当前位置: X-MOL 学术Sci. Adv. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
A VH1-69 antibody lineage from an infected Chinese donor potently neutralizes HIV-1 by targeting the V3 glycan supersite.
Science Advances ( IF 13.6 ) Pub Date : 2020-09-16 , DOI: 10.1126/sciadv.abb1328
Sonu Kumar 1, 2, 3 , Bin Ju 4, 5 , Benjamin Shapero 1 , Xiaohe Lin 1 , Li Ren 4 , Lei Zhang 1 , Dan Li 4 , Zehua Zhou 5 , Yi Feng 4 , Cindy Sou 1 , Colin J Mann 1 , Yanling Hao 4 , Anita Sarkar 1, 2, 3 , Jiali Hou 4 , Christian Nunnally 1 , Kunxue Hong 4 , Shuo Wang 4 , Xiangyang Ge 4 , Bin Su 6 , Elise Landais 2, 7, 8 , Devin Sok 2, 3, 7, 8 , Michael B Zwick 7 , Linling He 1 , Jiang Zhu 1 , Ian A Wilson 1, 2, 3, 9 , Yiming Shao 4, 5, 10
Affiliation  

An oligomannose patch around the V3 base of HIV-1 envelope glycoprotein (Env) is recognized by multiple classes of broadly neutralizing antibodies (bNAbs). Here, we investigated the bNAb response to the V3 glycan supersite in an HIV-1–infected Chinese donor by Env-specific single B cell sorting, structural and functional studies, and longitudinal analysis of antibody and virus repertoires. Monoclonal antibodies 438-B11 and 438-D5 were isolated that potently neutralize HIV-1 with moderate breadth, are encoded by the VH1-69 germline gene, and have a disulfide-linked long HCDR3 loop. Crystal structures of Env-bound and unbound antibodies revealed heavy chain–mediated recognition of the glycan supersite with a unique angle of approach and a critical role of the intra-HCDR3 disulfide. The mechanism of viral escape was examined via single-genome amplification/sequencing and glycan mutations around the N332 supersite. Our findings further emphasize the V3 glycan supersite as a prominent target for Env-based vaccine design.

更新日期:2020-09-16
down
wechat
bug