Hitting the sweet spot: exploiting HIV-1 glycan shield for induction of broadly neutralizing antibodies.
Hitting the sweet spot: exploiting HIV-1 glycan shield for induction of broadly neutralizing antibodies.
复制标题
击中甜蜜点：利用HIV-1聚糖屏蔽诱导广泛中和抗体。
DOI：
10.1097/coh.0000000000000639
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发表时间：
2020-09
影响因子：
4.1
通讯作者：
Korber B
中科院分区：
文献类型：
--
作者：
Wagh K;Hahn BH;Korber B
中和抗体的靶标HIV-1 Env糖蛋白的表面被n -连接的聚糖广泛覆盖，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，必须通过这种聚糖屏蔽。在这里，我们回顾了HIV-1聚糖屏蔽为疫苗诱导bNAbs提供的障碍和机会。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。由聚糖相互作用和动力学引起的聚糖屏蔽结构已经建模，其精细结构，即位点上的聚糖异质性，已经确定了一些分离物。虽然聚糖屏蔽的程度是保守的，但聚糖的精确数量、位置和处理是依赖于菌株的。新的见解继续揭示这些差异如何影响bNAb的活动和发展。新的方法利用聚糖屏蔽来设计结合bNAbs种系前体的免疫原，这是疫苗诱导bNAbs的关键障碍。HIV-1聚糖屏蔽可以显著影响bNAbs的诱导和成熟，更好地了解如何操纵它将改进免疫原设计。
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, i.e. the site-wise glycan heterogeneity, have been determined for some isolates. While 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.