Bovine Herpesvirus-4-Vectored Delivery of Nipah Virus Glycoproteins Enhances T Cell Immunogenicity in Pigs.

Miriam Pedrera,Gaetano Donofrio,Ariel Isaacs,Jean-Christophe Audonnet,Luca Russo,Glenn A Marsh,Keith Chappell,Francesca Macchi,Shawn Todd,Daniel Watterson,Paul R Young,Simon P Graham,Dalan Bailey,Valentina Franceschi,Nazia Thakur,Elma Z Tchilian,Lobna Medfai,Rebecca K Mclean

doi:10.3390/vaccines8010115

Abstract

Nipah virus (NiV) is an emergent pathogen capable of causing acute respiratory illness and fatal encephalitis in pigs and humans. A high fatality rate and broad host tropism makes NiV a serious public and animal health concern. There is therefore an urgent need for a NiV vaccines to protect animals and humans. In this study we investigated the immunogenicity of bovine herpesvirus (BoHV-4) vectors expressing either NiV attachment (G) or fusion (F) glycoproteins, BoHV-4-A-CMV-NiV-GΔTK or BoHV-4-A-CMV-NiV-FΔTK, respectively in pigs. The vaccines were benchmarked against a canarypox (ALVAC) vector expressing NiV G, previously demonstrated to induce protective immunity in pigs. Both BoHV-4 vectors induced robust antigen-specific antibody responses. BoHV-4-A-CMV-NiV-GΔTK stimulated NiV-neutralizing antibody titers comparable to ALVAC NiV G and greater than those induced by BoHV-4-A-CMV-NiV-FΔTK. In contrast, only BoHV-4-A-CMV-NiV-FΔTK immunized pigs had antibodies capable of significantly neutralizing NiV G and F-mediated cell fusion. All three vectored vaccines evoked antigen-specific CD4 and CD8 T cell responses, which were particularly strong in BoHV-4-A-CMV-NiV-GΔTK immunized pigs and to a lesser extent BoHV-4-A-CMV-NiV-FΔTK. These findings emphasize the potential of BoHV-4 vectors for inducing antibody and cell-mediated immunity in pigs and provide a solid basis for the further evaluation of these vectored NiV vaccine candidates.

Highlights

Nipah virus (NiV), along with the related Hendra virus (HeV), are classified as members of the Henipavirus genus within the Paramyxoviridae family [1]
After 48 h post-infection, the cytopathic effect (CPE) was evident in cell monolayers, indicating their capability to support BoHV-4 replication and these observations were confirmed by an increase in viral titers in the supernatants between 24, 48 and 72 h post-infection (Supplementary Figure S1B)
Whilst an increasing proportion of Asian pork is produced in intensive systems, in developing areas, most of the population is still engaged in small-scale farming, with households keeping ‘backyard’ livestock including pigs

Summary

Introduction

Nipah virus (NiV), along with the related Hendra virus (HeV), are classified as members of the Henipavirus genus within the Paramyxoviridae family [1]. The viral genome is encapsidated by the nucleoprotein (N) and complexes with the viral phosphoprotein (P) and polymerase (L) to form the ribonucleoprotein (RNP). The RNP is surrounded by the viral envelope, which consists. Vaccines 2020, 8, 115 of the surface glycoproteins for attachment (G) and fusion (F), and the inner matrix protein (M), which is required for viral assembly and budding [2]. The G protein is responsible for binding to host cell surface receptors; for NiV this has been shown to be ephrin-B2 and ephrin-B3 [3]. NiV F is synthesized as an inactive precursor F0, which is proteolytically cleaved by a host cell protease, into the fusion active F1 and F2 subunits, which facilitate cell-to-cell spread of virus [4]. Two genetically distinct strains have been described, Malaysia (NiV-M) with a genome length of 18,246 bp and Bangladesh (NiV-B)

Methods

Results

Conclusion