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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
496
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.
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.
Royal Children's Hospital, Murdoch Children's Research Institute
Melbourne, Victoria, Australia
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
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
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
SARS-CoV-2 Specific Neutralising Antibodies Measured by Surrogate Virus Neutralization Test (sVNT)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
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
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
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
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
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
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
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
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
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