Virus-like particle vaccine by intranasal vaccination elicits protective immunity against respiratory syncytial viral infection in mice

Respiratory syncytial virus （RSV） is a leading cause of lower respiratory infection in infants and children, but there is still no licensed vaccine available. In this report, we developed virus-like par- ticle （VLP） vaccines based on the Bac-to-Bac baculovirus expression system, consisting of an influ- enza virus matrix （M1） protein and the RSV fusion protein （F） or glycoprotein （G）. These RSV VLPs were identified by western blot analysis and electron microscopy. Female BALB/c mice immunized intranasally （i.n.） with RSV-F VLPs, RSV-G VLPs, or both showed viral-specific antibody responses against RSV. Total IgG, IgG1, IgG2a, and mucosal IgA were detected in mice with RSV-F plus RSV-G VLPs, revealing potent cellular and mucosal immune responses. Moreover, we found that these mixed RSV VLPs conferred enhanced protection against live RSV challenges, showing significant decreases in lung viral replication and obvious attenuation of histopathological changes associated with viral infections. These results demonstrate that RSV-F plus RSV-G VLPs by intranasal vaccination is a prom- ising vaccine candidate that warrants further evaluation using cotton rat and primate models.