State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, China.
State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, China; University of the Chinese Academy of Sciences, Beijing, 100039, China.
Antiviral Res. 2020 Feb;174:104666. doi: 10.1016/j.antiviral.2019.104666. Epub 2019 Nov 21.
Argentine haemorrhagic fever (AHF) is a rodent-borne disease with a lethality as high as ~30%, which is caused by the New World arenavirus, Junín virus (JUNV). It was once a major epidemic in South America and puts millions of people in Argentina at risk. Here, we aimed to develop horse antibodies or antibody fragments against JUNV. Before preparing the horse antibodies, a strategy to efficiently generate horse antisera was established based on comparisons among immunogens and immunization methods in both mice and horses. Antisera against JUNV were finally obtained by vaccinating horses with vesicular stomatitis virus pseudotypes bearing JUNV GP. The horse antibodies IgG and F(ab') were subsequently demonstrated to effectively neutralize vesicular stomatitis virus pseudotypes bearing JUNV GP and to show some cross-neutralization against pathogenic New World arenaviruses. Further research revealed that Asp123 on GP1 is an important site for the binding of antibodies targeting mainly JUNV GP1 for neutralization. Collectively, this study presents an efficient strategy to develop horse antisera against JUNV and provides GP1-specific horse antibodies as potential therapeutics for AHF.
阿根廷出血热（AHF）是一种由新域丝状病毒、胡宁病毒（JUNV）引起的啮齿动物传播疾病，其致死率高达约 30%。它曾是南美洲的一次重大疫情，使阿根廷数百万人面临风险。在这里，我们旨在开发针对 JUNV 的马抗体或抗体片段。在制备马抗体之前，我们基于免疫原和免疫方法在小鼠和马中的比较，建立了一种有效产生马抗血清的策略。最后，通过用携带 JUNV GP 的水疱性口炎病毒假型对马进行疫苗接种，获得了针对 JUNV 的抗血清。随后证明马抗体 IgG 和 F(ab')可有效中和携带 JUNV GP 的水疱性口炎病毒假型，并对致病性新域丝状病毒表现出一定的交叉中和作用。进一步的研究表明，GP1 上的 Asp123 是针对主要针对 JUNV GP1 进行中和的抗体的结合的重要位点。总之，这项研究提出了一种有效开发针对 JUNV 的马抗血清的策略，并提供了作为 AHF 潜在治疗方法的 GP1 特异性马抗体。
