ArticleImmunity2016
Key gp120 Glycans Pose Roadblocks to the Rapid Development of VRC01-Class Antibodies in an HIV-1-Infected Chinese Donor.
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Article in Immunity, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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65 citing papers in PubMed.
- Article
- Maturation of HIV-1 neutralizing antibodies in a germinal center conditional expression mouse model.PLoS pathogens · 2026Article
- A Mammalian Surface Display Platform to Optimize the Antigenicity of Viral Proteins for Vaccine Design.bioRxiv : the preprint server for biology · 2026Article
- Two cross-neutralizing antibodies isolated from a COVID-19 convalescent via single B cell sorting.Archives of virology · 2025Article
- Structural insights into VRC01-class bnAb precursors with diverse light chains elicited in the IAVI G001 human vaccine trial.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Structure and function of an unusual R452-dependent monoclonal antibody against SARS-CoV-2.Journal of virology · 2025Article
- Article
- A VRC13-like bNAb response is associated with complex escape pathways in HIV-1 envelope.Journal of virology · 2024Article
- SARS-CoV-2 hijacks neutralizing dimeric IgA for nasal infection and injury in Syrian hamstersEmerging microbes & infections · 2023Article
- Structural insights into broadly neutralizing antibodies elicited by hybrid immunity against SARS-CoV-2.Emerging microbes & infections · 2023Article
- Germline-targeting HIV-1 Env vaccination induces VRC01-class antibodies with rare insertions.Cell reports. Medicine · 2023Article
- Single-component multilayered self-assembling protein nanoparticles presenting glycan-trimmed uncleaved prefusion optimized envelope trimmers as HIV-1 vaccine candidates.Nature communications · 2023Article
- Infection with wild-type SARS-CoV-2 elicits broadly neutralizing and protective antibodies against omicron subvariants.Nature immunology · 2023Article
- Characterization of RBD-specific cross-neutralizing antibodies responses against SARS-CoV-2 variants from COVID-19 convalescents.Frontiers in immunology · 2023Article
- Bibliometric and visualized analysis of elite controllers based on CiteSpace: landscapes, hotspots, and frontiers.Frontiers in cellular and infection microbiology · 2023Article
- A SARS-CoV-2 neutralizing antibody discovery by single cell sequencing and molecular modeling.Journal of biomedical research · 2022Article
- A broadly neutralizing antibody protects Syrian hamsters against SARS-CoV-2 Omicron challenge.Nature communications · 2022Article
- Complementary Roles of Antibody Heavy and Light Chain Somatic Hypermutation in Conferring Breadth and Potency to the HIV-1-Specific CAP256-VRC26 bNAb Lineage.Journal of virology · 2022Article
- Highly mutated antibodies capable of neutralizing N276 glycan-deficient HIV after a single immunization with an Env trimer.Cell reports · 2022Article
- Structural basis of glycan276-dependent recognition by HIV-1 broadly neutralizing antibodies.Cell reports · 2021Article
5 more citing papers are in PubMed but not listed here.
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Authors and funding
28 authors.
Leopold KongDepartment of Integrative Structural and Computational Biology, The Scripps Research Insititute, La Jolla, CA 92037, USA; Scripps Center for HIV/AIDS Vaccine Immunology & Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
Bin JuState Key Laboratory for Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Changping District, Beijing 102206, China.
Yajing ChenDepartment of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
Linling HeDepartment of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
Li RenState Key Laboratory for Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Changping District, Beijing 102206, China.
Jiandong LiuState Key Laboratory for Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Changping District, Beijing 102206, China.
Kunxue HongState Key Laboratory for Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Changping District, Beijing 102206, China.
Bin SuJiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu Province 210009, China.
Zheng WangState Key Laboratory for Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Changping District, Beijing 102206, China.
Gabriel OzorowskiDepartment of Integrative Structural and Computational Biology, The Scripps Research Insititute, La Jolla, CA 92037, USA; Scripps Center for HIV/AIDS Vaccine Immunology & Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
Xiaolin JiState Key Laboratory for Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Changping District, Beijing 102206, China.
Yuanzi HuaDepartment of Integrative Structural and Computational Biology, The Scripps Research Insititute, La Jolla, CA 92037, USA; Scripps Center for HIV/AIDS Vaccine Immunology & Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
Yanli ChenState Key Laboratory for Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Changping District, Beijing 102206, China.
Marc C DellerThe Joint Center for Structural Genomics, The Scripps Research Institute, La Jolla, CA 92037, USA.
Yanling HaoState Key Laboratory for Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Changping District, Beijing 102206, China.
