Interim results from a phase I randomized, placebo-controlled trial of novel SARS-CoV-2 beta variant receptor-binding domain recombinant protein and mRNA vaccines as a 4th dose booster.

Publication date: Nov 27, 2023

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 IgG F-fusion protein, and an mRNA encoding a membrane-anchored RBD. 76 healthy adults aged 18-64 y, previously triple vaccinated with licensed SARS-CoV-2 vaccines, were randomised to receive a 4th dose of either an adjuvanted (MF59(R), CSL Seqirus) protein vaccine (5, 15 or 45 μg, N = 32), mRNA vaccine (10, 20, or 50 μg, 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. govNCT05272605. 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. 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. Australian Government Medical Research Future Fund, and philanthropies Jack Ma Foundation and IFM investors.

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Concepts Keywords
4th Beta variant
Australian mRNA
Govnct05272605 Phase I trial
Live Receptor binding domain
Vaccine Recombinant protein


Type Source Name
disease VO dose
disease VO vaccination
drug DRUGBANK Immune Globulin Human
disease VO vaccinated
disease VO vaccine
disease VO boost vaccination
disease MESH SARS-CoV-2 infection
pathway REACTOME SARS-CoV-2 Infection
disease IDO immune response

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