Vaccinia virus (VACV) A14 is a major envelope protein and a dominant antibody target in the smallpox vaccine. However, the role of anti-A14 antibodies in immunity against orthopoxviruses is unclear. Here, we characterized 22 A14 monoclonal antibodies (mAb) from two mice immunized with VACV. Epitope mapping showed that 21 mAbs targeted the C-terminal hydrophilic region, while one mAb recognized the middle region predicted to be across the viral envelope from the C-terminus. However, none of the mAbs bound to virions in studies with electron microscopy. Interestingly, some mAbs showed low VACV neutralization activities in the presence of complement and provided protection to SCID mice challenged with VACV ACAM2000. Our data showed that, although A14 is an immunodominant antigen in smallpox vaccine, its B cell epitopes are either enclosed within the virions or are inaccessible on virion surface. Anti-A14 antibodies, however, could contribute to protection against VACV through a complement-dependent pathway.

中文翻译：

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鼠痘苗病毒包膜蛋白A14的鼠抗体应答的特征揭示了缺乏有效中和靶标的免疫显性抗原。

痘苗病毒（VACV）A14是天花疫苗的主要包膜蛋白和主要抗体靶标。但是，抗A14抗体在抗正痘病毒免疫中的作用尚不清楚。在这里，我们表征了用VACV免疫的两只小鼠的22种A14单克隆抗体（mAb）。表位作图表明，有21个mAb靶向C端亲水区，而一个mAb识别了预计从C端跨过病毒被膜的中间区。但是，在电子显微镜研究中，没有单克隆抗体与病毒体结合。有趣的是，某些mAb在补体存在下显示出低的VACV中和活性，并为受到VACV ACAM2000攻击的SCID小鼠提供保护。我们的数据表明，尽管A14是天花疫苗中的一种免疫优势抗原，它的B细胞表位要么被包裹在病毒粒子内，要么无法在病毒粒子表面进入。但是，抗A14抗体可能通过补体依赖性途径帮助预防VACV。