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一种针对裂谷热和蓝舌病的二价保护性疫苗。

A protective bivalent vaccine against Rift Valley fever and bluetongue.

作者信息

Calvo-Pinilla Eva, Marín-López Alejandro, Moreno Sandra, Lorenzo Gema, Utrilla-Trigo Sergio, Jiménez-Cabello Luis, Benavides Julio, Nogales Aitor, Blasco Rafael, Brun Alejandro, Ortego Javier

机构信息

Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Centro de Investigación en Sanidad Animal (INIA-CISA), Madrid, Spain.

Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT USA.

出版信息

NPJ Vaccines. 2020 Jul 30;5(1):70. doi: 10.1038/s41541-020-00218-y. eCollection 2020.

DOI:10.1038/s41541-020-00218-y
PMID:32793399
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7393076/
Abstract

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.

摘要

裂谷热（RVF）和蓝舌病（BT）是两种由节肢动物传播的重要反刍动物疾病。这两种病毒均呈现出重要的地理扩散，导致蓝舌病病毒（BTV）在非洲和欧洲地方流行。在本研究中，我们报道了一种双价疫苗，该疫苗基于表达BTV蛋白VP2、NS1或截短形式的NS1（NS1-Nt）以及RVFV Gn和Gc糖蛋白的改良安卡拉痘苗病毒（MVA），可同时诱导针对BTV和RVFV的保护性免疫反应。用两剂MVA-GnGc-VP2免疫的IFNAR小鼠产生了针对BTV-4和RVFV的显著中和抗体反应。此外，用MVA-GnGc-NS1或MVA-GnGc-NS1-Nt进行同源初免-加强免疫在小鼠中引发了针对RVFV的中和抗体以及NS1特异性细胞毒性CD8 + T细胞。而且，所有用MVA-GnGc-NS1或MVA-GnGc-NS1-Nt免疫的小鼠在受到RVFV或BTV-4致死性攻击后均保持健康。在绵羊中检测了用MVA-GnGc-NS1进行的同源初免-加强疫苗接种，这是在小鼠中观察到的最佳免疫策略。在用BTV-4或RVFV攻击后，接种疫苗的绵羊没有出现临床症状或病毒血症，或者病毒血症大幅降低。这些结果表明，MVA-GnGc-NS1疫苗接种可在绵羊中引发针对RVFV和BTV的免疫保护。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3764/7393076/390cedd2c835/41541_2020_218_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3764/7393076/390cedd2c835/41541_2020_218_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3764/7393076/390cedd2c835/41541_2020_218_Fig1_HTML.jpg

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Vector competence is strongly affected by a small deletion or point mutations in bluetongue virus.
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Vaccine candidates based on MVA viral vectors expressing VP2 or VP7 confer full protection against Epizootic hemorrhagic disease virus in IFNAR(-/-) mice.基于表达VP2或VP7的改良痘苗病毒安卡拉（MVA）病毒载体的候选疫苗，可在干扰素α/β受体基因敲除（IFNAR(-/-)）小鼠中提供针对流行性出血病病毒的完全保护。
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