokine concentrations in pg/ml and presented as GMC and 95% CI.
Time frame: Baseline (pre booster), 6, 12 and 18-months post booster vaccination
Secondary
Frequency of Cytokine-expressing T Cells
Frequency of cytokine-expressing T cells will be assessed on a subset (50%) of participants using Flow cytometry (intracellular staining) on PBMCs samples stimulated with SARS-CoV-2 specific peptides. Data will be reported as frequency (%) of cytokine-expressing T cells presented as means and 95% CI.
Time frame: Baseline (pre booster), 6, 12 and 18 -months post booster vaccination
Secondary
Incidence of Medically Attended Adverse Events (AE)
Participants with medically attended AE will be collected for 3 months post booster vaccination. Data will be presented as number of medically attended adverse events. Serious adverse events (SAEs) are reported separately.
Time frame: 3 months post booster vaccination
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bivalent Moderna (mRNA-1273.214) | Incidence of Medically Attended Adverse Events (AE) | 0 Medically attended adverse events |
| Novavax | Incidence of Medically Attended Adverse Events (AE) | 1 Medically attended adverse events |
| Control Group- no Vaccine | Incidence of Medically Attended Adverse Events (AE) | 0 Medically attended adverse events |
Secondary
Incidence of Serious Adverse Events (SAE)
Serious adverse events (SAEs) were collected throughout the 24-month follow-up period after booster vaccination. Data are reported as the number of SAEs occurring in each randomised arm.
Time frame: 24 months post booster vaccination
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bivalent Moderna (mRNA-1273.214) | Incidence of Serious Adverse Events (SAE) | 5 Serious adverse events |
| Novavax | Incidence of Serious Adverse Events (SAE) | 8 Serious adverse events |
| Control Group- no Vaccine | Incidence of Serious Adverse Events (SAE) | 8 Serious adverse events |
Secondary
Incidence of Unsolicited Adverse Events (AE)
Unsolicited adverse events were collected for 28 days post-booster. Results are reported as the number and percentage of randomised participants in each arm who experienced an unsolicited AE.
Time frame: 28 days-post booster vaccination
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Bivalent Moderna (mRNA-1273.214) | Incidence of Unsolicited Adverse Events (AE) | Supraventricular tachycardia | 1 Participants |
| Bivalent Moderna (mRNA-1273.214) | Incidence of Unsolicited Adverse Events (AE) | Acne | 1 Participants |
| Bivalent Moderna (mRNA-1273.214) | Incidence of Unsolicited Adverse Events (AE) | Mouth ulceration | 1 Participants |
| Bivalent Moderna (mRNA-1273.214) | Incidence of Unsolicited Adverse Events (AE) | Heavy menstrual bleeding | 0 Participants |
| Bivalent Moderna (mRNA-1273.214) | Incidence of Unsolicited Adverse Events (AE) | Nasal congestion | 0 Participants |
| Bivalent Moderna (mRNA-1273.214) | Incidence of Unsolicited Adverse Events (AE) | Dyspnoea | 3 Participants |
| Bivalent Moderna (mRNA-1273.214) | Incidence of Unsolicited Adverse Events (AE) | Chest pain | 2 Participants |
| Bivalent Moderna (mRNA-1273.214) | Incidence of Unsolicited Adverse Events (AE) | Headache | 1 Participants |
| Bivalent Moderna (mRNA-1273.214) | Incidence of Unsolicited Adverse Events (AE) | Administration site pain | 0 Participants |
| Bivalent Moderna (mRNA-1273.214) | Incidence of Unsolicited Adverse Events (AE) | Road traffic accident | 0 Participants |
| Bivalent Moderna (mRNA-1273.214) | Incidence of Unsolicited Adverse Events (AE) | Tinnitus | 0 Participants |
| Bivalent Moderna (mRNA-1273.214) | Incidence of Unsolicited Adverse Events (AE) | No reported AE | 168 Participants |
| Novavax | Incidence of Unsolicited Adverse Events (AE) | Tinnitus | 1 Participants |
