Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Curr Opin HIV AIDS. 2013 Sep;8(5):382-92. doi: 10.1097/COH.0b013e328363a90e.
The HIV-1 site of binding for the CD4 receptor has long attracted attention as a potential supersite of vulnerability to antibody-mediated neutralization. We review recent findings related to effective CD4-binding site antibodies isolated from HIV-1-infected individuals and discuss implications for immunogen design.
Highly effective CD4-binding site antibodies such as antibody VRC01 have the ability to neutralize over 90% of circulating HIV-1 strains. Sequence and structural analysis of these antibodies from over half a dozen HIV-1-infected donors reveals remarkable similarity in their ontogenies and their modes of recognition, all of which involve mimicry of CD4 receptor by antibody-heavy chain. Meanwhile, other effective CD4-binding site neutralizers such as antibody CH103 have been shown to utilize a different mode of recognition, with next-generation sequencing of both virus and antibody suggesting co-evolution to drive the development of antibody-neutralization breadth.
The nexus of information concerning the CD4-binding site and its recognition by human antibodies capable of effective neutralization has expanded remarkably in the last few years. Although barriers are substantial, new insights from donor-serum responses, atomic-level structures of antibody-Env complexes, and next-generation sequencing of B-cell transcripts are invigorating vaccine-design efforts to elicit effective CD4-binding site antibodies.
目的综述：长期以来，HIV-1 上与 CD4 受体结合的部位一直是人们关注的焦点，被认为是潜在的易于被抗体中和的超位点。我们综述了近期从 HIV-1 感染者中分离出的有效 CD4 结合位点抗体的相关发现，并讨论了其对免疫原设计的意义。
最近的发现：高度有效的 CD4 结合位点抗体，如 VRC01 抗体，具有中和超过 90%循环 HIV-1 株的能力。来自六个以上 HIV-1 感染者供体的这些抗体的序列和结构分析揭示了它们在起源和识别模式上的显著相似性，所有这些都涉及抗体重链对 CD4 受体的模拟。同时，其他有效的 CD4 结合位点中和抗体，如 CH103 抗体，已被证明利用不同的识别模式，对病毒和抗体的下一代测序表明共同进化推动了抗体中和广度的发展。
总结：在过去的几年中，有关 CD4 结合位点及其被能够有效中和的人类抗体识别的信息网络已经显著扩展。尽管存在障碍，但来自供体血清反应、抗体-Env 复合物的原子水平结构以及 B 细胞转录本的下一代测序的新见解正在激发有效的 CD4 结合位点抗体的疫苗设计努力。
