A bivalent vaccine to reduce the risk of Nipah virus outbreaks

Pig-to-human transmission was responsible for the most severe Nipah virus (NiV) outbreak, which was controlled by culling almost half the Malaysian pig population. Despite the threat NiV poses, no vaccines are available. Commercial development of NiV vaccines is limited since companies fear limited marketability due to the sporadic nature of outbreaks. To address this gap, we are developing a dual purpose (bivalent) vaccine for pigs.

We previously demonstrated that immunisation of pigs with NiV G or F glycoproteins, using a two-shot immunisation regime, provides a high level of protection against NiV. A NiV vaccine for pigs could be deployed in response to an outbreak situation, or routinely used to reduce the risk of NiV outbreaks occurring. We aim to address both scenarios by developing a vaccine that can provide immunity after a single immunisation and/or can be used as a bivalent vaccine. Live attenuated pseudorabies virus (PrV) vaccines are highly effective vaccines that can be engineered to express antigens from other pathogens. We constructed a PrV vaccine that produced both the NiV F and G glycoproteins. The NiV-neutralising antibody response stimulated by prime-boost vaccination was comparable to those seen with protective vaccine candidates. The inclusion of the NiV proteins into the PrV vaccine did not hinder PrV-specific immune responses. Overall, the data suggested that the bivalent PrV-NiV vaccine candidate would likely provide protection against both viruses. However, the immune responses suggest that two doses may be required.

We now aim to improve the vaccine so that it may provide protection after a single immunisation. We shall do this by engineering the NiV glycoproteins so that they are expressed on the surface of cells, which should enhance antibody responses. We will compare the new and original vaccine to determine whether we have improved immunogenicity. The best candidate will then be tested for its ability to protect pigs against both PrV and NiV infections. Current PrV vaccines need to be kept refrigerated, which can be challenging in the tropical region at risk from NiV. Therefore, we will evaluate stabilising the vaccine by fine coating it with silica. Since NiV infection restricts the ability of countries to trade pigs or pig products, it is essential that any NiV vaccine has a companion test that enable the discrimination of infected from vaccinated pigs. We have established a lab-based assay that allows such discrimination and will translate this to a rapid 'penside' test.