Evidence map›Paper›PMID 26949186›Full record

ArticleCell2016

Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a CD4-Mimic Antibody.

Mattia Bonsignori, Tongqing Zhou, Zizhang Sheng, Lei Chen, Feng Gao, M Gordon Joyce, Gabriel Ozorowski, Gwo-Yu Chuang, Chaim A Schramm, Kevin Wiehe and 42 more

Open access · bronzeAbstract read
In one paragraph

Article in Cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 241 papers.

0numbers the graph read from it
0cells of the map it votes in
241citing papers in PubMed
27.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

241 citing papers in PubMed, 326 citations in OpenAlex.

  1. Trial
  2. Trial
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  4. Article
  5. Priming of Multiple HIV Neutralizing B Cell Precursors in Humans.medRxiv : the preprint server for health sciences · 2026
    Article
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  18. Review
  19. Review
  20. Explore antibody repertoire in the era of AI.Acta biochimica et biophysica Sinica · 2025
    Article

181 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

52 authors at 11 institutions in 1 country.

Mattia BonsignoriDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.
Tongqing ZhouVaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Zizhang ShengDepartment of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Department of Systems Biology, Columbia University, New York, NY 10032, USA.
Lei ChenVaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Feng GaoDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.
M Gordon JoyceVaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Gabriel OzorowskiDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
Gwo-Yu ChuangVaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Chaim A SchrammDepartment of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Department of Systems Biology, Columbia University, New York, NY 10032, USA.
Kevin WieheDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.
S Munir AlamDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.
Todd BradleyDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Morgan A GladdenDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Kwan-Ki HwangDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Sheelah IyengarDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Amit KumarDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Xiaozhi LuDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Kan LuoDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Michael C MangiapaniDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Robert J ParksDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Hongshuo SongDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Priyamvada AcharyaVaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Robert T BailerVaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Allen CaoVaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Aliaksandr DruzVaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Ivelin S GeorgievVaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA; Department of Electrical Engineering and Computer Science, Vanderbilt University, Nashville, TN 37232, USA; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA.
Young D KwonVaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Mark K LouderVaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Baoshan ZhangVaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Anqi ZhengVaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Brenna J HillVaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Rui KongVaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Cinque SotoVaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
NISC Comparative Sequencing Program
James C MullikinNIH Intramural Sequencing Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Daniel C DouekVaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
David C MontefioriDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Surgery, Duke University School of Medicine, Durham, NC 27710, USA; Department of Pediatrics, Duke University School of Medicine, Durham, NC 27710, USA; Department of Immunology, Duke University School of Medicine, Durham, NC 27710, USA.
Michael A MoodyDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Pediatrics, Duke University School of Medicine, Durham, NC 27710, USA; Department of Immunology, Duke University School of Medicine, Durham, NC 27710, USA.
George M ShawDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Beatrice H HahnDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Garnett KelsoeDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Immunology, Duke University School of Medicine, Durham, NC 27710, USA.
Peter T HraberLos Alamos National Laboratory, Los Alamos, NM 87544, USA.
Bette T KorberLos Alamos National Laboratory, Los Alamos, NM 87544, USA.
Scott D BoydDepartment of Pathology, Stanford School of Medicine, Palo Alto, CA 94305, USA.
Andrew Z FireDepartment of Pathology, Stanford School of Medicine, Palo Alto, CA 94305, USA.
Thomas B KeplerDepartment of Microbiology, Boston University, Boston, MA 02118, USA; Department of Mathematics and Statistics, Boston University, Boston, MA 02118, USA.
Lawrence ShapiroVaccine Research Center, National Institutes 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; Department of Systems Biology, Columbia University, New York, NY 10032, USA.
Andrew B WardDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
John R MascolaVaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Hua-Xin LiaoDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.
Peter D KwongVaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: pdkwong@nih.gov.
Barton F HaynesDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA; Department of Immunology, Duke University School of Medicine, Durham, NC 27710, USA; Duke Global Health Institute, Duke University School of Medicine, Durham, NC 27710, USA. Electronic address: barton.haynes@duke.edu.
Duke University · USNational Institutes of Health · USNational Institute of Allergy and Infectious Diseases · USColumbia University · USLos Alamos National Laboratory · USScripps Research Institute · USStanford Medicine · USUniversity of Pennsylvania · USBoston University · USDuke Institute for Health Innovation · USNational Human Genome Research Institute · US

