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

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.

Perspectives on the Changing Landscape of Epizootic Hemorrhagic Disease Virus Control

“…These findings were consistent with previous studies in which cattle experimentally infected with EHDV-6 developed no, or very mild, clinical signs [77,78]. Cattle vaccinated with the recombinant VP2 proteins of EHDV-2 and EHDV-6 produced virus-neutralizing antibodies against their homologous virus serotypes; the ability to neutralize heterologous viruses was limited [73]. A recent cattle challenge study, designed to generate a panel of bovine reference sera, provided data regarding the presence and absence of cross-neutralization between serotypes [79].…”

“…A recently developed WTD fawn challenge model addressed the question of whether such maternallyderived antibodies against EHDV are protective against challenge; in this study it was demonstrated that even low titers of maternal antibodies to EHDV-2 provided protection against clinical disease and greatly reduced levels of viremia following challenge with the homologous EHDV-2 serotype virus [72]. Finally, the WTD model was recently applied to vaccine discovery, enabling the evaluation of immunogenicity and efficacy induced by a novel subunit vaccine candidate comprised of the recombinant viral capsid VP2 protein of EHDV-2 [73]. This vaccine, which was efficacious in protecting WTD from viremia and clinical disease following an experimental challenge with a virulent EHDV-2 virus, has additional benefits including potential Differentiating Infected from Vaccinated Animals (DIVA) compatibility and wider safety margins than live-attenuated vaccines.…”

“…A well-defined animal model is a quintessential research tool for advancing knowledge of pathogen transmission and pathogenesis, and an absolute requirement for countermeasure discovery and development. Despite the inherent challenges of working with WTD in research settings, experimental infections in deer have provided insights into host susceptibility, pathogenesis, and immune responses since the initial determination that EHD was a viral disease [10,[64][65][66][67][68][69][70][71][72][73]). Recent advances using in vivo WTD studies include the determination that deer were susceptible to experimental challenge with the emerging serotype EHDV-6, and that the EHDV-6-infected animals presented with clinical signs, pathological abnormalities, and postmortem findings consistent with studies of other EHDV serotypes in WTD [71].…”

Infection and transmission of ancestral SARS-CoV-2 and its alpha variant in pregnant white-tailed deer

“…Five of the six deer were pregnant; the number of fetuses per deer are indicated in Table 1. Four naïve white-tailed deer from a previous study evaluating a baculovirus-expressed subunit vaccine for the protection from epizootic hemorrhagic disease (EHD), performed in 2017 9 , were used as controls (Table 1 and Figure 1).…”

A Duplex Fluorescent Microsphere Immunoassay for Detection of Bluetongue and Epizootic Hemorrhagic Disease Virus Antibodies in Cattle Sera

“…With its considerable animal health and economic impact, bluetongue disease is a World Organization for Animal Health (OIE)-reportable disease [ 19 , 22 ]. Control methods for BTV include limited vaccines [ 23 , 24 , 25 , 26 ], livestock management [ 27 , 28 ], and vector control [ 29 ], with EHDV control often emulating standards set by BTV research [ 30 , 31 , 32 ].…”