Jason P. Laliberte, Yíngyún Caì, Tara Kenny, Yi Zhang, Kuishu Ren, Kim Rosenthal, Daniel Flores, Richard Roque, Oliver J. Acton, Vanessa Cadevilla Peano, Noel Janney, Vinita Puri, Sarah Siddiqui, Angela D. Pack, Giune Padilla, Seme Diallo, Hibret A. Adissu, Rakesh Choudhary, Hawley C. Pruitt, Yihan Cheng, George Thom, Michael R. Newton, Cheyne Kurokawa, Johnathan D. Guest, Phillip A. Swanson, Yueh–Ming Loo, Joseph R. Francica, Wade Blair, Mark T. Esser
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.