Immunogenicity evaluation of respiratory syncytial virus prefusogenic-F based virus-like-particles consisting of G and M proteins in mice

Abstract

Human respiratory syncytial virus (hRSV) is a major cause of severe respiratory disease in infants and young children worldwide. Studies have shown that fusion-inactive prefusogenic fusion protein (F), a partially cleaved F protein made by inserting mutations in the furin cleavage site II of the fusion protein sequence, is equally immunogenic as the prefusion F and provides higher protection than postfusion structures of the F protein. Here we have developed respiratory syncytial virus (RSV) virus-like-particles (RSV-VLPs) containing baculovirus-produced prefusogenic-F, RSV glycoprotein and matrix proteins and studied their protective efficacy in BALB/c mice. Morphology and successful assembly of VLPs were confirmed by electron microscopy and western blot. Mice immunized with the VLPs developed higher levels of serum IgG and neutralizing antibodies as compared to mice immunized with inactivated RSV. The VLPs induced higher levels of IFN-γ and IL-4, enhanced T cell responses and prevented lung pathology after RSV challenge. Overall, our results indicate that RSV-VLPs containing prefusogenic F, glycoprotein and matrix proteins are a potential vaccine candidate against RSV.