| Novavax | Incidence of Unsolicited Adverse Events (AE) | Supraventricular tachycardia | 0 Participants |
| Novavax | Incidence of Unsolicited Adverse Events (AE) | Chest pain | 1 Participants |
| Novavax | Incidence of Unsolicited Adverse Events (AE) | Acne | 0 Participants |
| Novavax | Incidence of Unsolicited Adverse Events (AE) | Road traffic accident | 2 Participants |
| Novavax | Incidence of Unsolicited Adverse Events (AE) | Mouth ulceration | 0 Participants |
| Novavax | Incidence of Unsolicited Adverse Events (AE) | Headache | 0 Participants |
| Novavax | Incidence of Unsolicited Adverse Events (AE) | Heavy menstrual bleeding | 1 Participants |
| Novavax | Incidence of Unsolicited Adverse Events (AE) | No reported AE | 168 Participants |
| Novavax | Incidence of Unsolicited Adverse Events (AE) | Nasal congestion | 1 Participants |
| Novavax | Incidence of Unsolicited Adverse Events (AE) | Administration site pain | 1 Participants |
| Novavax | Incidence of Unsolicited Adverse Events (AE) | Dyspnoea | 1 Participants |
Secondary
Interferon Gamma (IFNγ) Concentrations in International Units (IU)/mL
Interferon gamma (IFNγ) concentrations as a measurement of cellular immunity will be assessed on a subset (50%) of the participants from each group. QuantiFERON Human IFN-γ SARS-CoV-2 (Qiagen) will be used to stimulate IFN-γ production in whole blood and then IFN-γ production will be measured using Enzyme-Linked ImmunoSorbent Assay (ELISA). Data will be presented as geometric mean concentration (GMC) and 95% confidence intervals (CI).
Time frame: Baseline (pre booster), Day 28, 6-months and 12-months post booster vaccination
Population: No Day 28 samples collected for Control group as no vaccine were given.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Bivalent Moderna (mRNA-1273.214) | Interferon Gamma (IFNγ) Concentrations in International Units (IU)/mL | Baseline | 0.39 IU/mL |
| Bivalent Moderna (mRNA-1273.214) | Interferon Gamma (IFNγ) Concentrations in International Units (IU)/mL | Day 28 | 1.10 IU/mL |
| Novavax | Interferon Gamma (IFNγ) Concentrations in International Units (IU)/mL | Baseline | 0.45 IU/mL |
| Novavax | Interferon Gamma (IFNγ) Concentrations in International Units (IU)/mL | Day 28 | 0.98 IU/mL |
| Control Group- no Vaccine | Interferon Gamma (IFNγ) Concentrations in International Units (IU)/mL | Baseline | 0.57 IU/mL |
Secondary
Number of IFNγ Producing Cells/Million PBMCs
IFNγ producing cells as a measurement of cellular immunity will be assessed on a subset (50%) of the participants from each group. IFN-γ Enzyme-Linked ImmunoSpot (Elispot) assay will be performed on isolated peripheral blood mononuclear cells (PBMCs) stimulated with SARS-CoV-2 specific peptides. Data will be reported as number of IFNγ producing cells/million and presented using means and 95% confidence intervals.
Time frame: Baseline (pre booster), 6, 12 and 18-months post booster vaccination
Secondary
SARS-CoV-2 Specific IgG Antibodies at Baseline (Pre Booster), and 6,12 and 18 Months Post Booster Vaccination
Serum samples collected at baseline (pre booster), 28 days, 6,12, 18, 24, and 30 months post booster vaccination from the two intervention groups and the control group will be evaluated for SARS-CoV-2 specific IgG antibodies using the commercial Euroimmun S1 IgG ELISA . Data will be reported as binding antibody units/mL and presented as geometric mean concentration and 95% confidence intervals
Time frame: Baseline (pre booster), 6-months,12-months and 18-months post booster vaccination
Population: One person in the Moderna group didn't have a blood taken at baseline
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Bivalent Moderna (mRNA-1273.214) | SARS-CoV-2 Specific IgG Antibodies at Baseline (Pre Booster), and 6,12 and 18 Months Post Booster Vaccination | 12 month anti-spike IgG GMC (95% CI) | 2047 binding antibody units (BAU/mL) |
