Jiménez-Cabello Luis, Utrilla-Trigo Sergio, Rodríguez-Sabando Karen, Carra-Valenzuela Alejandro, Illescas-Amo Miguel, Calvo-Pinilla Eva, Ortego Javier
Centro de Investigación en Sanidad Animal (CISA), Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Valdeolmos, Madrid, Spain.
J Virol. 2024 Dec 17;98(12):e0168724. doi: 10.1128/jvi.01687-24. Epub 2024 Nov 7.
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 need for vaccine research against this viral disease. In this work, we report modified vaccinia virus Ankara (MVA)-vectored vaccines designed to express protein VP2 of EHDV-8 or protein VP7 of EHDV-2. Prime boost immunization of adult IFNAR(-/-) mice with the MVA-VP2 vaccine candidate induced high titers of EHDV-8-specific neutralizing antibodies (NAbs) and conferred full protection against homologous lethal challenge with EHDV-8. 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 EHDV-6 in IFNAR(-/-) mice in the absence of NAbs, being the first multiserotype vaccine candidate against EHDV. Moreover, we expressed recombinant proteins VP2 and VP7 of EHDV in the baculovirus expression system, which were used to analyze the potential DIVA (differentiating infected from vaccinated animals) character of these vaccine candidates.IMPORTANCEEmergence and re-emergence of arthropod-borne viruses are major concerns for both human and animal health. The most recent example is the fast expansion of EHDV-8 through Europe. Besides, EHDV-8 relates with a high prevalence of pathologic cases in cattle populations. No vaccine is currently available in Europe, and vaccine research against this arboviral disease is negligible. In this work, we present novel DIVA vaccine candidates against EHDV, and most importantly, we identified the protein VP7 of EHDV as an antigen capable of inducing multiserotype protection, one of the major challenges in vaccine research against orbiviruses.
由流行性出血病病毒（EHDV）引起的流行性出血病（EHD）是一种新出现的严重家畜疾病。EHDV最近在欧洲的侵入和传播凸显了针对这种病毒性疾病进行疫苗研究的必要性。在这项研究中，我们报告了经改造的安卡拉痘苗病毒（MVA）载体疫苗，其设计用于表达EHDV - 8的VP2蛋白或EHDV - 2的VP7蛋白。用MVA - VP2候选疫苗对成年IFNAR（-/-）小鼠进行初免-加强免疫，可诱导产生高滴度的EHDV - 8特异性中和抗体（NAbs），并对EHDV - 8的同源致死性攻击提供完全保护。然而，在用EHDV - 6进行致死性攻击后未观察到异源保护。相比之下，MVA - VP7候选疫苗引发了针对VP7的强烈细胞毒性CD8 + T细胞反应，并在没有NAbs的情况下，对IFNAR（-/-）小鼠的EHDV - 8或EHDV - 6致死性攻击提供了完全保护，是首个针对EHDV的多血清型候选疫苗。此外，我们在杆状病毒表达系统中表达了EHDV的重组蛋白VP2和VP7，用于分析这些候选疫苗的潜在鉴别诊断（DIVA，区分感染动物和接种动物）特性。
节肢动物传播病毒的出现和再次出现对人类和动物健康都是主要关注点。最近的例子是EHDV - 8在欧洲的快速传播。此外，EHDV - 8与牛群中高比例的病理病例有关。欧洲目前没有可用的疫苗，针对这种虫媒病毒疾病的疫苗研究也很少。在这项研究中，我们提出了针对EHDV的新型DIVA候选疫苗，最重要的是，我们确定EHDV的VP7蛋白是一种能够诱导多血清型保护的抗原，这是针对环状病毒的疫苗研究中的主要挑战之一。
