EMD-6373

Single-particle
22.0 Å
EMD-6373 Deposition: 02/07/2015
Map released: 27/04/2016
Last modified: 04/05/2016
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-6373

JRFL Env SOSIP.664 in complex with CD4-binding site hybrid broadly neutralizing antibody DRVIA7/VRC01

EMD-6373

Single-particle
22.0 Å
EMD-6373 Deposition: 02/07/2015
Map released: 27/04/2016
Last modified: 04/05/2016
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
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
Key gp120 Glycans Pose Roadblocks to the Rapid Development of VRC01-Class Antibodies in an HIV-1-Infected Chinese Donor.
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.