Development of low bio-containment assays to characterise the antibody responses in pigs to Nipah virus vaccine candidates

Abstract

Nipah virus (NiV) is a zoonotic paramyxovirus that causes severe and often fatal respiratory and neurological disease in humans. Since 1998, NiV outbreaks have occurred in Malaysia, Bangladesh and India. NiV poses a significant pandemic threat due to its broad host range and the widespread distribution of its natural host, the Pteropus fruit bat. Despite this, there are currently no licenced therapeutics or vaccines for use in either humans or livestock. Aiming to develop a safe and inexpensive vaccine to protect livestock in future outbreaks and to prevent onward transmission to humans, we are evaluating the immunogenicity and efficacy of three candidate vaccines in pigs. These vaccines are based on the NiV G or F surface glycoproteins, proteins which are essential for mediating virus-cell or cell-cell entry. The candidate vaccines include: (i) a recombinant soluble NiV G protein subunit, (ii) a recombinant molecular clamp stabilised NiV F protein subunit and (iii) a replication deficient, adenoviral vectored NiV G protein. We have developed low biocontainment assays to characterise the antibody responses to NiV and to aid identification of immune correlates of protection through quantification of both antigen-specific and neutralising antibody responses to our vaccine candidates. This includes anti-NiV F/G indirect ELISAs, a microneutralisation test using pseudotyped particles, and a microfusion inhibition test using a quantifiable cell-cell fusion assay. Using these assays we have demonstrated that all three of our novel vaccines are immunogenic in pigs and capable of generating a robust antibody response, with evidence for neutralising antibodies.