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')2 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.

中文翻译：

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马中和免疫球蛋白和针对胡宁病毒的免疫球蛋白片段的开发。

阿根廷出血热（AHF）是一种由鼠类传播的疾病，致死率高达30％，是由新世界性鼻病毒Junin病毒（JUNV）引起的。它曾经是南美的主要流行病，并使阿根廷的数百万人处于危险之中。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，基于小鼠和马中免疫原和免疫方法之间的比较，建立了有效产生马抗血清的策略。通过给马接种带有JUNV GP假型的水疱性口炎病毒，最终获得了针对JUNV的抗血清。马抗体IgG和F（ab' ）2随后被证明可有效中和带有JUNV GP的水疱性口炎病毒假型，并显示出对病原性新世界性鼻病毒的一些交叉中和作用。进一步的研究表明，GP1上的Asp123是结合抗体的重要位点，该抗体主要针对JUNV GP1进行中和。总的来说，这项研究提出了一种开发针对JUNV的马抗血清的有效策略，并提供了GP1特异性马抗体作为AHF的潜在疗法。