Immunogenicity and efficacy of an mRNA vaccine expressing a virus-like particle spike antigen against SARS-CoV-2

The COVID-19 pandemic spurred mRNA vaccine innovation, but new SARS-CoV-2 variants highlight the need for vaccines with improved potency and durability. This report presents a novel mRNA vaccine platform encoding virus-like particle antigens (mRNA-VLPs) that mimic native virus structures, aiming to boost antibody responses via enhanced B cell activation. In animal studies, mRNA-VLP vaccines generated stronger neutralizing antibody responses across multiple variants compared to conventional mRNA vaccines expressing native spike proteins. In non-human primates, these elevated antibodies lasted at least six months. An mRNA-VLP vaccine encoding the Omicron spike outperformed traditional mRNA vaccines in mice as both a monovalent and bivalent (with ancestral spike) formulation. In hamsters, even low doses of mRNA-VLP vaccine provided complete protection, similar to high doses of native spike mRNA vaccines. These results suggest the mRNA-VLP platform could significantly strengthen vaccine efficacy and breadth against evolving SARS-CoV-2 variants.