Development of horse neutralizing immunoglobulin and immunoglobulin fragments against Junin virus
Development of horse neutralizing immunoglobulin and immunoglobulin fragments against Junin virus
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DOI：
10.1016/j.antiviral.2019.104666
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发表时间：
2020-02-01
影响因子：
7.6
通讯作者：
Xiao, Gengfu
中科院分区：
文献类型：
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作者：
Pan, Xiaoyan;Wu, Yan;Xiao, Gengfu
阿根廷出血热(AHF)是一种啮齿动物传播的疾病，致死率高达30%，由新大陆新大陆病毒Junin病毒(JUNV)引起。它曾经是南美洲的一种主要流行病，并将阿根廷数百万人置于危险之中。在这里，我们的目标是研制抗JUNV的马抗体或抗体片段。在制备马抗体之前，通过比较小鼠和马的免疫原和免疫方法，建立了一种高效产生马抗血清的策略。用携带JUNV gp的水泡性口炎病毒假型免疫马，获得抗JUNV的抗血清。随后证明，马抗体Ig G和F(ab‘)(2)能有效中和携带JUNV gp的水泡性口炎病毒假型，并对致病的新世界狂犬病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是主要针对JUNV GP1的中和抗体的重要结合位点。总而言之，这项研究提出了一种有效的策略来开发抗JUNV的马抗血清，并提供了GP1特异性的马抗体作为治疗AHF的潜在药物。
Argentine haemorrhagic fever (AHF) is a rodent-borne disease with a lethality as high as similar to 30%, which is caused by the New World arenavirus, Junin 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.