Crispin Max, Ward Andrew B, Wilson Ian A
Centre for Biological Sciences and Institute for Life Sciences, University of Southampton, Southampton SO17 1BJ, United Kingdom; email:
Department of Integrative Structural and Computational Biology, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, International AIDS Vaccine Initiative Neutralizing Antibody Center, and Collaboration for AIDS Vaccine Discovery, The Scripps Research Institute, La Jolla, California 92037, USA; email:
Annu Rev Biophys. 2018 May 20;47:499-523. doi: 10.1146/annurev-biophys-060414-034156. Epub 2018 Mar 29.
Vaccine design efforts against the human immunodeficiency virus (HIV) have been greatly stimulated by the observation that many infected patients eventually develop highly potent broadly neutralizing antibodies (bnAbs). Importantly, these bnAbs have evolved to recognize not only the two protein components of the viral envelope protein (Env) but also the numerous glycans that form a protective barrier on the Env protein. Because Env is heavily glycosylated compared to host glycoproteins, the glycans have become targets for the antibody response. Therefore, considerable efforts have been made in developing and validating biophysical methods to elucidate the complex structure of the Env-spike glycoprotein, with its combination of glycan and protein epitopes. We illustrate here how the application of robust biophysical methods has transformed our understanding of the structure and function of the HIV Env spike and stimulated innovation in vaccine design strategies that takes into account the essential glycan components.
观察发现许多感染人类免疫缺陷病毒（HIV）的患者最终会产生高效的广谱中和抗体（bnAbs），这极大地推动了针对该病毒的疫苗设计工作。重要的是，这些bnAbs不仅进化到能够识别病毒包膜蛋白（Env）的两种蛋白质成分，还能识别在Env蛋白上形成保护屏障的众多聚糖。由于与宿主糖蛋白相比，Env高度糖基化，聚糖已成为抗体反应的靶点。因此，人们在开发和验证生物物理方法以阐明Env刺突糖蛋白的复杂结构（其聚糖和蛋白质表位的组合）方面付出了巨大努力。我们在此说明强大的生物物理方法的应用如何改变了我们对HIV Env刺突的结构和功能的理解，并激发了考虑到基本聚糖成分的疫苗设计策略的创新。
