Evidence map›Paper›PMID 33453152›Full record

ArticleImmunity2021

Vaccination induces maturation in a mouse model of diverse unmutated VRC01-class precursors to HIV-neutralizing antibodies with >50% breadth.

Xuejun Chen, Tongqing Zhou, Stephen D Schmidt, Hongying Duan, Cheng Cheng, Gwo-Yu Chuang, Ying Gu, Mark K Louder, Bob C Lin, Chen-Hsiang Shen and 9 more

Open access · bronzeAbstract read
In one paragraph

Article in Immunity, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed
6.3field-weighted citation impact, top 2% 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

62 citing papers in PubMed, 66 citations in OpenAlex.

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  8. Recurrent mutations drive rapid HIV escape from two broadly neutralizing antibodies in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  16. Antibody feedback establishes an affinity brake in the germinal center.bioRxiv : the preprint server for biology · 2025
    Article
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2 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

19 authors at 6 institutions in 1 country.

Xuejun ChenVaccine 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.
Stephen D SchmidtVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Hongying DuanVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Cheng ChengVaccine 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.
Ying GuVaccine 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.
Bob C LinVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Chen-Hsiang ShenVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Zizhang ShengZuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA.
Michelle X ZhengVaccine 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.
M Gordon JoyceVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
Lawrence ShapiroVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
Ming TianProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Howard Hughes Medical Institute, Boston, MA 02115, USA.
Frederick W AltProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Howard Hughes Medical Institute, Boston, MA 02115, USA.
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.
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.
National Institutes of Health · USNational Institute of Allergy and Infectious Diseases · USColumbia University · USBoston Children's Hospital · USHoward Hughes Medical Institute · USWalter Reed Army Institute of Research · US

Funding

Virus biology scientific research support componentUM1AI100645 · NIAID · DUKE UNIVERSITY · PI HARRISON, STEPHEN COPLAN · 2012 to 2018
$204.7M
Design Of ImmunogensZIAAI005024 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI ZHOU, TONGQING · 2009 to 2025
$21.5M
HIV/AIDS Vaccine and Antibody DevelopmentZICAI005002 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI CHENG, CHENG · 2019 to 2025
$17.6M
Non-Human PrimatesP01AI104722 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI WYATT, RICHARD THOMAS · 2014 to 2018
$14.6M
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
Structural basis of antibody affinity maturation by somatic hypermutationR21AI138024 · NIAID · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI SHENG, ZIZHANG · 2018 to 2019
$445k
NIAID NIH HHS P01 AI104722NIAID NIH HHS R21 AI138024NIAID NIH HHS UM1 AI100645
6 · The paper itself

Abstract

Vaccine elicitation of broadly neutralizing antibodies (bnAbs) is a key HIV-research goal. The VRC01 class of bnAbs targets the CD4-binding site on the HIV-envelope trimer and requires extensive somatic hypermutation (SHM) to neutralize effectively. Despite substantial progress, vaccine-induced VRC01-class antibodies starting from unmutated precursors have exhibited limited neutralization breadth, particularly against viruses bearing glycan on loop D residue N276 (glycan276), present on most circulating strains. Here, using sequential immunization of immunoglobulin (Ig)-humanized mice expressing diverse unmutated VRC01-class antibody precursors, we elicited serum responses capable of neutralizing viruses bearing glycan276 and isolated multiple lineages of VRC01-class bnAbs, including two with >50% breadth on a 208-strain panel. Crystal structures of representative bnAbs revealed the same mode of recognition as known VRC01-class bnAbs. Structure-function studies further pinpointed key mutations and correlated their induction with specific immunizations. VRC01-class bnAbs can thus be matured by sequential immunization from unmutated ancestors to >50% breadth, and we delineate immunogens and regimens inducing key SHM.

Indexed as

AIDS VaccinesAnimalsB-LymphocytesBroadly Neutralizing AntibodiesDisease Models, AnimalHEK293 CellsHIV-1HIV AntibodiesHIV InfectionsHumansLymphocyte ActivationMiceMice, TransgenicMutationSomatic Hypermutation, ImmunoglobulinVaccinationAIDS VaccinesBroadly Neutralizing AntibodiesHIV Antibodiesantibody VRC01broadly neutralizing antibodyglyan276HIV-1 vaccinesomatic hypermutation

Identifiers

PMID33453152
PMCPMC8020832
OpenAlexW3118878231

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Registered trials

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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.