Funding

Virus biology scientific research support componentUM1AI100645 · NIAID · DUKE UNIVERSITY · PI MCMICHAEL, ANDREW JAMES · 2012 to 2018
$204.7M
Inter- and Intra-Species Comparative SequencingZIBHG000196 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI THOMAS, JAMES · 2009 to 2025
$177.6M
Support Component D/Vaccine Discovery, Concept to ClinicUM1AI100663 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI BAROUCH, DAN H. · 2012 to 2018
$131.5M
Virus & Reservoirs CoreP30AI045008 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI ROBERT GROSS · 1999 to 2026
$78.6M
Neutralization Mechanisms Of Anti-HIV-1 Monoclonal AntibodiesZIAAI005022 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI ZHOU, TONGQING · 2009 to 2025
$24.6M
Host Genomic Factors in Infectious Disease Susceptibility ZIAAI005066 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI DOUEK, DANIEL CESAR · 2009 to 2025
$17.9M
Non-Human PrimatesP01AI104722 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI WYATT, RICHARD THOMAS · 2014 to 2018
$14.6M
T Cell Immune Responses To HIV And Other PathogensZIAAI005033 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI DOUEK, DANIEL CESAR · 2009 to 2025
$11.4M
The HIV ReservoirZIAAI005034 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI DOUEK, DANIEL CESAR · 2009 to 2025
$7.5M
Design of Antigenically-Specific Probes for Sera Analysis and MAb IsolationZICAI005111 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI ZHOU, TONGQING · 2010 to 2025
$4.3M
Rational Immunogen Design Using Computational MethodsZICAI005114 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI RAWI, REDA · 2010 to 2025
$4.3M
Computational Algorithms, Methods, and Tools for Structure-Based Vaccine DesignZICAI005113 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI KWONG, PETER D · 2010 to 2019
$2.5M
Intramural NIH HHS ZIA AI005022NIAID NIH HHS P01 AI104722NIAID NIH HHS P01-AI104722NIAID NIH HHS P30 AI045008NIAID NIH HHS UM1 AI100645NIAID NIH HHS UM1 AI100663
6 · The paper itself

Abstract

Antibodies with ontogenies from VH1-2 or VH1-46-germline genes dominate the broadly neutralizing response against the CD4-binding site (CD4bs) on HIV-1. Here, we define with longitudinal sampling from time-of-infection the development of a VH1-46-derived antibody lineage that matured to neutralize 90% of HIV-1 isolates. Structures of lineage antibodies CH235 (week 41 from time-of-infection, 18% breadth), CH235.9 (week 152, 77%), and CH235.12 (week 323, 90%) demonstrated the maturing epitope to focus on the conformationally invariant portion of the CD4bs. Similarities between CH235 lineage and five unrelated CD4bs lineages in epitope focusing, length-of-time to develop breadth, and extraordinary level of somatic hypermutation suggested commonalities in maturation among all CD4bs antibodies. Fortunately, the required CH235-lineage hypermutation appeared substantially guided by the intrinsic mutability of the VH1-46 gene, which closely resembled VH1-2. We integrated our CH235-lineage findings with a second broadly neutralizing lineage and HIV-1 co-evolution to suggest a vaccination strategy for inducing both lineages.

Indexed as

AIDS VaccinesAmino Acid SequenceAntibodies, NeutralizingB-LymphocytesHIV-1HIV AntibodiesHIV Envelope Protein gp120HIV InfectionsHumansModels, MolecularMolecular Sequence DataSequence AlignmentAIDS VaccinesAntibodies, Neutralizinggp120 protein, Human immunodeficiency virus 1HIV AntibodiesHIV Envelope Protein gp120

Identifiers

PMID26949186
PMCPMC4826291
OpenAlexW2289942604

What OpenQuestion holds

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LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.