Evidence map›Paper›PMID 27851912›Full record

ArticleImmunity2016

Identification of a CD4-Binding-Site Antibody to HIV that Evolved Near-Pan Neutralization Breadth.

Jinghe Huang, Byong H Kang, Elise Ishida, Tongqing Zhou, Trevor Griesman, Zizhang Sheng, Fan Wu, Nicole A Doria-Rose, Baoshan Zhang, Krisha McKee and 25 more

Registry-linked trialOpen access · bronzeAbstract read
In one paragraph

Article in Immunity, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03538626 (VRC 609), which is not on this map. Cited by 281 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
281citing papers in PubMed, 1 pooled it
23.8field-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.

NCT03538626 phase1completednot on this mapstarted 2018, after this paper: background citation

VRC 609: A Phase I, Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics of a Human Monoclonal Antibody, VRC-HIVMAB091-00-AB (N6LS), Administered Intravenously or Subcutaneously With or Without Recombinant Human Hyaluronidase PH20 (rHuPH20) to Healthy Adults

TypeinterventionalSponsorNational Institute of Allergy and Infectious Diseases (NIAID)Ran2018 to 2022Enrolled33ConditionsHIV AntibodiesArmsVRC-HIVMAB091-00-AB, rHuPH20
3 · Its place in the literature

Who cites it

281 citing papers in PubMed, 1 synthesis or guideline pooled it, 388 citations in OpenAlex.

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  12. 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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221 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

35 authors at 5 institutions in 1 country.

Jinghe HuangHIV-Specific Immunity Section of the Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
Byong H KangHIV-Specific Immunity Section of the Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
Elise IshidaHIV-Specific Immunity Section of the Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
Tongqing ZhouVaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
Trevor GriesmanHIV-Specific Immunity Section of the Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
Zizhang ShengDepartment of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
Fan WuLaboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
Nicole A Doria-RoseVaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
Baoshan ZhangVaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
Krisha McKeeVaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
Sijy O'DellVaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
Gwo-Yu ChuangVaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
Aliaksandr DruzVaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
Ivelin S GeorgievDepartment of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Chaim A SchrammDepartment of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
Anqi ZhengVaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
M Gordon JoyceVaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
Mangaiarkarasi AsokanVaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
Amy RansierVaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
Sam DarkoVaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
Stephen A MiguelesHIV-Specific Immunity Section of the Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
Robert T BailerVaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
Mark K LouderVaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
S Munir AlamDuke Human Vaccine Institute, Duke University, Durham, NC 27710, USA.
Robert ParksDuke Human Vaccine Institute, Duke University, Durham, NC 27710, USA.
Garnett KelsoeDuke Human Vaccine Institute, Duke University, Durham, NC 27710, USA.
Tarra Von HolleDuke Human Vaccine Institute, Duke University, Durham, NC 27710, USA.
Barton F HaynesDuke Human Vaccine Institute, Duke University, Durham, NC 27710, USA.
Daniel C DouekVaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
Vanessa HirschLaboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
Michael S SeamanBeth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Lawrence ShapiroVaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
John R MascolaVaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
Peter D KwongVaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
Mark ConnorsHIV-Specific Immunity Section of the Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA. Electronic address: mconnors@nih.gov.
National Institute of Allergy and Infectious Diseases · USDuke University · USColumbia University · USBeth Israel Deaconess Medical Center · USVanderbilt University Medical Center · US

Funding

Neutralization Mechanisms Of Anti-HIV-1 Monoclonal AntibodiesZIAAI005022 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI ZHOU, TONGQING · 2009 to 2025
$24.6M
Mechanisms Of Immune Mediated Restriction Of HIV Replication In LTNPZIAAI000855 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI CONNORS, MARK · 2009 to 2025
$20.0M
Mechanisms of Effective Humoral Immune Responses to HIV-1ZIAAI001090 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI CONNORS, MARK · 2009 to 2025
$14.8M
Isolation of Monoclonal Antiobodies Against HIVZIAAI005095 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI DORIA-ROSE, NICOLE · 2009 to 2025
$14.5M
Vaccine Studies Of Simian Immunodeficiency Virus (SIV) in MacaquesZIAAI000686 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI HIRSCH, VANESSA M. · 2009 to 2018
$10.0M
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
Computational Tools for Structural AnalysisZICAI005112 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI RAWI, REDA · 2010 to 2025
$4.1M
Intramural NIH HHS Z99 AI999999Intramural NIH HHS ZIA AI000855Intramural NIH HHS ZIA AI001090
6 · The paper itself

Abstract

Detailed studies of the broadly neutralizing antibodies (bNAbs) that underlie the best available examples of the humoral immune response to HIV are providing important information for the development of therapies and prophylaxis for HIV-1 infection. Here, we report a CD4-binding site (CD4bs) antibody, named N6, that potently neutralized 98% of HIV-1 isolates, including 16 of 20 that were resistant to other members of its class. N6 evolved a mode of recognition such that its binding was not impacted by the loss of individual contacts across the immunoglobulin heavy chain. In addition, structural analysis revealed that the orientation of N6 permitted it to avoid steric clashes with glycans, which is a common mechanism of resistance. Thus, an HIV-1-specific bNAb can achieve potent, near-pan neutralization of HIV-1, making it an attractive candidate for use in therapy and prophylaxis.

Indexed as

Antibodies, NeutralizingAntibody SpecificityBinding Sites, AntibodyCD4-Positive T-LymphocytesCell SeparationHIV-1HIV AntibodiesHIV Envelope Protein gp120HIV InfectionsHumansAntibodies, NeutralizingHIV AntibodiesHIV Envelope Protein gp120antibodyCD4-binding siteenvelopeHIVimmunotherapyneutralizingprophylaxisresistancestructurevaccine

Identifiers

PMID27851912
PMCPMC5770152
OpenAlexW2551273870

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Registered trials

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.