T-6 Theoretical Biology & Biophysics, Los Alamos National Laboratory, Los Alamos, New Mexico.
Departments of Medicine & Microbiology, University of Pennsylvania, Pennsylvania.
Curr Opin HIV AIDS. 2020 Sep;15(5):267-274. doi: 10.1097/COH.0000000000000639.
The surface of the HIV-1 Env glycoprotein, the target of neutralizing antibodies, is extensively covered by N-linked glycans that create a glycan shield. Broadly neutralizing antibodies (bNAbs), the primary targets of HIV-1 vaccine design, have to negotiate this glycan shield. Here, we review the barriers and opportunities that the HIV-1 glycan shield presents for vaccine induction of bNAbs.
Glycan shields can impact the nature of the antibody response and influence the development of neutralization breadth in HIV-1 infections. The architecture of the glycan shield arising from glycan interactions and dynamics have been modeled, and its fine structure, that is, the site-wise glycan heterogeneity, has been determined for some isolates. Although the extent of glycan shielding is conserved, the precise number, location and processing of glycans, however, is strain-dependent. New insights continue to reveal how such differences can impact bNAb activity and development. Novel approaches have exploited the glycan shield for designing immunogens that bind the germline precursors of bNAbs, a critical roadblock for vaccine-induction of bNAbs.
The HIV-1 glycan shield can significantly impact the induction and maturation of bNAbs, and a better understanding of how to manipulate it will improve immunogen design.
HIV-1 包膜糖蛋白（Env）的表面被大量的 N 连接聚糖覆盖，形成聚糖屏蔽。广泛中和抗体（bnAbs）是 HIV-1 疫苗设计的主要目标，必须克服这种聚糖屏蔽。在这里，我们综述了 HIV-1 聚糖屏蔽对疫苗诱导 bnAbs 所带来的挑战和机遇。
聚糖屏蔽可以影响抗体反应的性质，并影响 HIV-1 感染中中和广度的发展。已经对聚糖相互作用和动力学引起的聚糖屏蔽结构进行了建模，并且已经确定了一些分离株的精细结构，即逐点聚糖异质性。尽管聚糖屏蔽的程度是保守的，但糖基的精确数量、位置和加工方式取决于毒株。新的见解不断揭示这些差异如何影响 bnAb 的活性和发展。新方法利用聚糖屏蔽设计免疫原，这些免疫原可以结合 bnAb 的胚系前体，这是疫苗诱导 bnAb 的一个关键障碍。
HIV-1 聚糖屏蔽可以显著影响 bnAbs 的诱导和成熟，更好地理解如何操纵它将有助于改进免疫原设计。
