Key gp120 Glycans Pose Roadblocks to the Rapid Development of VRC01-Class Antibodies in an HIV-1-Infected Chinese Donor

Kong, Leopold; Ju, Bin; Chen, Yajing; He, Linling; Ren, Li; Liu, Jiandong; Hong, Kunxue; Su, Bin; Wang, Zheng; Ozorowski, Gabriel; Ji, Xiaolin; Hua, Yuanzi; Chen, Yanli; Deller, Marc C.; Hao, Yanling; Feng, Yi; Garces, Fernando; Wilson, Richard; Dai, Kaifan; O’Dell, Sijy; McKee, Krisha; Mascola, John R.; Ward, Andrew B.; Wyatt, Richard T.; Li, Yuxing; Wilson, Ian A.; Zhu, Jiang; Shao, Yiming

doi:10.1016/j.immuni.2016.03.006

Title: Key gp120 Glycans Pose Roadblocks to the Rapid Development of VRC01-Class Antibodies in an HIV-1-Infected Chinese Donor

Journal Article · Fri Apr 01 00:00:00 EDT 2016 · Immunity

DOI:https://doi.org/10.1016/j.immuni.2016.03.006· OSTI ID:1352095

Kong, Leopold; Ju, Bin; Chen, Yajing; He, Linling; Ren, Li; Liu, Jiandong; Hong, Kunxue; Su, Bin; Wang, Zheng; Ozorowski, Gabriel; Ji, Xiaolin; Hua, Yuanzi; Chen, Yanli; Deller, Marc C.; Hao, Yanling; Feng, Yi; Garces, Fernando; Wilson, Richard; Dai, Kaifan; O’Dell, Sijy more »

VRC01-class antibodies neutralize diverse HIV-1 strains by targeting the conserved CD4-binding site. Despite extensive investigations, crucial events in the early stage of VRC01 development remain elusive. We demonstrated how VRC01-class antibodies emerged in a Chinese donor by antigen-specific single B cell sorting, structural and functional studies, and longitudinal antibody and virus repertoire analyses. A monoclonal antibody DRVIA7 with modest neutralizing breadth was isolated that displayed a subset of VRC01 signatures. X-ray and EM structures revealed a VRC01-like angle of approach, but less favorable interactions between the DRVIA7 light-chain CDR1 and the N terminus with N276 and V5 glycans of gp120. Although the DRVIA7 lineage was unable to acquire broad neutralization, longitudinal analysis revealed a repertoire-encoded VRC01 light-chain CDR3 signature and VRC01-like neutralizing heavy-chain precursors that rapidly matured within 2 years. Furthermore, light chain accommodation of the glycan shield should be taken into account in vaccine design targeting this conserved site of vulnerability.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES); NIH NIGMS; SKLID Development; NIH NIAID; NIH CIPRA

Grant/Contract Number:: AC02-06CH11357; U54 GM094586; 2012SKLID103; R01 AI102766; AI084817; P30AI36214; U19AI51915; 2012ZX10001008; UM1 AI100663; P01 AI110657

OSTI ID:: 1352095

Alternate ID(s):: OSTI ID: 1252759

Journal Information:: Immunity, Journal Name: Immunity Vol. 44 Journal Issue: 4; ISSN 1074-7613

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 70 works

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59 BASIC BIOLOGICAL SCIENCES
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Title: Key gp120 Glycans Pose Roadblocks to the Rapid Development of VRC01-Class Antibodies in an HIV-1-Infected Chinese Donor

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