Development of a J paramyxovirus-based vaccine vector

J paramyxovirus (JPV) is a non-segmented, negative-strand RNA virus in the Jeilongvirus genus of the Paramyxoviridae family. Recently, a recombinant JPV lacking the small hydrophobic protein (SH) gene (rJPV-∆SH) has been used as a viral vector for avian influenza virus H5N1 and HIV vaccine development. However, the rJPV-∆SH vector still causes morbidity and mortality in mice. To further develop this vaccine platform, we generated multiple recombinant JPV (rJPV) mutants and tested their pathogenicity in mice. We found that rJPV lacking the syncytial protein (SP) (rJPV-∆SP), rJPV with both SH and SP genes deleted (rJPV-ΔSHΔSP) and a JPV lacking coding sequences for SH, SP, and the putative X open reading frame (rJPV-∆3) were pathogenic in mice. Incorporating mutations in the L gene that mediate pathogenesis into rJPV-∆3 (rJPV-∆3-LW-L) resulted in a fully attenuated virus in mice. rJPV∆3-LW-L-immunized mice were protected during lethal JPV challenge. Furthermore, intranasally administrated rJPV-∆3-LW-L expressing Nipah virus (NiV) fusion (F) induced anti-NiV-F antibodies in mice and Syrian hamsters, and a single-dose intranasal immunization with rJPV-∆3-NiV-F-LW-L induced complete protection against lethal NiV challenge in the hamster model. Our work has identified a novel intranasal vaccine vector that is fully attenuated in mice and induces protective immunity in animals.