Department of Microbiology, Immunology and Molecular Genetics, Long School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Division of Vaccine Discovery La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
Virology. 2018 May;518:284-292. doi: 10.1016/j.virol.2018.03.005. Epub 2018 Mar 17.
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.
痘苗病毒（VACV）A14 是一种主要的包膜蛋白，也是天花疫苗中的主要抗体靶标。然而，抗 A14 抗体在对抗正痘病毒中的作用尚不清楚。在这里，我们从两只用 VACV 免疫的小鼠中鉴定了 22 种 A14 单克隆抗体（mAb）。表位作图显示，21 种 mAb 靶向 C 末端亲水区域，而一种 mAb 识别预测从 C 末端穿过病毒包膜的中间区域。然而，在用电子显微镜研究时，没有一种 mAb 与病毒粒子结合。有趣的是，一些 mAb 在补体存在的情况下显示出对 VACV 的低中和活性，并为接受 ACAM2000 挑战的 SCID 小鼠提供保护。我们的数据表明，尽管 A14 是天花疫苗中的免疫优势抗原，但它的 B 细胞表位要么包含在病毒粒子内部，要么在病毒粒子表面无法接触。然而，抗 A14 抗体可以通过补体依赖途径促进对 VACV 的保护。
