EMD-6373
JRFL Env SOSIP.664 in complex with CD4-binding site hybrid broadly neutralizing antibody DRVIA7/VRC01
EMD-6373
Single-particle22.0 Å
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Map released: 27/04/2016
Last modified: 04/05/2016
Sample Organism:
Human immunodeficiency virus 1,
Homo sapiens
Sample: Fab of broadly neutralizing antibody hybrid DRVIA7/VRC01 in complex with HIV-1 JRFL Env SOSIP.664 trimer
Deposition Authors: Ozorowski G, Ward AB
Sample: Fab of broadly neutralizing antibody hybrid DRVIA7/VRC01 in complex with HIV-1 JRFL Env SOSIP.664 trimer
Deposition Authors: Ozorowski G, Ward AB
Key gp120 Glycans Pose Roadblocks to the Rapid Development of VRC01-Class Antibodies in an HIV-1-Infected Chinese Donor.
Kong L
,
Ju B
,
Chen Y,
He L,
Ren L,
Liu J,
Hong K,
Su B,
Wang Z,
Ozorowski G,
Ji X,
Hua Y,
Chen Y,
Deller MC
,
Hao Y,
Feng Y,
Garces F,
Wilson R,
Dai K,
O'Dell S,
McKee K,
Mascola JR,
Ward AB,
Wyatt RT,
Li Y,
Wilson IA,
Zhu J,
Shao Y
(2016) Immunity , 44 , 939 - 950
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(2016) Immunity , 44 , 939 - 950
Abstract:
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. Thus, light chain accommodation of the glycan shield should be taken into account in vaccine design targeting this conserved site of vulnerability.
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. Thus, light chain accommodation of the glycan shield should be taken into account in vaccine design targeting this conserved site of vulnerability.