Evidence map›Paper›PMID 40412376›Full record

ArticleStructure (London, England : 1993)2025

Acquisition of quaternary trimer interaction as a key step in the lineage maturation of a broad and potent HIV-1 neutralizing antibody.

Qingbo Liu, Ruth J Parsons, Kevin Wiehe, Robert J Edwards, Kevin O Saunders, Peng Zhang, Huiyi Miao, Kedamawit Tilahun, Julia Jones, Yue Chen and 9 more

Abstract read
In one paragraph

Article in Structure (London, England : 1993), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Priming of Multiple HIV Neutralizing B Cell Precursors in Humans.medRxiv : the preprint server for health sciences · 2026
    Article
  2. Article
  3. 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

19 authors.

Qingbo LiuLaboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: liu_qingbo@outlook.com.
Ruth J ParsonsDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Biochemistry , Duke University School of Medicine, Durham, NC 27710, USA.
Kevin WieheDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.
Robert J EdwardsDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Kevin O SaundersDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Surgery, Duke University School of Medicine, Durham, NC 27710, USA; Department of Integrative Immunobiology, Duke University School of Medicine, Durham, NC 27710, USA; Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710, USA.
Peng ZhangLaboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Huiyi MiaoLaboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Kedamawit TilahunDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Julia JonesDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Yue ChenDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Bhavna HoraDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Wilton B WilliamsDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Surgery, Duke University School of Medicine, Durham, NC 27710, USA; Department of Integrative Immunobiology, Duke University School of Medicine, Durham, NC 27710, USA.
David EasterhoffDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Xiao HuangDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Katarzyna JanowskaDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Katayoun MansouriDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Barton F HaynesDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA; Department of Integrative Immunobiology, Duke University School of Medicine, Durham, NC 27710, USA. Electronic address: barton.haynes@duke.edu.
Priyamvada AcharyaDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Biochemistry , Duke University School of Medicine, Durham, NC 27710, USA; Department of Surgery, Duke University School of Medicine, Durham, NC 27710, USA. Electronic address: priyamvada.acharya@duke.edu.
Paolo LussoLaboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: plusso@niaid.nih.gov.

Funding

Nonhuman primate studies for development of a prototype HIV vaccine that induces broadly neutralizing antibodiesUM1AI144371 · NIAID · DUKE UNIVERSITY · PI HAYNES, BARTON F. · 2019 to 2025
$190.4M
Virus and Antibody Gene Sequencing CoreP01AI131251 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Kevin Wiehe · 2017 to 2026
$40.7M
Project 3 - Dynamics of latent HIV-1 reservoirs: High resolution antigenic mapping and strategies to block reboundU54AI170752 · NIAID · DUKE UNIVERSITY · PI Priyamvada Acharya · 2022 to 2026
$32.0M
Structure-Function Studies of the HIV-1 Envelope Glycoproteins and Development of VLP-forming vaccine strategies for HIV-1ZIAAI001197 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI LUSSO, PAOLO · 2014 to 2025
$16.8M
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
Data commons for 'omic, microscopy and analysis core facilitiesS10OD018164 · OD · DUKE UNIVERSITY · PI WRAY, GREGORY A. · 2014 to 2014
$598k
Intramural NIH HHS ZIA AI001197NIAID NIH HHS P01 AI131251NIAID NIH HHS R01 AI145687NIAID NIH HHS U54 AI170752NIAID NIH HHS UM1 AI144371NIH HHS S10 OD018164
6 · The paper itself

Abstract

Although most broadly neutralizing antibodies (bNAbs) specific for the CD4-binding site (CD4-BS) of HIV-1 interact with a single gp120 protomer, a few mimic the quaternary binding mode of CD4, making contact with a second protomer through elongated heavy chain framework 3 (FRH3) or complementarity-determining region 1 (CDRH1) loops. Here, we show that a CDRH3-dominated anti-CD4-BS bNAb, CH103, establishes quaternary interaction despite regular-length FRH3 and CDRH1. This quaternary interaction is critical for neutralization and is primarily mediated by two FRH3 acidic residues that were sequentially acquired and subjected to strong positive selection during CH103 maturation. Cryoelectron microscopy (cryo-EM) structures confirmed the role of the two FRH3 acidic residues in mediating quaternary contact and demonstrated that CH103 reaches the adjacent gp120 protomer by virtue of its unique angle of approach. Thus, the acquisition of quaternary interaction may constitute a key step in the lineage maturation of a broad and potent HIV-1 neutralizing antibody.

Indexed as

Antibodies, NeutralizingHIV-1HIV AntibodiesHIV Envelope Protein gp120CD4 AntigensComplementarity Determining RegionsCryoelectron MicroscopyHumansModels, MolecularProtein BindingProtein MultimerizationAntibodies, NeutralizingCD4 AntigensComplementarity Determining Regionsgp120 protein, Human immunodeficiency virus 1HIV AntibodiesHIV Envelope Protein gp120affinity maturationCD4-binding siteenvelope trimerHIV-1lineage evolutionneutralizing antibodiesquaternary interactionunmutated common ancestorvaccine development

Identifiers

PMID40412376
PMCPMC12335366

What OpenQuestion holds

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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.