Evaluation of A Baculovirus-Expressed VP2 Subunit Vaccine for the Protection of White-Tailed Deer (Odocoileus virginianus) from Epizootic Hemorrhagic Disease.

Sun Young Sunwoo,Kinga Urbaniak,Juergen A Richt,Velmurugan Balaraman,Mitchell V Palmer,Bonto Faburay,In Joong Kim,D Scott Mcvey,Igor Morozov,David A Meekins,Erin E Schirtzinger,Leela E Noronha,Jessie D Trujillo,William C Wilson,Barbara S Drolet

doi:10.3390/vaccines8010059

Abstract

Epizootic hemorrhagic disease virus (EHDV) is an arthropod-transmitted RNA virus and the causative agent of epizootic hemorrhagic disease (EHD) in wild and domestic ruminants. In North America, white-tailed deer (WTD) experience the highest EHD-related morbidity and mortality, although clinical disease is reported in cattle during severe epizootics. No commercially licensed EHDV vaccine is available in North America. The objective of this study was to develop and evaluate a subunit vaccine candidate to control EHD in WTD. Recombinant VP2 (rVP2) outer capsid proteins of EHDV serotypes 2 (EHDV-2) and 6 (EHDV-6) were produced in a baculovirus-expression system. Mice and cattle vaccinated with EHDV-2 or EHDV-6 rVP2 produced homologous virus-neutralizing antibodies. In an immunogenicity/efficacy study, captive-bred WTD received 2 doses of EHDV-2 rVP2 or sham vaccine, then were challenged with wild-type EHDV-2 at 30 d post vaccination. None of the rVP2-vaccinated deer developed clinical disease, no viral RNA was detected in their blood or tissues (liver, lung, spleen, kidney), and no EHDV-induced lesions were observed. Sham-vaccinated deer developed clinical disease with viremia and typical EHD vascular lesions. Here, we demonstrate a rVP2 subunit vaccine that can provide protective immunity from EHDV infection and which may serve as an effective tool in preventing clinical EHD and reducing virus transmission.

Highlights

Epizootic hemorrhagic disease (EHD) is an arthropod-transmitted viral disease of wild and domestic ruminants
To first investigate the ability of the recombinant VP2 proteins to induce neutralizing immune responses in vivo, mice were immunized with either Epizootic hemorrhagic disease virus (EHDV)-2 Recombinant VP2 (rVP2), EHDV-6 rVP2, an inactivated homologous virus, or adjuvant control (n = 5/group) at days 0 and 21
By 35 dpv, mice immunized with EHDV serotypes 2 (EHDV-2) rVP2 developed antibodies capable of neutralizing homologous virus with titers between 1:40 and 1:80

Summary

Introduction

Epizootic hemorrhagic disease (EHD) is an arthropod-transmitted viral disease of wild and domestic ruminants. The causative agent of EHD is epizootic hemorrhagic disease virus This distribution is related to the presence of its arthropod vector, namely hematophagous biting midges of the genus Culicoides [3]. The numerous strains of EHDV are categorized into seven serotypes: 1, 2, and 4-8 [4], with serotype 1, 2, and 6 viruses known to circulate in North America [5]. Serotype 2 (EHDV-2) was first isolated in North America in 1962 in Alberta, Canada, and has been the predominant serotype identified in EHD outbreaks in recent years in the United States (U.S.) [6,7,8]. Surveillance studies indicate that serotype 6 (EHDV-6), which was first detected in the U.S in 2006, likely has since become established throughout the country [9]

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