Molecular and Cellular Biology Graduate Program, University of Washington and Basic Sciences Division, Fred Hutch Cancer Center, Seattle, WA 98109, USA; Basic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
Laboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital of Cologne, University of Cologne, 50931 Cologne, Germany; German Center for Infection Research, partner site Bonn-Cologne, 50931 Cologne, Germany; Department I of Internal Medicine, Faculty of Medicine and University Hospital of Cologne, University of Cologne, 50931 Cologne, Germany.
Cell Host Microbe. 2023 Jul 12;31(7):1200-1215.e9. doi: 10.1016/j.chom.2023.05.025. Epub 2023 Jun 15.
Understanding the specificities of human serum antibodies that broadly neutralize HIV can inform prevention and treatment strategies. Here, we describe a deep mutational scanning system that can measure the effects of combinations of mutations to HIV envelope (Env) on neutralization by antibodies and polyclonal serum. We first show that this system can accurately map how all functionally tolerated mutations to Env affect neutralization by monoclonal antibodies. We then comprehensively map Env mutations that affect neutralization by a set of human polyclonal sera that neutralize diverse strains of HIV and target the site engaging the host receptor CD4. The neutralizing activities of these sera target different epitopes, with most sera having specificities reminiscent of individual characterized monoclonal antibodies, but one serum targeting two epitopes within the CD4-binding site. Mapping the specificity of the neutralizing activity in polyclonal human serum will aid in assessing anti-HIV immune responses to inform prevention strategies.
了解广泛中和 HIV 的人血清抗体的特异性可以为预防和治疗策略提供信息。在这里，我们描述了一种深度突变扫描系统，该系统可以测量 HIV 包膜 (Env) 上突变组合对抗体和多克隆血清中和作用的影响。我们首先表明，该系统可以准确地描绘出所有功能上可耐受的 Env 突变对单克隆抗体中和作用的影响。然后，我们全面描绘了影响一组中和多种 HIV 株并靶向与宿主受体 CD4 结合的位点的人多克隆血清中和作用的 Env 突变。这些血清的中和活性针对不同的表位，其中大多数血清具有类似于个别特征化的单克隆抗体的特异性，但有一种血清针对 CD4 结合位点内的两个表位。描绘多克隆人血清中和活性的特异性将有助于评估抗 HIV 免疫反应，为预防策略提供信息。
