Abstract
Seasonal influenza viruses, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and respiratory syncytial virus (RSV) drive substantial mortality worldwide. Vaccines against these respiratory viruses are traditionally administered separately, and, while some emerging technologies have shown promise to address multiple pathogens simultaneously, subunit protein vaccines have lagged behind. Here, we describe a nanoliposome-based vaccine platform that codisplays recombinant hemagglutinin ectodomains from three seasonal influenza strains, the SARS-CoV-2 receptor binding domain, and the RSV F ectodomain, in prefusion form. In mouse, ferret, and cotton rat models, immunization elicited protective immunity against the three major respiratory viruses, with antibody responses comparable to those induced by the corresponding monovalent formulations. These findings highlight the potential for multivalent recombinant protein vaccines delivered via nanoliposome carriers to provide immunologic protection against a broad spectrum of respiratory viruses.