Immunization With Bovine Herpesvirus-4-Based Vector Delivering PPRV-H Protein Protects Sheep From PPRV Challenge.

Daniel Rodríguez-Martín,Valentina Franceschi,Noemí Sevilla,Verónica Martín,Luca Russo,Gaetano Donofrío,Francesca Macchi,José Manuel Rojas

doi:10.3389/fimmu.2021.705539

Abstract

The Morbillivirus peste des petits ruminants virus (PPRV) is the causal agent of a highly contagious disease that mostly affects sheep and goats and produces considerable losses in developing countries. Current PPRV control strategies rely on live-attenuated vaccines, which are not ideal, as they cannot differentiate infected from vaccinated animals (DIVA). Recombinant vector-based vaccines expressing viral subunits can provide an alternative to conventional vaccines, as they can be easily paired with DIVA diagnostic tools. In the present work, we used the bovine herpesvirus-4-based vector (BoHV-4-A) to deliver PPRV hemagglutinin H antigen (BoHV-4-A-PPRV-H-ΔTK). Vaccination with BoHV-4-A-PPRV-H-ΔTK protected sheep from virulent PPRV challenge and prevented virus shedding. Protection correlated with anti-PPRV IgGs, neutralizing antibodies and IFN-γ-producing cells induced by the vaccine. Detection of antibodies exclusively against H-PPRV in animal sera and not against other PPRV viral proteins such as F or N could serve as a DIVA diagnostic test when using BoHV-4-A-PPRV-H-ΔTK as vaccine. Our data indicate that BoHV-4-A-PPRV-H-ΔTK could be a promising new approach for PPRV eradication programs.

Highlights

Peste des petits ruminants virus (PPRV) is a Morbillivirus that primarily affects domestic and wild ruminants
Ovine fetal lung (OFL) proved to be totally permissive to recombinant bovine herpesvirus-4 (BoHV-4)-EGFP-DTK infection (Figure 1A) reaching a good titer (Figure 1B) and to efficiently express peste des petits ruminants virus (PPRV)-H antigen when infected with the BoHV-4-A-PPRV-H-DTK recombinant vector, as shown by Western blot analysis (Figure 1C)
In this protocol, OFLs were expanded in a medium with 10% of fetal bovine serum (FBS) until they reached 90% of confluence, infected with BoHV-4A-PPRV-H-DTK and BoHV-4-A-DTK at low moi (0.5) in media containing 2% sheep serum

Summary

Introduction

Peste des petits ruminants virus (PPRV) is a Morbillivirus that primarily affects domestic and wild ruminants. Single immunization with live PPRV vaccines has been able to maintain protective levels of serum antibody for up to 3 years, with antibody patterns undistinguishable from the ones generated after a natural infection. These live vaccines are, thermosensitive and require an efficacious cold chain to remain active, which can be problematic in PPRV-endemic countries usually situated in warm climate areas. DIVA vaccines are suited for disease control in disease-free regions that are at risk of outbreaks It is ideal for eradication programs in endemic regions as it permits surveillance after finishing vaccination campaigns, so that animal trade can be resumed. PPRV has been proposed as the disease for global eradication by the OIE and the Food and Agriculture Organization of the United Nations (FAO), and developing a DIVA vaccine for PPRV is highly attractive to help in this objective

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Conclusion