The Sir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, UK.
The Sir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, UK; Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Oxford OX1 3TA, UK.
Trends Microbiol. 2022 Sep;30(9):866-881. doi: 10.1016/j.tim.2022.02.004. Epub 2022 Mar 9.
Glycans are repeating carbohydrate structures added as post-translational modifications (PTMs) to proteins, forming glycoproteins. Self-glycans found on human cells, and viral glycoproteins produced in host cells, are generally weakly immunogenic, which is necessary to avoid autoimmunity. This feature is exploited by many pathogenic viruses, which glycosylate surface proteins to evade or reduce immune recognition. The HIV type-1 (HIV-1) envelope glycoprotein (Env) is heavily glycosylated, which broadly acts to shield neutralisation-relevant protein surfaces with immunorecessive self-glycans to hinder B cell recognition. However, a small subset of HIV-1-infected individuals develops potent broadly neutralising antibodies (bnAbs), many of which directly engage the glycan shield. This provides hope that such antibodies could be elicited via vaccination and help to provide protective immunity. However, HIV-1 vaccine candidates have thus far failed to fully recapitulate such glycan-specific neutralising responses. In this review we consider the fundamental glycoimmunology and structural biology that underpin glycans in antibody evasion and as antibody targets and discuss potential approaches to harness glycan targeting for HIV-1 vaccine design.
聚糖是作为翻译后修饰（PTMs）添加到蛋白质上的重复碳水化合物结构，形成糖蛋白。人类细胞自身的糖链和宿主细胞中产生的病毒糖蛋白通常免疫原性较弱，这对于避免自身免疫是必要的。这一特性被许多致病病毒所利用，它们通过糖基化表面蛋白来逃避或减少免疫识别。HIV-1 包膜糖蛋白（Env）高度糖基化，广泛地用免疫抑制性自身糖来屏蔽中和相关的蛋白表面，以阻碍 B 细胞的识别。然而，一小部分 HIV-1 感染个体产生了强大的广谱中和抗体（bnAbs），其中许多抗体直接与糖罩结合。这为通过疫苗接种引发此类抗体提供了希望，并有助于提供保护性免疫。然而，HIV-1 疫苗候选物迄今为止未能完全再现这种糖特异性中和反应。在这篇综述中，我们考虑了基础糖免疫学和结构生物学，这些学科支撑了糖在抗体逃避和作为抗体靶标中的作用，并讨论了利用糖靶向来设计 HIV-1 疫苗的潜在方法。
