Journal
SCIENCE ADVANCES
Volume 6, Issue 38, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abb1328
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Funding
- National Major Project [2012ZX10001008, 2018ZX10731101-001-019]
- National Postdoctoral Program for Innovative Talents [BX201600078]
- State Key Laboratory Innovative Project [2012SKLID103]
- International AIDS Vaccine Initiative Neutralizing Antibody Center
- CAVD [OPP1196345]
- HIV Vaccine Research and Design (HIVRAD) program [P01 AI124337]
- NIH [R01 AI129698, R01 AI140844, R01 AI43563]
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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 438-611 and 438-D5 were isolated that potently neutralize HIV-1 with moderate breadth, are encoded by the V(H)1-69 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.
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