Bovine Herpesvirus-4-Based Vector Delivering Peste des Petits Ruminants Virus Hemagglutinin ORF Induces both Neutralizing Antibodies and Cytotoxic T Cell Responses.

Francesca Macchi,José Manuel Rojas,Verónica Martín,Gaetano Donofrio,Noemí Sevilla,Sandro Cavirani,Valentina Franceschi,Giulia Tebaldi,Andrea Elizabeth Verna

doi:10.3389/fimmu.2018.00421

Abstract

Peste des Petits Ruminants Virus (PPRV) is an extremely infective morbillivirus that primarily affects goats and sheep. In underdeveloped countries where livestock are the main economical resource, PPRV causes considerable economic losses. Protective live attenuated vaccines are currently available but they induce antibody responses similar to those produced in PPRV naturally infected animals. Effective vaccines able to distinguish between vaccinated and naturally infected animals are required to PPRV control and eradication programs. Hemagglutinin (H) is a highly immunogenic PPRV envelope glycoprotein displaying both hemagglutinin and neuraminidase activities, playing a crucial role in virus attachment and penetration. In this study, a recombinant Bovine Herpesvirus-4 (BoHV-4)-based vector delivering an optimized PPRV-Hemagglutinin expression cassette, BoHV-4-A-PPRV-H-ΔTK, was assessed in immunocompetent C57BL/6 mice. BoHV-4-A-PPRV-H-ΔTK-immunization elicited both cellular and humoral immune responses with specific T cell, cytotoxic T lymphocyte, and sero-neutralizing antibody against PPRV. These data suggest recombinant BoHV-4-A-PPRV-H-ΔTK as an effective vaccine candidate to protect against PPRV herd infection and potentially applicable for eradication programs.

Highlights

Peste des Petits Ruminants (PPR) is an often fatal, highly contagious, and devastating disease affecting domestic small ruminants and especially goats
The so obtained pBAC-Bovine herpesvirus 4 (BoHV-4)-A-Peste des Petits Ruminants Virus (PPRV)-HΔTK recombinant viral genome authenticity was first assessed by HindIII restriction enzyme analysis and confirmed by Southern Blotting using a peste des petits ruminants virus hemagglutinin (PPRV-H) specific probe
BoHV4-A-PPRV-H-ΔTK showed no replication defects comparing with the BoHV-4-A parental strain (Figure 1D) and expressed PPRV-H protein (Figure 1E)

Summary

Introduction

Peste des Petits Ruminants (PPR) is an often fatal, highly contagious, and devastating disease affecting domestic small ruminants and especially goats. H glycoprotein is an immunodominant antigen which, alone, can stimulate a protective immune-response when delivered by several viral vectors, mainly based on adenovirus [2,3,4] and poxvirus [5, 6]. These antigen immune-properties would allow the generation of a Differentiating Infected from Vaccinated Animals (DIVA) vaccine. BoHV4-A-PPRV-H-ΔTK immunized mice developed both PPRV neutralizing antibodies and PPRV specific T-cell responses These data indicate that this BoHV-4-based vector could be an effective PPR vaccine candidate for small ruminants that could distinguish between infected and vaccinated animals

Methods

Results

Conclusion