ArticleCell host & microbe2020
VRC34-Antibody Lineage Development Reveals How a Required Rare Mutation Shapes the Maturation of a Broad HIV-Neutralizing Lineage.
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Article in Cell host & microbe, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
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- Computing the inducibility of broadly neutralizing antibodies under a context-dependent model of affinity maturation: applications to sequential vaccine design.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
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- B cell repertoire sequencing of HIV-1 pediatric elite-neutralizers identifies multiple broadly neutralizing antibody clonotypes.Frontiers in immunology · 2024Article
- Antibody-directed evolution reveals a mechanism for enhanced neutralization at the HIV-1 fusion peptide site.Nature communications · 2023Article
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- Strategies for HIV-1 vaccines that induce broadly neutralizing antibodies.Nature reviews. Immunology · 2023Review
- Dependence on a variable residue limits the breadth of an HIV MPER neutralizing antibody, despite convergent evolution with broadly neutralizing antibodies.PLoS pathogens · 2022Article
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- Epitope-focused immunogen design based on the ebolavirus glycoprotein HR2-MPER region.PLoS pathogens · 2022Article
- Development of Neutralization Breadth against Diverse HIV-1 by Increasing Ab-Ag Interface on V2.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Broadly neutralizing antibodies target the coronavirus fusion peptide.bioRxiv : the preprint server for biology · 2022Article
- Rapid selection of HIV envelopes that bind to neutralizing antibody B cell lineage members with functional improbable mutations.Cell reports · 2021Article
- Development of Martini 2.2 parameters for N-glycans: a case study of the HIV-1 Env glycoprotein dynamics.Glycobiology · 2021Article
- Advancing HIV Broadly Neutralizing Antibodies: From Discovery to the Clinic.Frontiers in public health · 2021Review
- Neutralizing Antibodies Targeting HIV-1 gp41.Viruses · 2020Review
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Authors and funding
36 authors at 4 institutions in 2 countries.
Chen-Hsiang ShenVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Brandon J DeKoskyVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Department of Chemical & Petroleum Engineering and Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, KS 66045, USA.
Yicheng GuoDepartment of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA.
Kai XuVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Ying GuVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Divya KilamVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Sung Hee KoVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Rui KongVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Kevin LiuVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Mark K LouderVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Li OuVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Baoshan ZhangVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Cara W ChaoVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Martin M CorcoranDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Eric FengVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Jesse HuangVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Erica NormandinVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Sijy O'DellVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Amy RansierVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Reda RawiVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Mallika SastryVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Stephen D SchmidtVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Shuishu WangVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Yiran WangVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Gwo-Yu ChuangVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Nicole A Doria-RoseVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Bob LinVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Tongqing ZhouVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Eli A BoritzVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Mark ConnorsLaboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda MD 20892, USA.
Daniel C DouekVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Gunilla B Karlsson HedestamDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Zizhang ShengDepartment of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA.
Lawrence ShapiroVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA.
John R MascolaVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: jmascola@nih.gov.
Peter D KwongVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA. Electronic address: pdkwong@nih.gov.
National Institute of Allergy and Infectious Diseases · USNational Institutes of Health · USColumbia University · USKarolinska Institutet · SE
Funding
Neutralization Mechanisms Of Anti-HIV-1 Monoclonal AntibodiesZIAAI005022 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI ZHOU, TONGQING · 2009 to 2025
$24.6MQuantitative Immunological Assays to Assess HIV Antibodies and VaccinesZICAI005010 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI PIERSON, THEODORE · 2019 to 2025
$5.6MHigh-throughput, single-molecule sequence analysis of virus populations in vivoZIAAI005156 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI BORITZ, ELI · 2020 to 2025
$4.4MDesign of Antigenically-Specific Probes for Sera Analysis and MAb IsolationZICAI005111 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI ZHOU, TONGQING · 2010 to 2025
$4.3MComputational Tools for Structural AnalysisZICAI005112 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI RAWI, REDA · 2010 to 2025
$4.1MComprehensive analysis of human adaptive immune receptors to elucidate correlates of Epstein-Barr virus disease suppressionDP5OD023118 · OD · UNIVERSITY OF KANSAS LAWRENCE · PI DEKOSKY, BRANDON JAMES · 2016 to 2022
$2.2MRapid antibody screening systems to identify and engineer antiviral protectionR21AI166396 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI DEKOSKY, BRANDON JAMES · 2022 to 2023
$850kStructural basis of antibody affinity maturation by somatic hypermutationR21AI138024 · NIAID · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI SHENG, ZIZHANG · 2018 to 2019
$445kComprehensive molecular and functional analyses of anti-HIV-1 broadly neutralizing antibody repertoiresR21AI143407 · NIAID · UNIVERSITY OF KANSAS LAWRENCE · PI DEKOSKY, BRANDON JAMES, FORREST, MARCUS LAIRD · 2019 to 2020
$435kNIAID NIH HHS R21 AI138024NIAID NIH HHS R21 AI143407NIAID NIH HHS R21 AI166396NIH HHS DP5 OD023118Swedish Research Council
Abstract
Rare mutations have been proposed to restrict the development of broadly neutralizing antibodies against HIV-1, but this has not been explicitly demonstrated. We hypothesized that such rare mutations might be identified by comparing broadly neutralizing and non-broadly neutralizing branches of an antibody-developmental tree. Because sequences of antibodies isolated from the fusion peptide (FP)-targeting VRC34-antibody lineage suggested it might be suitable for such rare mutation analysis, we carried out next-generation sequencing (NGS) on B cell transcripts from donor N123, the source of the VRC34 lineage, and functionally and structurally characterized inferred intermediates along broadly neutralizing and poorly neutralizing developmental branches. The broadly neutralizing VRC34.01 branch required the rare heavy-chain mutation Y33P to bind FP, whereas the early bifurcated VRC34.05 branch did not require this rare mutation and evolved less breadth. Our results demonstrate how a required rare mutation can restrict development and shape the maturation of a broad HIV-1-neutralizing antibody lineage.
Indexed as
B-LymphocytesAntibodies, NeutralizingBroadly Neutralizing AntibodiesCrystallography, X-Rayenv Gene Products, Human Immunodeficiency VirusGene ExpressionHIV-1HIV AntibodiesHIV InfectionsHumansMutationTranscriptomeViral Fusion ProteinsAntibodies, NeutralizingBroadly Neutralizing Antibodiesenv Gene Products, Human Immunodeficiency VirusHIV AntibodiesViral Fusion Proteinsantibody maturationantibody sequencingB cell ontogenybroadly neutralizing antibodyfusion peptide-directedrare mutationsSHMsomatic hypermutation
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