Javier Ortego, CISA-INIA, CSIC

Luis Jiménez-Cabello, Sergio Utrilla-Trigo, Alejandro Carra-Valenzuela, Iván Mazuecos, Iván Belinchón, Eva Calvo-Pinilla, Javier Ortego. CISA-INIA, CSIC

Vaccines

Epizootic hemorrhagic disease (EHD), caused by Epizootic hemorrhagic disease virus (EHDV), is an emerging and severe livestock disease. Recent incursion and distribution of EHDV in Europe have outlined the emerging character of EHD. A range of inconveniences restricts utilization of natural hosts of EHDV for research purpose. Previously, we showed that adult mice deficient in type I IFN receptor (IFNAR(-/-)) were highly susceptible to EHDV-6 and EHDV-8 infection. Importantly, IFNAR(-/-)mice immunized with a EHDV-8 inactivated vaccine elicited neutralizing antibodies specific of EHDV-8 and afforded full protection against challenge with a lethal dose of this virus, confirming its application for preliminary vaccine testing. Here, we have designed modified vaccinia virus Ankara (MVA)-vectored vaccines that express protein VP2 of EHDV-8 or protein VP7 of EHDV-2. Prime-boost immunization of IFNAR(-/-) mice with the MVA-VP2 vaccine candidate induced high titers of EHDV-8-specific neutralizing antibodies (NAbs) and conferred full protection against the homologous lethal challenge. However, no heterologous protection was observed after lethal challenge with EHDV-6. In contrast, the MVA-VP7 vaccine candidate elicited strong cytotoxic CD8+ T-cell responses against VP7 and conferred complete protection against lethal challenge with either EHDV-8 or 6 in IFNAR(-/-) mice in the absence of NAbs, being the first multiserotype vaccine candidate described against EHDV so far. Hence, we present novel DIVA vaccine candidates against EHDV and we identified the conserved protein VP7 as an antigen capable of inducing multiserotype protection, one of the major challenges in vaccine research against orbiviruses.