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, M. C. Hao, Y. Feng, Y. Garces, F. Wilson, R. Dai, K. O'Dell, S. McKee, K. Mascola, J. R. Ward, Andrew Wyatt, Richard Li, Y. Wilson, Ian Zhu, Jiang Shao, Y.Source
Immunity 2016 44:939-950Url
- Early-stage development of a VRC01-class antibody in a Chinese HIV patient
VRC01-class heavy chains can evolve within 2 years
- VRC01-class light-chain CDR3 signature is encoded within the B cell repertoire
Light-chain N terminus and CDR1 conformation need to accommodate key gp120 glycans
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.
B cell Repertoire Analysis