A protective bivalent vaccine against Rift Valley fever and bluetongue
A protective bivalent vaccine against Rift Valley fever and bluetongue
复制标题
DOI：
10.1038/s41541-020-00218-y
复制
发表时间：
2020-07-30
期刊：
影响因子：
9.2
通讯作者：
Ortego, Javier
中科院分区：
文献类型：
--
作者：
Calvo-Pinilla, Eva;Marin-Lopez, Alejandro;Ortego, Javier
裂谷热(RVF)和蓝舌病(Bt)是由节肢动物传播的两种重要反刍动物疾病。这两种病毒都显示出重要的地理传播，导致Bt病毒(BTV)在非洲和欧洲流行。在这项工作中，我们报道了一种双重疫苗，该疫苗基于表达BTV蛋白VP2、NS1或NS1截断形式(NS1-NT)的改良痘苗病毒(MVA)以及RVFV Gn和GC糖蛋白，同时诱导对BTV和RVFV的保护性免疫应答。用两种剂量的MVA-GnGc-VP2免疫IFNAR(-/-)小鼠后，小鼠对BTV-4和RVFV产生明显的中和抗体应答。此外，MVA-GnGc-NS1或MVA-GnGc-NS1-NT的同源初始加强免疫可在小鼠体内触发针对RVFV和NS1特异性细胞毒CD8+T细胞的中和抗体。此外，MVA-GnGc-NS1或MVA-GnGc-NS1-NT免疫的小鼠在RVFV或BTV-4致死攻击后仍保持健康。用绵羊进行了MVA-GnGc-NS1的同源加强免疫，这是在小鼠中观察到的最好的免疫策略。BTV-4或RVFV攻击后，免疫绵羊的临床症状消失或病毒血症显著减轻。这些结果表明，MVA-GnGc-NS1疫苗对绵羊RVFV和BTV具有免疫保护作用。
Rift Valley fever (RVF) and bluetongue (BT) are two important ruminant diseases transmitted by arthropods. Both viruses have shown important geographic spread leading to endemicity of BT virus (BTV) in Africa and Europe. In this work, we report a dual vaccine that simultaneously induces protective immune responses against BTV and RVFV based on modified vaccinia Ankara virus (MVA) expressing BTV proteins VP2, NS1, or a truncated form of NS1 (NS1-Nt), and RVFV Gn and Gc glycoproteins. IFNAR((-/-))mice immunized with two doses of MVA-GnGc-VP2 developed a significant neutralizing antibody response against BTV-4 and RVFV. Furthermore, the homologous prime-boost immunization with MVA-GnGc-NS1 or MVA-GnGc-NS1-Nt triggered neutralizing antibodies against RVFV and NS1-specific cytotoxic CD8+ T cells in mice. Moreover, all mice immunized with MVA-GnGc-NS1 or MVA-GnGc-NS1-Nt remained healthy after lethal challenge with RVFV or BTV-4. The homologous prime-boost vaccination with MVA-GnGc-NS1, which was the best immunization strategy observed in mice, was assayed in sheep. Clinical signs and viremia were absent or highly reduced in vaccinated sheep after challenge with BTV-4 or RVFV. These results indicate that MVA-GnGc-NS1 vaccination elicits immune protection against RVFV and BTV in sheep.