This clinical trial will be a blinded, randomised study to determine the safety, reactogenicity, and immunogenicity of a second booster dose of SARS-CoV-2 vaccines in adults enrolled over two consecutive stages. Stage 1 will commence at the time of study approval and transition to stage 2 once bivalent vaccines are approved and available in Australia.
Participants will be adults aged 18 years or older who have been previously primed with two doses of either Pfizer-BioNTech (BNT162b2, or Comirnaty®) or AstraZeneca (ChAdOx1-S, or Vaxzevria®) and boosted at least 3 months earlier with Pfizer BioNTech vaccine (30µg). There will be no upper age limit. Participants will be recruited from the Murdoch Children's Research Institute, the Royal Children's Hospital (RCH), the Peter Doherty Research Institute, and, if necessary, the greater Melbourne area. Ideally, 100 participants will be recruited per group unless bivalent Omicron-specific vaccines are introduced before this target is reached for monovalent ancestral vaccines. There will be 800 participants in total. Procedures will be implemented to ensure participants of all ages (aged 18 and above) are included and that there is an even age distribution in each group (\<50 and ≥50 years).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
A single standard dose (30mcg) will be administered on day 0 of the study.
A single standard dose (50mcg) of the intervention will be administered on day 0 of the study.
A single standard dose (30mcg) 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 all 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.
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-months post booster vaccination
Serum samples collected at baseline (pre booster), and 6-months post booster vaccination from all 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: Baseline (pre booster), and 6-months post booster vaccination
SARS-CoV-2 specific neutralising antibodies at baseline (pre booster), 28 days and 6-months post booster vaccination measured by surrogate virus neutralization test (sVNT)
Serum samples collected at baseline (pre booster), 28 days- and 6-months post booster vaccination from all groups will be evaluated for SARS-CoV-2 specific neutralising antibodies using the GenScript® cPass surrogate virus neutralization test (sVNT) for both wild-type and Omicron variant. Neutralising antibody response will be reported as percentage (%) inhibition of receptor binding domain-angiotensin-converting enzyme 2 (RBD-ACE2) binding relative to a positive control.
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A single standard dose (50mcg) of the intervention will be administered on day 0 of the study.
A single standard dose (BNT162b2 15μg +BNT162b2 OMI 15μg) will be administered on day 0 of the study.
A single standard dose (BNT162b2 15μg + BNT162b2 OMI 15μg)will be administered on day 0 of the study.
A single standard dose (BNT162b2 15μg + BNT162b2 OMI 15μg) will be administered on day 0 of the study.
A single standard dose (BNT162b2 15μg +BNT162b2 OMI 15μg) will be administered on day 0 of the study.
Time frame: Baseline (pre booster), 28 days and 6 months post booster vaccination
SARS-CoV-2 specific neutralising antibodies at baseline (pre booster), 28 days and 6- months post booster vaccination measured by SARS-CoV-2 microneutralisation assay
A subset of samples 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), 28 days-, and 6-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 (40%) of the participants from each group. QuantiFERON Human IFN-γ SARS-CoV-2 (Qiagen) will be used to stimulate IFN-γ production in peripheral blood mononuclear cells (PBMCs) and then IFN-γ production will be measured using ELISA. Data will be presented as geometric mean concentration (GMC) and 95% confidence intervals (CI).
Time frame: Baseline (pre booster), 28 days-, and 6-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 (40%) of the participants from each group. IFN-γ Enzyme-Linked ImmunoSpot (Elispot) assay will be performed on isolated peripheral blood mononuclear cells (PBMCs). Data will be reported as number of IFNγ producing cells/million and presented using means and 95% confidence intervals.
Time frame: Baseline (pre booster), 28 days-, and 6-months post booster vaccination
Frequency of cytokine-expressing T cells
Frequency of cytokine-expressing T cells will be assessed on a subset (40%) of participants using Flow cytometry (intracellular staining) on PBMCs samples. Data will be reported as frequency (%) of cytokine-expressing T cells presented as means and 95% CI.
Time frame: Baseline (pre booster), 28 days-, and 6-months post booster vaccination
Cytokine concentrations following PBMCs stimulation
Cytokine concentrations following PBMCs stimulation will be assessed on a subset (40%) 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), 28 days and 6-months post booster vaccination
Incidence of unsolicited adverse events (AE)
All unsolicited AE will be collected for 28 days post booster vaccination. Data will be presented as proportion of participants who report 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 proportion of participants who report unsolicited AE.
Time frame: 3 months post booster vaccination
Incidence of serious adverse events (SAE)
SAE will be collected throughout the follow-up period of 6 months post booster vaccination. Data will be presented as a proportion of participants who report unsolicited SAE.
Time frame: 6 months post booster vaccination