Rabies-based vaccine induces potent immune responses against Nipah virus

Abstract

Nipah Virus (NiV) is a re-emerging zoonotic pathogen in the genus Henipavirus of the Paramyxoviridae family of viruses. NiV is endemic to Bangladesh and Malaysia and is highly fatal to both livestock and humans (human case fatality rate = 74.5%). Currently, there is no approved vaccine against NiV on the market. The goal of this study was to use a recombinant RABV vector expressing NiV glycoprotein (NiV G) to develop a bivalent candidate vaccine against NiV disease and rabies virus (RABV) disease, which is also a significant health burden in the regions where NiV is endemic. The rabies vector is a well-established vaccine strain that lacks neurovirulence and can stably expresses foreign antigens that are immunogenic in various animal models. Mice inoculated intranasally with the live recombinant RABV/NiV vaccine (NIPARAB) showed no signs of disease. To test the immunogenicity of the vaccine candidate, groups of C57BL/6 mice were immunized intramuscularly with a single dose of live vaccine particles or two doses of chemically inactivated viral particles. Both vaccination groups showed NiV G-specific seroconversion, and the inactivated (INAC) vaccine group yielded higher titers of NiV G-specific antibodies. Furthermore, cross-reactivity of NiV G-specific immune sera against Hendra virus (HeV), was confirmed by immunofluorescence (IF) and indirect ELISA against soluble recombinant HeV glycoprotein (HeV G). Both live and killed vaccines induced neutralizing antibodies. These results indicate that NIPARAB may be used as a killed virus vaccine to protect humans against NiV and RABV, and possibly as a preventative measure against HeV as well.

Strategic Development of a Next-Generation Multi-Epitope Vaccine To Prevent Nipah Virus Zoonotic Infection

“…31 The bivalent rabies virus vaccine is in pipeline against the NiV and rabies virus, as it has shown good immune response in animal model. 32 The described vaccines were mainly tested on animals and not licensed for the NiV treatment in humans. All reported vaccines primarily composed of single viral protein, and it is a well-known phenomenon that, RNA viruses have a high mutation rate, to prompt alteration of viral genome and proteome.…”

Development and Applications of Viral Vectored Vaccines to Combat Zoonotic and Emerging Public Health Threats

“…That being said, some RABV-based vectors have been shown to stably express up to 4.4 kB of insert, which is more than 50% of their genome size [ 168 ]. RABV vectors have been used for vaccine development against different pathogens, including HIV-1 and Nipah virus [ 169 , 170 , 171 , 172 ]. In the Nipah vaccine study, an RC RABV-based vaccine expressing the Nipah virus (NiV) glycoprotein (G) was created for evaluation in mice.…”

“…In the Nipah vaccine study, an RC RABV-based vaccine expressing the Nipah virus (NiV) glycoprotein (G) was created for evaluation in mice. The vaccine induced a strong neutralizing antibody response that was also cross-reactive against a related Hendra virus [ 172 ]. Specifically, the antibodies were mainly IgG2c, which suggested a Th1-biased response [ 172 ].…”

Recent advances in the understanding of Nipah virus immunopathogenesis and anti-viral approaches

“…Several vaccine development strategies have recently been studied in small-animal models, including chimeric rabies-based 88 , virus-like particle (VLP)-based 89 , adenovirus-based 90 , and epitope-based 91, 92 vaccines. Those approaches induced a protection against NiV by triggering a specific response against its envelope glycoprotein G that will require further development using non-human primates to evaluate their efficiency and safety.…”