Recombinant vesicular stomatitis vaccine against Nipah virus has a favorable safety profile: Model for assessment of live vaccines with neurotropic potential

Nipah virus (NiV) is a neurotropic bat-borne virus that causes inflammation of the brain. The glycoprotein of NiV binds to ephrin B2 and B3 receptors which are expressed on neural cells. A recombinant vesicular stomatitis virus-Nipah (rVSV-Nipah) vaccine was developed using reverse genetics system. The candidate live vaccine was constructed by deleting vesicular stomatitis virus (VSV) glycoprotein gene and replacing with glycoprotein genes of negative-sense single-strand RNA viruses, Ebola and Nipah virus. The Ebola glycoprotein is required for fusion and viral entry. The addition of NiV glycoprotein with ability to bind neural cells has a potential to increase neurovirulence. Therefore, safety tests for neurovirulence were conducted to assess whether the NiV glycoprotein changes tropism of the rVSV vector and if virulence factor is retained. The candidate vaccine was directly inoculated into mice and hamsters through intracerebral route. Correspondingly, rVSV-EBOV and yellow fever (YF) commercial vaccines were also inoculated as active controls. Furthermore, monkey neurovirulence test (MNVT) was conducted using monkeys. The results of MNVT showed that the candidate vaccine was significantly less neurovirulent than the live YF vaccine. The study postulated that the candidate vaccine is likely to be safer than YF which has record of safe use in humans. 

(LML)