An equine herpesvirus type 1 (EHV-1) vector expressing Rift Valley fever virus (RVFV) Gn and Gc induces neutralizing antibodies in sheep

Abdelrahman Said,Mona Elmanzalawy,Guanggang Ma,Nikolaus Osterrieder,Armando Mario Damiani

doi:10.1186/s12985-017-0811-8

Abstract

Rift Valley fever virus (RVFV) is an arthropod-borne bunyavirus that can cause serious and fatal disease in humans and animals. RVFV is a negative-sense RNA virus of the Phlebovirus genus in the Bunyaviridae family. The main envelope RVFV glycoproteins, Gn and Gc, are encoded on the M segment of RVFV and known inducers of protective immunity. In an attempt to develop a safe and efficacious RVF vaccine, we constructed and tested a vectored equine herpesvirus type 1 (EHV-1) vaccine that expresses RVFV Gn and Gc. The Gn and Gc genes were custom-synthesized after codon optimization and inserted into EHV-1 strain RacH genome. The rH_Gn-Gc recombinant virus grew in cultured cells with kinetics that were comparable to those of the parental virus and stably expressed Gn and Gc. Upon immunization of sheep, the natural host, neutralizing antibodies against RVFV were elicited by rH_Gn-Gc and protective titers reached to 1:320 at day 49 post immunization but not by parental EHV-1, indicating that EHV-1 is a promising vector alternative in the development of a safe marker RVFV vaccine.

Highlights

Rift Valley fever virus (RVFV) is an arthropod-borne virus that can cause serious health problems in both animals and humans [1, 2]
We show that recombinant equine herpesvirus type 1 (EHV-1) stably expresses Glycoprotein Non-structural protein (Ns) (Gn)-Glycoprotein C (Gc) and induces a Gn-Gc-specific neutralizing antibody response in a natural host of RVFV, sheep
Our results shown that the average diameter of rH_Gn-Gc plaques was reduced in size by approximately 17% compared to parental virus (Fig. 2a); this reduction did not reach statistical significance (p = 0.31)

Summary

Introduction

Rift Valley fever virus (RVFV) is an arthropod-borne virus that can cause serious health problems in both animals and humans [1, 2]. The EHV-1 vaccine strain RacH has been cloned as an infectious bacterial artificial chromosome (BAC) [31] and developed as a universal live virus vector against various viruses. RacH has a proven safety record and can induce both humoral and cellular immune responses to transgenes introduced in the vector and provide protection in vaccinated animals, including mice, dogs, cattle and swine [32,33,34,35,36,37,38].

Results

Conclusion