Yi FengState Key Laboratory for Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Changping District, Beijing 102206, China.
Fernando GarcesDepartment of Integrative Structural and Computational Biology, The Scripps Research Insititute, La Jolla, CA 92037, USA; Scripps Center for HIV/AIDS Vaccine Immunology & Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
Richard WilsonInternational AIDS Vaccine Initiative Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
Kaifan DaiDepartment of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
Sijy O'DellVaccine Research Center, NIH, Bethesda, MD 20892, USA.
Krisha McKeeVaccine Research Center, NIH, Bethesda, MD 20892, USA.
John R MascolaVaccine Research Center, NIH, Bethesda, MD 20892, USA.
Andrew B WardDepartment of Integrative Structural and Computational Biology, The Scripps Research Insititute, La Jolla, CA 92037, USA; Scripps Center for HIV/AIDS Vaccine Immunology & Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
Richard T WyattScripps Center for HIV/AIDS Vaccine Immunology & Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
Yuxing LiInstitute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20850, USA.
Ian A WilsonDepartment of Integrative Structural and Computational Biology, The Scripps Research Insititute, La Jolla, CA 92037, USA; Scripps Center for HIV/AIDS Vaccine Immunology & Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA; The Joint Center for Structural Genomics, The Scripps Research Institute, La Jolla, CA 92037, USA; Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
Jiang ZhuScripps Center for HIV/AIDS Vaccine Immunology & Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: jiang@scripps.edu.
Yiming ShaoState Key Laboratory for Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Changping District, Beijing 102206, China; Health Science Center, Peking University, Haidian District, Beijing 100191, China; School of Medicine, Nankai University, Nankai District, Tianjin 300071, China. Electronic address: yshao@bjmu.edu.cn.
Funding
Support Component D/Vaccine Discovery, Concept to ClinicUM1AI100663 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI BAROUCH, DAN H. · 2012 to 2018
$131.5MVirologyP30AI036214 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Maile Ann Young Karris · 1994 to 2026
$78.4MStructure Determination Core at SSRLU54GM094586 · NIGMS · SCRIPPS RESEARCH INSTITUTE, THE · PI WILSON, IAN A · 2010 to 2014
$40.1MStructural studies of native-like SOSIP trimersP01AI110657 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI MOORE, JOHN P · 2015 to 2024
$35.4MVirology &ImmunologyU19AI051915 · NIAID · NATIONAL CENTER FOR AIDS/STD CONTROL AND PREVENTION · PI GAO, GEORGE FU · 2002 to 2009
$21.6MNon-Human PrimatesP01AI104722 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI WYATT, RICHARD THOMAS · 2014 to 2018
$14.6MHigh-resolution definition of B cell responses to HIV Env for immunogen designR01AI102766 · NIAID · UNIV OF MARYLAND, COLLEGE PARK · PI LI, YUXING · 2013 to 2024
$6.6MStructural Biology of HIV-1 Neutralizing Antibody Targets for Vaccine DesignR01AI084817 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI WILSON, IAN A · 2009 to 2013
$3.2MStructure and dynamics of native HIV-1 envelope trimersR56AI084817 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI WILSON, IAN A · 2015 to 2015
$593kNIAID NIH HHS AI084817NIAID NIH HHS P01 AI104722NIAID NIH HHS P01 AI110657NIAID NIH HHS P30 AI036214NIAID NIH HHS P30AI36214NIAID NIH HHS R01 AI084817NIAID NIH HHS R01 AI102766NIAID NIH HHS R56 AI084817NIAID NIH HHS U19 AI051915NIAID NIH HHS U19AI51915NIAID NIH HHS UM1 AI100663NIGMS NIH HHS U54 GM094586
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.
Indexed as
Amino Acid SequenceAntibodies, MonoclonalAntibodies, NeutralizingBinding Sites, AntibodyBroadly Neutralizing AntibodiesCD4-Positive T-Lymphocytesenv Gene Products, Human Immunodeficiency VirusHIV-1HIV AntibodiesHIV Envelope Protein gp120HIV InfectionsHumansMolecular Sequence DataAntibodies, MonoclonalAntibodies, NeutralizingBroadly Neutralizing Antibodiesenv Gene Products, Human Immunodeficiency Virusgp120 protein, Human immunodeficiency virus 1gp140 envelope protein, Human immunodeficiency virus 1HIV AntibodiesHIV Envelope Protein gp120VRC01 monoclonal antibodyantibody maturationB cell developmentbroadly neutralizing antibodiesCD4-binding siteglycan shieldgp120HIV infectionrational vaccine designvirus-host co-evolutionVRC01 class
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