Vaccine candidate based on a baculovirus expressed VP2 provides full protection from epizootic hemorrhagic disease virus serotype 8 in calves

Epizootic hemorrhagic disease virus serotype 8 (EHDV-8) has recently emerged in Europe, causing widespread outbreaks in cattle and wild ruminant populations. The lack of commercial vaccines at the time of emergence highlighted the urgent need to develop effective vaccines for disease control. Therefore, we developed and evaluated the safety and efficacy of a novel subunit candidate vaccine against EHDV-8, based on the recombinant VP2 protein (rVP2) from EHDV-8 expressed in a baculovirus system. Ten Holstein-Friesian calves were randomly assigned to vaccinated (n = 5) or control (n = 5) groups. Animals in the vaccinated group received two doses of 200 μg of rVP2 protein 21 days apart, while control animals were sham-vaccinated. Fourteen days after the booster dose, both groups were challenged with a field strain of EHDV-8. Clinical signs were recorded daily, and blood samples were collected at regular intervals to assess viremia and immune response. The rVP2 vaccine candidate was well tolerated, with only transient, low-grade fever and mild local reactions. Vaccinated calves developed neutralizing antibodies by day 28 post-vaccination and, upon EHDV-8 challenge on day 35 post-vaccination, showed no clinical signs or viremia. In contrast, all control calves developed viremia, mild clinical signs, and EHDV-specific antibodies after challenge. Notably, vaccinated animals remained negative by VP7 ELISA even post-challenge, indicating that the rVP2-based vaccine afforded protection from viral replication and disease and enabled DIVA (Differentiating Infected from Vaccinated Animals) capability. In conclusion, these results demonstrate that the rVP2-based subunit vaccine confers complete protection from EHDV-8 under experimental conditions in cattle, indicating the possibility of its use for disease control strategies.