| Bivalent Moderna (mRNA-1273.214) | SARS-CoV-2 Specific IgG Antibodies at Baseline (Pre Booster), and 6,12 and 18 Months Post Booster Vaccination | 28 day anti-spike IgG GMC (95% CI) (Note, controls did not have blood taken at 28 days) | 6792 binding antibody units (BAU/mL) |
| Bivalent Moderna (mRNA-1273.214) | SARS-CoV-2 Specific IgG Antibodies at Baseline (Pre Booster), and 6,12 and 18 Months Post Booster Vaccination | 18 month anti-spike IgG GMC (95% CI) | 4059 binding antibody units (BAU/mL) |
| Bivalent Moderna (mRNA-1273.214) | SARS-CoV-2 Specific IgG Antibodies at Baseline (Pre Booster), and 6,12 and 18 Months Post Booster Vaccination | 6 month anti-spike IgG GMC (95% CI) | 2451 binding antibody units (BAU/mL) |
| Bivalent Moderna (mRNA-1273.214) | SARS-CoV-2 Specific IgG Antibodies at Baseline (Pre Booster), and 6,12 and 18 Months Post Booster Vaccination | Baseline anti-spike IgG GMC (95% CI) | 1418 binding antibody units (BAU/mL) |
| Novavax | SARS-CoV-2 Specific IgG Antibodies at Baseline (Pre Booster), and 6,12 and 18 Months Post Booster Vaccination | Baseline anti-spike IgG GMC (95% CI) | 1434 binding antibody units (BAU/mL) |
| Novavax | SARS-CoV-2 Specific IgG Antibodies at Baseline (Pre Booster), and 6,12 and 18 Months Post Booster Vaccination | 6 month anti-spike IgG GMC (95% CI) | 1601 binding antibody units (BAU/mL) |
| Novavax | SARS-CoV-2 Specific IgG Antibodies at Baseline (Pre Booster), and 6,12 and 18 Months Post Booster Vaccination | 12 month anti-spike IgG GMC (95% CI) | 1579 binding antibody units (BAU/mL) |
| Novavax | SARS-CoV-2 Specific IgG Antibodies at Baseline (Pre Booster), and 6,12 and 18 Months Post Booster Vaccination | 18 month anti-spike IgG GMC (95% CI) | 3103 binding antibody units (BAU/mL) |
| Novavax | SARS-CoV-2 Specific IgG Antibodies at Baseline (Pre Booster), and 6,12 and 18 Months Post Booster Vaccination | 28 day anti-spike IgG GMC (95% CI) (Note, controls did not have blood taken at 28 days) | 3179 binding antibody units (BAU/mL) |
| Control Group- no Vaccine | SARS-CoV-2 Specific IgG Antibodies at Baseline (Pre Booster), and 6,12 and 18 Months Post Booster Vaccination | 18 month anti-spike IgG GMC (95% CI) | 3186 binding antibody units (BAU/mL) |
| Control Group- no Vaccine | SARS-CoV-2 Specific IgG Antibodies at Baseline (Pre Booster), and 6,12 and 18 Months Post Booster Vaccination | 6 month anti-spike IgG GMC (95% CI) | 1108 binding antibody units (BAU/mL) |
| Control Group- no Vaccine | SARS-CoV-2 Specific IgG Antibodies at Baseline (Pre Booster), and 6,12 and 18 Months Post Booster Vaccination | 12 month anti-spike IgG GMC (95% CI) | 1346 binding antibody units (BAU/mL) |
| Control Group- no Vaccine | SARS-CoV-2 Specific IgG Antibodies at Baseline (Pre Booster), and 6,12 and 18 Months Post Booster Vaccination | Baseline anti-spike IgG GMC (95% CI) | 1182 binding antibody units (BAU/mL) |
Secondary
SARS-CoV-2 Specific Neutralising Antibodies at Baseline (Pre Booster), 28 Days and 6, 12 and 18 Months Post Booster Vaccination Measured by SARS-CoV-2 Microneutralisation Assay
A subset of samples (20%) from all timepoints will be assessed using a SARS-CoV-2 microneutralisation assay to both the wild type (vaccine) strain and for two SARS-CoV-2 Variants of concern. Neutralizing antibody will be reported as endpoint titre.
Time frame: Baseline (pre booster), 6,12 and 18-months post booster vaccination
Secondary
SARS-CoV-2 Specific Neutralising Antibodies Measured by Surrogate Virus Neutralization Test (sVNT)
Neutralising antibody levels will be measured using the GenScript® cPass sVNT, which reports inhibition relative to a positive control. Results are expressed as concentrations (U/mL) and summarised as geometric mean concentrations (GMCs) with 95% CIs.
