Centre for Biological Sciences and Institute for Life Sciences, University of Southampton, Southampton SO17 1BJ, U.K.
Amsterdam Infection and Immunity Institute (AI&II), Laboratory of Experimental Virology, Department of Medical Microbiology, Academic Medical Center of the University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
Biochem Soc Trans. 2018 Jun 19;46(3):691-698. doi: 10.1042/BST20170394. Epub 2018 May 21.
The extensive post-translational modifications of the envelope spikes of the human immunodeficiency virus (HIV) present considerable challenges and opportunities for HIV vaccine design. These oligomeric glycoproteins typically have over 30 disulfide bonds and around a 100 N-linked glycosylation sites, and are functionally dependent on protease cleavage within the secretory system. The resulting mature structure adopts a compact fold with the vast majority of its surface obscured by a protective shield of glycans which can be targeted by broadly neutralizing antibodies (bnAbs). Despite the notorious heterogeneity of glycosylation, rare B-cell lineages can evolve to utilize and cope with viral glycan diversity, and these structures therefore present promising targets for vaccine design. The latest generation of recombinant envelope spike mimetics contains re-engineered post-translational modifications to present stable antigens to guide the development of bnAbs by vaccination.
人类免疫缺陷病毒（HIV）包膜刺突的广泛翻译后修饰给 HIV 疫苗设计带来了巨大的挑战和机遇。这些寡聚糖蛋白通常具有超过 30 个二硫键和约 100 个 N 连接糖基化位点，并且在功能上依赖于分泌系统内的蛋白酶切割。成熟结构采用紧凑的折叠，其大部分表面被糖基化的保护屏蔽所掩盖，这些糖基化可以被广泛中和抗体（bnAb）靶向。尽管糖基化存在明显的异质性，但罕见的 B 细胞谱系可以进化为利用和应对病毒糖基化多样性，因此这些结构为疫苗设计提供了有希望的靶标。最新一代的重组包膜刺突模拟物包含了经过重新设计的翻译后修饰，以提供稳定的抗原，通过接种疫苗来指导 bnAb 的产生。
