Evidence map›Paper›PMID 26516768›Full record

ArticlePLoS pathogens2015

A New Glycan-Dependent CD4-Binding Site Neutralizing Antibody Exerts Pressure on HIV-1 In Vivo.

Natalia T Freund, Joshua A Horwitz, Lilian Nogueira, Stuart A Sievers, Louise Scharf, Johannes F Scheid, Anna Gazumyan, Cassie Liu, Klara Velinzon, Ariel Goldenthal and 7 more

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
3.8field-weighted citation impact, top 6% 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

42 citing papers in PubMed, 54 citations in OpenAlex.

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  6. Structural Immunology of SARS-CoV-2.Immunological reviews · 2025
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  15. Article
  16. Antibodies: what makes us stronger.Human vaccines & immunotherapeutics · 2021
    Article
  17. Article
  18. Review
  19. Article
  20. Review
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

17 authors at 7 institutions in 3 countries.

Natalia T FreundLaboratory of Molecular Immunology, The Rockefeller University, New York, New York, United States of America.
Joshua A HorwitzLaboratory of Molecular Immunology, The Rockefeller University, New York, New York, United States of America.
Lilian NogueiraLaboratory of Molecular Immunology, The Rockefeller University, New York, New York, United States of America.
Stuart A SieversDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, California, United States of America.
Louise ScharfDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, California, United States of America.
Johannes F ScheidLaboratory of Molecular Immunology, The Rockefeller University, New York, New York, United States of America.
Anna GazumyanLaboratory of Molecular Immunology, The Rockefeller University, New York, New York, United States of America.
Cassie LiuLaboratory of Molecular Immunology, The Rockefeller University, New York, New York, United States of America.
Klara VelinzonLaboratory of Molecular Immunology, The Rockefeller University, New York, New York, United States of America.
Ariel GoldenthalRagon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, United States of America.
Rogier W SandersDepartment of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
John P MooreDepartment of Microbiology and Immunology, Weill Medical College, Cornell University, New York, New York, United States of America.
Pamela J BjorkmanDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, California, United States of America.
Michael S SeamanCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
Bruce D WalkerRagon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, United States of America; Howard Hughes Medical Institute, Chevy Chase, Maryland, United States of America.
Florian KleinFirst Department of Internal Medicine, University Hospital of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), University of Cologne, Germany.
Michel C NussenzweigLaboratory of Molecular Immunology, The Rockefeller University, New York, New York, United States of America; Howard Hughes Medical Institute, Chevy Chase, Maryland, United States of America.
Rockefeller University · USCalifornia Institute of Technology · USRagon Institute of MGH, MIT and Harvard · USBeth Israel Deaconess Medical Center · USCornell University · USUniversity Hospital Cologne · DEUniversity of Amsterdam · NL

Funding

Support Component D/Vaccine Discovery, Concept to ClinicUM1AI100663 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI BAROUCH, DAN H. · 2012 to 2018
$131.5M
Stuctural basis of bNab activityP01AI100148 · NIAID · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI Pamela J Bjorkman · 2013 to 2026
$43.3M
Structural studies of native-like SOSIP trimersP01AI110657 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI MOORE, JOHN P · 2015 to 2024
$35.4M
Howard Hughes Medical InstituteNIAID NIH HHS 1 P01 AI100148NIAID NIH HHS P01 AI100148NIAID NIH HHS P01 AI110657NIAID NIH HHS UM1 AI100663
6 · The paper itself

Abstract

The CD4 binding site (CD4bs) on the envelope glycoprotein is a major site of vulnerability that is conserved among different HIV-1 isolates. Many broadly neutralizing antibodies (bNAbs) to the CD4bs belong to the VRC01 class, sharing highly restricted origins, recognition mechanisms and viral escape pathways. We sought to isolate new anti-CD4bs bNAbs with different origins and mechanisms of action. Using a gp120 2CC core as bait, we isolated antibodies encoded by IGVH3-21 and IGVL3-1 genes with long CDRH3s that depend on the presence of the N-linked glycan at position-276 for activity. This binding mode is similar to the previously identified antibody HJ16, however the new antibodies identified herein are more potent and broad. The most potent variant, 179NC75, had a geometric mean IC80 value of 0.42 μg/ml against 120 Tier-2 HIV-1 pseudoviruses in the TZM.bl assay. Although this group of CD4bs glycan-dependent antibodies can be broadly and potently neutralizing in vitro, their in vivo activity has not been tested to date. Here, we report that 179NC75 is highly active when administered to HIV-1-infected humanized mice, where it selects for escape variants that lack a glycan site at position-276. The same glycan was absent from the virus isolated from the 179NC75 donor, implying that the antibody also exerts selection pressure in humans.

Indexed as

AnimalsAntibodies, NeutralizingBinding SitesCD4 AntigensHEK293 CellsHIV-1HIV AntibodiesHumansMicePolysaccharidesAntibodies, NeutralizingCD4 AntigensHIV AntibodiesPolysaccharides

Identifiers

PMID26516768
PMCPMC4627763
OpenAlexW2150999673

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.