Time frame: Baseline (pre booster), 28 days, 6,12, 18, 24, and 30 months post booster vaccination
Population: No Day 28 samples collected from control group as they did not receive any vaccine.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Bivalent Moderna (mRNA-1273.214) | SARS-CoV-2 Specific Neutralising Antibodies Measured by Surrogate Virus Neutralization Test (sVNT) | Baseline Wuhan-Hu-1 SARS-CoV-2 sVNT U/mL GMC (95% CI) | 45745 U/mL |
| Bivalent Moderna (mRNA-1273.214) | SARS-CoV-2 Specific Neutralising Antibodies Measured by Surrogate Virus Neutralization Test (sVNT) | 28 days Wuhan-Hu-1 SARS-CoV-2 sVNT U/mL GMC (95% CI) | 224397 U/mL |
| Bivalent Moderna (mRNA-1273.214) | SARS-CoV-2 Specific Neutralising Antibodies Measured by Surrogate Virus Neutralization Test (sVNT) | 6 months Wuhan-Hu-1 SARS-CoV-2 sVNT U/mL GMC (95% CI) | 92355 U/mL |
| Bivalent Moderna (mRNA-1273.214) | SARS-CoV-2 Specific Neutralising Antibodies Measured by Surrogate Virus Neutralization Test (sVNT) | 12 months Wuhan-Hu-1 SARS-CoV-2 sVNT U/mL GMC (95% CI) | 46494 U/mL |
| Novavax | SARS-CoV-2 Specific Neutralising Antibodies Measured by Surrogate Virus Neutralization Test (sVNT) | Baseline Wuhan-Hu-1 SARS-CoV-2 sVNT U/mL GMC (95% CI) | 48790 U/mL |
| Novavax | SARS-CoV-2 Specific Neutralising Antibodies Measured by Surrogate Virus Neutralization Test (sVNT) | 12 months Wuhan-Hu-1 SARS-CoV-2 sVNT U/mL GMC (95% CI) | 36869 U/mL |
| Novavax | SARS-CoV-2 Specific Neutralising Antibodies Measured by Surrogate Virus Neutralization Test (sVNT) | 6 months Wuhan-Hu-1 SARS-CoV-2 sVNT U/mL GMC (95% CI) | 63682 U/mL |
| Novavax | SARS-CoV-2 Specific Neutralising Antibodies Measured by Surrogate Virus Neutralization Test (sVNT) | 28 days Wuhan-Hu-1 SARS-CoV-2 sVNT U/mL GMC (95% CI) | 96581 U/mL |
| Control Group- no Vaccine | SARS-CoV-2 Specific Neutralising Antibodies Measured by Surrogate Virus Neutralization Test (sVNT) | 6 months Wuhan-Hu-1 SARS-CoV-2 sVNT U/mL GMC (95% CI) | 48556 U/mL |
| Control Group- no Vaccine | SARS-CoV-2 Specific Neutralising Antibodies Measured by Surrogate Virus Neutralization Test (sVNT) | Baseline Wuhan-Hu-1 SARS-CoV-2 sVNT U/mL GMC (95% CI) | 63280 U/mL |
| Control Group- no Vaccine | SARS-CoV-2 Specific Neutralising Antibodies Measured by Surrogate Virus Neutralization Test (sVNT) | 12 months Wuhan-Hu-1 SARS-CoV-2 sVNT U/mL GMC (95% CI) | 33932 U/mL |
Other Pre-specified
SARS-CoV-2 Infections
SARS-CoV-2 infections were recorded throughout the 24-month follow-up period based on participant self-report of a positive RAT or PCR test. Data are reported as the number of infections occurring in each study arm during this period
Time frame: 24 months post booster vaccination
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bivalent Moderna (mRNA-1273.214) | SARS-CoV-2 Infections | 101 Reported SARS-CoV-2 infections |
| Novavax | SARS-CoV-2 Infections | 85 Reported SARS-CoV-2 infections |
| Control Group- no Vaccine | SARS-CoV-2 Infections | 78 Reported SARS-CoV-2 infections |