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Interim Results from a Phase I Trial of Novel SARS-CoV-2 Beta Variant Receptor-Binding Domain Recombinant Protein and mRNA Vaccines as a 4 th Dose Booster
43 Pages Posted: 29 Jun 2023
More...Abstract
Background: SARS-CoV-2 booster vaccination should ideally enhance protection against variants and minimise immune imprinting. This Phase I trial evaluated two vaccines targeting SARS-CoV-2 beta-variant receptor-binding domain (RBD): a recombinant dimeric RBD-human IgG1 Fc-fusion protein, and an mRNA encoding a membrane-anchored RBD.
Methods: 76 healthy adults aged 18–64y, previously triple vaccinated with licensed SARS-CoV-2 vaccines, were randomised to receive a 4th dose of either an adjuvanted (MF59®, CSL Seqirus) protein vaccine (5, 15 or 45µg, N=32), mRNA vaccine (10, 20, or 50µg, N=32), or placebo (saline, N=12) at least 90 days after a 3rd boost vaccination or SARS-CoV-2 infection. Bleeds occurred on days 1 (prior to vaccination), 8, and 29. ClinicalTrials.gov NCT05272605.
Findings: No vaccine-related serious or medically attended adverse events occurred. The protein vaccine reactogenicity was mild, whereas the mRNA vaccine was moderately reactogenic at higher dose levels. Best anti-RBD antibody responses resulted from the higher doses of each vaccine. A similar pattern was seen with live virus neutralisation and surrogate, and pseudovirus neutralisation assays. Breadth of immune response was demonstrated against BA.5 and more recent omicron subvariants (XBB, XBB.1.5 and BQ.1.1). Binding antibody titres for both vaccines were comparable to those of a licensed bivalent mRNA vaccine. Both vaccines enhanced CD4+ and CD8+ T cell activation.
Interpretation: There were no safety concerns and the reactogenicity profile was mild and similar to licensed SARS-CoV-2 vaccines. Both vaccines showed strong immune boosting against beta, ancestral and omicron strains.
Trial Registration: The study is registered at www.clinicaltrials.gov (NCT05272605).
Funding: Medical Research Future Fund, and philanthropies Jack Ma Foundation and IFM investors.
Declaration of Interest: The vaccines evaluated in this Phase I study were the result of independent University of Melbourne and Monash University research and development, with funding provided by the Australian Government’s Medical Research Future Fund (MRFF), the National Health and Medical Research Council (NHMRC) and philanthropic funders. The MF59 for the protein-RBD candidate was donated by CSL Seqirus. One author (SR) is an employee of CSL Seqirus and he also has an adjunct (honorary) appointment to the University of Melbourne. Several authors have received research or consulting funding from various commercial entities, but none is judged to be in conflict with the work presented.
Ethical Approval: The study was reviewed and approved by the Royal Melbourne Hospital Human Research Ethics Committee and was conducted under the Clinical Trial Notification (CTN) Scheme (CTN ID: 04968-1) administered by the Australian Therapeutic Goods Administration. All participants provided written informed consent prior to enrolment.
Keywords: SARS-CoV-2, vaccine, receptor binding domain, recombinant protein, mRNA, beta variant, phase I trial.
Suggested Citation: Suggested Citation