Evidence map›Paper›PMID 31527908›Full record

ArticlePLoS pathogens2019

Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies.

Celia C LaBranche, Rory Henderson, Allen Hsu, Shay Behrens, Xuejun Chen, Tongqing Zhou, Kevin Wiehe, Kevin O Saunders, S Munir Alam, Mattia Bonsignori and 18 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2019. 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 56 papers.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed
5.9field-weighted citation impact, top 3% 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

56 citing papers in PubMed, 84 citations in OpenAlex.

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  4. Deletions in variable region 1 of the HIV envelope accelerate V3-glycan bNAb induction in SHIV-infected rhesus macaques.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  5. Priming of Multiple HIV Neutralizing B Cell Precursors in Humans.medRxiv : the preprint server for health sciences · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

28 authors at 5 institutions in 2 countries.

Celia C LaBrancheDepartment of Surgery, Duke University Medical Center, Durham, NC, United States of America.ORCID 0000-0002-6653-6655
Rory HendersonDuke Human Vaccine Institute, Duke University Medical Center, Durham, NC, United States of America.
Allen HsuGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC, United States of America.ORCID 0000-0003-2065-3802
Shay BehrensDepartment of Surgery, Duke University Medical Center, Durham, NC, United States of America.ORCID 0000-0001-8676-2345
Xuejun ChenVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.ORCID 0000-0001-9192-0440
Tongqing ZhouVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.ORCID 0000-0002-3935-4637
Kevin WieheDuke Human Vaccine Institute, Duke University Medical Center, Durham, NC, United States of America.
Kevin O SaundersDepartment of Surgery, Duke University Medical Center, Durham, NC, United States of America.ORCID 0000-0001-7399-7954
S Munir AlamDuke Human Vaccine Institute, Duke University Medical Center, Durham, NC, United States of America.
Mattia BonsignoriDuke Human Vaccine Institute, Duke University Medical Center, Durham, NC, United States of America.ORCID 0000-0003-2973-2101
Mario J BorgniaGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC, United States of America.ORCID 0000-0001-9159-1413
Quentin J SattentauThe Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.ORCID 0000-0001-7170-1937
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.ORCID 0000-0002-2468-8589
Hua-Xin LiaoDuke Human Vaccine Institute, Duke University Medical Center, Durham, NC, United States of America.
Wilton B WilliamsDuke Human Vaccine Institute, Duke University Medical Center, Durham, NC, United States of America.
James PeacockDuke Human Vaccine Institute, 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.
Robert J EdwardsDuke Human Vaccine Institute, Duke University Medical Center, Durham, NC, United States of America.ORCID 0000-0003-4446-1194
Thomas B KeplerDepartment of Microbiology, Boston University School of Medicine, Boston, MA, United States of America.ORCID 0000-0002-1383-6865
Bette T KorberLos Alamos National Laboratory, Theoretical Biology & Biophysics, Los Alamos, NM, 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.
Priyamvada AcharyaDepartment of Surgery, Duke University Medical Center, Durham, NC, United States of America.
Barton F HaynesDuke Human Vaccine Institute, Duke University Medical Center, Durham, NC, United States of America.
David C MontefioriDepartment of Surgery, Duke University Medical Center, Durham, NC, United States of America.ORCID 0000-0003-0856-6319
Duke Medical Center · USNational Institutes of Health · USBoston University · USLos Alamos National Laboratory · USUniversity of Oxford · GB

Funding

Virus biology scientific research support componentUM1AI100645 · NIAID · DUKE UNIVERSITY · PI MCMICHAEL, ANDREW JAMES · 2012 to 2018
$204.7M
Virus and Antibody Gene Sequencing CoreP01AI131251 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Kevin Wiehe · 2017 to 2026
$40.7M
Targeting early metastable intermediates of the SARS-CoV-2 spike for vaccine and therapeutics developmentR01AI145687 · NIAID · DUKE UNIVERSITY · PI Priyamvada Acharya · 2019 to 2026
$6.9M
Medical Research Council G0000635NIAID NIH HHS P01 AI131251NIAID NIH HHS R01 AI145687NIAID NIH HHS UM1 AI100645
6 · The paper itself

Abstract

The CD4 binding site (CD4bs) of the HIV-1 envelope glycoprotein is susceptible to multiple lineages of broadly neutralizing antibodies (bnAbs) that are attractive to elicit with vaccines. The CH235 lineage (VH1-46) of CD4bs bnAbs is particularly attractive because the most mature members neutralize 90% of circulating strains, do not possess long HCDR3 regions, and do not contain insertions and deletions that may be difficult to induce. We used virus neutralization to measure the interaction of CH235 unmutated common ancestor (CH235 UCA) with functional Env trimers on infectious virions to guide immunogen design for this bnAb lineage. Two Env mutations were identified, one in loop D (N279K) and another in V5 (G458Y), that acted synergistically to render autologous CH505 transmitted/founder virus susceptible to neutralization by CH235 UCA. Man5-enriched N-glycans provided additional synergy for neutralization. CH235 UCA bound with nanomolar affinity to corresponding soluble native-like Env trimers as candidate immunogens. A cryo-EM structure of CH235 UCA bound to Man5-enriched CH505.N279K.G458Y.SOSIP.664 revealed interactions of the antibody light chain complementarity determining region 3 (CDR L3) with the engineered Env loops D and V5. These results demonstrate that virus neutralization can directly inform vaccine design and suggest a germline targeting and reverse engineering strategy to initiate and mature the CH235 bnAb lineage.

Indexed as

AIDS VaccinesAmino Acid SubstitutionAntibody AffinityBinding SitesBroadly Neutralizing AntibodiesCD4 AntigensDrug Designenv Gene Products, Human Immunodeficiency VirusEpitopesHEK293 CellsHIV-1HIV AntibodiesHIV InfectionsHost Microbial InteractionsHumansModels, MolecularAIDS VaccinesBroadly Neutralizing AntibodiesCD4 Antigensenv Gene Products, Human Immunodeficiency VirusEpitopesHIV Antibodies

Identifiers

PMID31527908
PMCPMC6764681
OpenAlexW4246311764

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.