A live attenuated pseudorabies virus vectored Nipah vaccine for enhanced protection in pigs

Pig-to-human transmission was responsible for the first and most severe Nipah virus (NiV) outbreak in Malaysia and Singapore in 1998-99\. This outbreak was controlled by culling almost half of all pigs in Malaysia, which caused severe and lasting economic damage to the local pig industry. Despite the threat NiV poses to some of the most pig dense regions of the world, no vaccines are currently available. Commercial development of NiV vaccines is limited, since animal health companies are of the opinion that there will be limited marketability due to the sporadic nature of spillover outbreaks. To address this gap, we are developing a vaccine for use in pigs that would reduce the risk that NiV poses to the pig industry, livestock keepers and public health. We have demonstrated that immunisation of pigs with either the NiV G or F glycoproteins, using a two-shot immunisation regime, provides a high level of protection against NiV. However, the protection is lost when pigs are challenged after a single immunisation. A NiV vaccine for pigs could be deployed in response to an emergency outbreak situation or routinely used to reduce the risk of NiV outbreaks occurring. The proposed project aims to address the requirements for both scenarios by evaluating a vaccine candidate that may provide rapid immunity after a single immunisation and could also be used as a bivalent vaccine. Live attenuated pseudorabies virus (PrV) vaccines are highly effective vaccines that have enabled the eradication of PrV from large parts of Europe and America. Live attenuated PrV can be readily engineered to express antigens from other pathogens and serve as potent vaccine vectors. This project will evaluate whether live attenuated PrV expressing both NiV G and F can elicit protective immune responses after a single immunisation. If successful, this vaccine could also be exploited as a bivalent vaccine. Since pigs in the NiV endemic region are routinely vaccinated with live attenuated PrV vaccines, this could present an economically viable approach to mass immunisation, which would significantly reduce the risk of NiV outbreaks emerging through pigs. Approvals for both preventative and reactive use NiV vaccines will be reliant on the availability of diagnostic tests that are able to discriminate infected from vaccinated animals. We will therefore evaluate the potential of recombinant NiV nucleocapsid, phosphoprotein, and matrix proteins to detect antibodies in infected but not vaccinated pigs.