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
SARS-CoV-2
Vaccine

Semantics

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

Original Article

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