Enhancing glycan occupancy of soluble HIV-1 envelope trimers to mimic the native viral spike

增强可溶性 HIV-1 包膜三聚体的聚糖占有率,以模拟天然病毒刺突

阅读:1
作者:Ronald Derking, Joel D Allen, Christopher A Cottrell, Kwinten Sliepen, Gemma E Seabright, Wen-Hsin Lee, Yoann Aldon, Kimmo Rantalainen, Aleksandar Antanasijevic, Jeffrey Copps, Anila Yasmeen, Albert Cupo, Victor M Cruz Portillo, Meliawati Poniman, Niki Bol, Patricia van der Woude, Steven W de Taeye,

Abstract

Artificial glycan holes on recombinant Env-based vaccines occur when a potential N-linked glycosylation site (PNGS) is under-occupied, but not on their viral counterparts. Native-like SOSIP trimers, including clinical candidates, contain such holes in the glycan shield that induce strain-specific neutralizing antibodies (NAbs) or non-NAbs. To eliminate glycan holes and mimic the glycosylation of native BG505 Env, we replace all 12 NxS sequons on BG505 SOSIP with NxT. All PNGS, except N133 and N160, are nearly fully occupied. Occupancy of the N133 site is increased by changing N133 to NxS, whereas occupancy of the N160 site is restored by reverting the nearby N156 sequon to NxS. Hence, PNGS in close proximity, such as in the N133-N137 and N156-N160 pairs, affect each other's occupancy. We further apply this approach to improve the occupancy of several Env strains. Increasing glycan occupancy should reduce off-target immune responses to vaccine antigens.

特别声明

1、本文转载旨在传播信息,不代表本网站观点,亦不对其内容的真实性承担责任。

2、其他媒体、网站或个人若从本网站转载使用,必须保留本网站注明的“来源”,并自行承担包括版权在内的相关法律责任。

3、如作者不希望本文被转载,或需洽谈转载稿费等事宜,请及时与本网站联系。

4、此外,如需投稿,也可通过邮箱info@biocloudy.com与我们取得联系。