Nipah virus vaccine (Phylex BioSciences)

Licensed vaccines or therapeutics are rarely available for pathogens with epidemic or pandemic potential. Developing interventions for specific pathogens and defining generalizable approaches for related pathogens is a global priority and inherent to the UN Sustainable Development Goals. Nipah virus (NiV) poses a significant epidemic threat, and zoonotic transmission from bats-to-humans with high fatality rates occurs almost annually. Human-to-human transmission of NiV has been documented in recent outbreaks leading public health officials and government agencies to declare an urgent need for effective vaccines and therapeutics. Here, we evaluate NiV vaccine antigen design options including the fusion glycoprotein (F) and the major attachment glycoprotein (G). A stabilized prefusion F (pre-F), multimeric G constructs, and chimeric proteins containing both pre-F and G were developed as protein subunit candidate vaccines. The proteins were evaluated for antigenicity and structural integrity using kinetic binding assays, electron microscopy, and other biophysical properties. Immunogenicity of the vaccine antigens was evaluated in mice. The stabilized pre-F trimer and hexameric G immunogens both induced serum neutralizing activity in mice, while the post-F trimer immunogen did not elicit neutralizing activity. The pre-F trimer covalently linked to three G monomers (pre-F/G) induced potent neutralizing antibody activity, elicited responses to the greatest diversity of antigenic sites, and is the lead candidate for clinical development. The specific stabilizing mutations and immunogen designs utilized for NiV were successfully applied to other henipaviruses, supporting the concept of identifying generalizable solutions for prototype pathogens as an approach to pandemic preparedness.

Nipah virus (NiV) causes a severe neurological disease in humans. The first NiV outbreak, in Malaysia, involved pig-to-human transmission, that resulted in significant economic losses to the local pig industry. Despite the risk NiV poses to pig-dense regions, no licensed vaccines exist. This study therefore assessed three NiV vaccine candidates in pigs: (1) adjuvanted soluble NiV (s)G protein, (2) adjuvanted pre-fusion stabilised NiV (mcs)F protein, and (3) adenoviral vectored NiV G (ChAdOx1 NiV G). NiV sG induced the strongest neutralising antibody response, NiV mcsF induced antibodies best able to neutralise cell-cell fusion, whereas ChAdOx1 NiV G elicited CD8+ T-cell responses. Despite differences in immunogenicity, prime-boost immunisation with all candidates conferred a high degree of protection against NiV infection. Follow-up studies demonstrated longevity of immune responses and broadly comparable immune responses in Bangladeshi pigs under field conditions. These studies provide a platform for developing a NiV vaccine for pigs.