Universal protection against SARS-CoV-2 viruses by multivalent mRNA vaccine in mice

The continual emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants challenges available SARS-CoV-2 vaccines for adequate control of outbreaks. Currently, universal vaccines capable of obviating the need for exact strain matching between mRNA vaccines and circulating viruses are absent. In this study, we designed, manufactured, and evaluated a nucleoside-modified lipid nanoparticle mRNA vaccine, aimed for offering broad-spectrum protection against recent SARS-CoV-2 variants. Additionally, the protection efficiency of monovalent, bivalent, quadrivalent, and XBB.1.5 mRNA vaccines was compared with the proposed universal vaccine. The neutralizing antibody activity against wuhan-1, BA.4/5, XBB.1.5, B.1.1.529, BQ.1.1, EG.5.1 and JN.1 was assessed using enzyme-linked immunosorbent assay, rapid fiber-optic biolayer interferometry-based biosensor, and pseudovirus neutralization test. Our results reveal that the proposed multivalent vaccine affords comprehensive protection against previously circulating, current and previously unidentified SARS-CoV-2 strains.