Journal: Immunity / Year: 2016 Title: Key gp120 Glycans Pose Roadblocks to the Rapid Development of VRC01-Class Antibodies in an HIV-1-Infected Chinese Donor. Authors: Leopold Kong / Bin Ju / Yajing Chen / Linling He / Li Ren / Jiandong Liu / Kunxue Hong / Bin Su / Zheng Wang / Gabriel Ozorowski / Xiaolin Ji / Yuanzi Hua / Yanli Chen / Marc C Deller / ...Authors: Leopold Kong / Bin Ju / Yajing Chen / Linling He / Li Ren / Jiandong Liu / Kunxue Hong / Bin Su / Zheng Wang / Gabriel Ozorowski / Xiaolin Ji / Yuanzi Hua / Yanli Chen / Marc C Deller / Yanling Hao / Yi Feng / Fernando Garces / Richard Wilson / Kaifan Dai / Sijy O'Dell / Krisha McKee / John R Mascola / Andrew B Ward / Richard T Wyatt / Yuxing Li / Ian A Wilson / Jiang Zhu / Yiming Shao / 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 ...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.
Mass: 39211.434 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human immunodeficiency virus 1 / Gene: Env / Cell line (production host): HEK 293S / Production host: Homo sapiens (human) / References: UniProt: A0A0M3KKW9*PLUS
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Antibody , 2 types, 2 molecules CD
#2: Antibody
DRVIA7FabHeavyChain
Mass: 24048.031 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): HEK 293F / Production host: Homo sapiens (human)
#3: Antibody
DRVIA7FabLightChain
Mass: 23207.871 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): HEK 293F / Production host: Homo sapiens (human)