Evidence map›Paper›PMID 30395637›Full record

ArticlePLoS pathogens2018

HIV-1 envelope glycan modifications that permit neutralization by germline-reverted VRC01-class broadly neutralizing antibodies.

Celia C LaBranche, Andrew T McGuire, Matthew D Gray, Shay Behrens, Peter D Kwong, Xuejun Chen, Tongqing Zhou, Quentin J Sattentau, James Peacock, Amanda Eaton and 11 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
2.9field-weighted citation impact, top 9% 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

38 citing papers in PubMed, 48 citations in OpenAlex.

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  7. 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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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors at 6 institutions in 2 countries.

Celia C LaBrancheDepartment of Surgery, Duke University Medical Center, Durham, NC, United States of America.ORCID 0000-0002-6653-6655
Andrew T McGuireFred Hutchinson Cancer Research Center, Department of Global Health, Seattle, WA, United States of America.
Matthew D GrayFred Hutchinson Cancer Research Center, Department of Global Health, Seattle, WA, United States of America.ORCID 0000-0002-4260-9784
Shay BehrensDepartment of Surgery, Duke University Medical Center, Durham, NC, United States of America.ORCID 0000-0001-8676-2345
Peter D Kwong
Xuejun ChenVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Tongqing ZhouVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Quentin J SattentauThe Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, United Kingdom.ORCID 0000-0001-7170-1937
James PeacockDuke University School of Medicine, Departments of Medicine and Immunology, Duke Human Vaccine Institute, Durham, NC, United States of America.
Amanda EatonDepartment of Surgery, Duke University Medical Center, Durham, NC, United States of America.
Kelli GreeneDepartment of Surgery, Duke University Medical Center, Durham, NC, United States of America.
Hongmei GaoDepartment of Surgery, Duke University Medical Center, Durham, NC, United States of America.
Haili TangDepartment of Surgery, Duke University Medical Center, Durham, NC, United States of America.
Lautaro G PerezDepartment of Surgery, Duke University Medical Center, Durham, NC, United States of America.
Xuejun Chen
Kevin O SaundersDepartment of Surgery, Duke University Medical Center, Durham, NC, United States of America.
Peter D KwongVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
John R MascolaVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Barton F HaynesDuke University School of Medicine, Departments of Medicine and Immunology, Duke Human Vaccine Institute, Durham, NC, United States of America.
Leonidas StamatatosFred Hutchinson Cancer Research Center, Department of Global Health, Seattle, WA, United States of America.ORCID 0000-0002-1106-7097
David C MontefioriDepartment of Surgery, Duke University Medical Center, Durham, NC, United States of America.ORCID 0000-0003-0856-6319
Duke Medical Center · USDuke University · USFred Hutch Cancer Center · USNational Institutes of Health · USUniversity of Oxford · GBUniversity of Washington · US

Funding

LOC: HIV Vaccine Trials NetworkUM1AI068614 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Dan H. Barouch, Lawrence Corey · 2011 to 2026
$1175.6M
Virus and Antibody Gene Sequencing CoreP01AI131251 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Kevin Wiehe · 2017 to 2026
$40.7M
Design Of ImmunogensZIAAI005024 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI ZHOU, TONGQING · 2009 to 2025
$21.5M
Defining BCR evolution during immunizationR01AI104384 · NIAID · SEATTLE BIOMEDICAL RESEARCH INSTITUTE · PI STAMATATOS, LEONIDAS · 2013 to 2021
$5.9M
Monitoring the development of anti-Env Abs during HIV infectionR01AI081625 · NIAID · SEATTLE BIOMEDICAL RESEARCH INSTITUTE · PI STAMATATOS, LEONIDAS · 2010 to 2020
$5.8M
Medical Research Council G0000635NIAID NIH HHS P01 AI131251NIAID NIH HHS R01 AI081625NIAID NIH HHS R01 AI104384NIAID NIH HHS UM1 AI068614
6 · The paper itself

Abstract

Broadly neutralizing antibody (bnAb) induction is a high priority for effective HIV-1 vaccination. VRC01-class bnAbs that target the CD4 binding site (CD4bs) of trimeric HIV-1 envelope (Env) glycoprotein spikes are particularly attractive to elicit because of their extraordinary breadth and potency of neutralization in vitro and their ability to protect against infection in animal models. Glycans bordering the CD4bs impede the binding of germline-reverted forms of VRC01-class bnAbs and therefore constitute a barrier to early events in initiating the correct antibody lineages. Deleting a subset of these glycans permits Env antigen binding but not virus neutralization, suggesting that additional barriers impede germline-reverted VRC01-class antibody binding to functional Env trimers. We investigated the requirements for functional Env trimer engagement of VRC01-class naïve B cell receptors by using virus neutralization and germline-reverted antibodies as surrogates for the interaction. Targeted deletion of a subset of N-glycans bordering the CD4bs, combined with Man5 enrichment of remaining N-linked glycans that are otherwise processed into larger complex-type glycans, rendered HIV-1 426c Env-pseudotyped virus (subtype C, transmitted/founder) highly susceptible to neutralization by near germline forms of VRC01-class bnAbs. Neither glycan modification alone rendered the virus susceptible to neutralization. The potency of neutralization in some cases rivaled the potency of mature VRC01 against wildtype viruses. Neutralization by the germline-reverted antibodies was abrogated by the known VRC01 resistance mutation, D279K. These findings improve our understanding of the restrictions imposed by glycans in eliciting VRC01-class bnAbs and enable a neutralization-based strategy to monitor vaccine-elicited early precursors of this class of bnAbs.

Indexed as

Antibodies, MonoclonalAntibodies, NeutralizingBinding SitesB-LymphocytesBroadly Neutralizing AntibodiesCD4 Antigensenv Gene Products, Human Immunodeficiency VirusEpitopesGlycosylationHIV-1HIV AntibodiesHIV Envelope Protein gp120HIV InfectionsHIV SeropositivityHumansPolysaccharidesAntibodies, MonoclonalAntibodies, NeutralizingBroadly Neutralizing AntibodiesCD4 Antigensenv Gene Products, Human Immunodeficiency VirusEpitopesHIV AntibodiesHIV Envelope Protein gp120PolysaccharidesVRC01 monoclonal antibody

Identifiers

PMID30395637
PMCPMC6237427
OpenAlexW2899705789

What OpenQuestion holds

Textmetadata
LicenceCC0
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.