Evidence map›Paper›PMID 39823319›Full record

ArticleScience immunology2025

Anti-immune complex antibodies are elicited during repeated immunization with HIV Env immunogens.

Sharidan Brown, Aleksandar Antanasijevic, Leigh M Sewall, Daniel Montiel Garcia, James Ferguson, Philip J M Brouwer, Rogier W Sanders, Andrew B Ward

Erratum issuedAbstract read
In one paragraph

Article in Science immunology, 2025. 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 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Trial
  2. Article
  3. Article
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  5. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Sharidan BrownDepartment of Integrative, Structural and Computational Biology, Scripps Research, La Jolla, CA, USA.ORCID 0000-0002-3166-6548
Aleksandar AntanasijevicGlobal Health Institute, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Leigh M SewallDepartment of Integrative, Structural and Computational Biology, Scripps Research, La Jolla, CA, USA.ORCID 0000-0002-2020-2991
Daniel Montiel GarciaDepartment of Integrative, Structural and Computational Biology, Scripps Research, La Jolla, CA, USA.ORCID 0000-0002-5915-7016
James FergusonDepartment of Integrative, Structural and Computational Biology, Scripps Research, La Jolla, CA, USA.ORCID 0000-0003-2891-0850
Philip J M BrouwerDepartment of Integrative, Structural and Computational Biology, Scripps Research, La Jolla, CA, USA.ORCID 0000-0002-2902-7739
Rogier W SandersDepartment of Medical Microbiology, Amsterdam Institute for Infection and Immunity, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.ORCID 0000-0002-2324-8573
Andrew B WardDepartment of Integrative, Structural and Computational Biology, Scripps Research, La Jolla, CA, USA.ORCID 0000-0001-7153-3769

Funding

Identification of neutralizing epitopes on SARS-CoV-2 spike for design of vaccines and small-molecule antiviralsUM1AI144462 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI BURTON, DENNIS R. · 2019 to 2025
$201.6M
Support Component D/Vaccine Discovery, Concept to ClinicUM1AI100663 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI BURTON, DENNIS R. · 2012 to 2018
$131.5M
Pacific Northwest Center for Cryo-EM - Screening supplementU24GM129547 · NIGMS · OREGON HEALTH & SCIENCE UNIVERSITY · PI EVANS, JAMES E, GOUAUX, JAMES E · 2018 to 2023
$54.8M
Structural studies of native-like SOSIP trimersP01AI110657 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI MOORE, JOHN P · 2015 to 2024
$35.4M
Dissecting Polyclonal Sera to Reveal Correlates of Productive Immune Responses to HIVR01AI136621 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI Lars Oliver Hangartner, Andrew Barrett Ward · 2018 to 2026
$8.0M
Gates Foundation INV-002916NIAID NIH HHS P01 AI110657NIAID NIH HHS R01 AI136621NIAID NIH HHS UM1 AI100663NIAID NIH HHS UM1 AI144462NIGMS NIH HHS U24 GM129547
6 · The paper itself

Abstract

Vaccination strategies against HIV-1 aim to elicit broadly neutralizing antibodies (bnAbs) using prime-boost regimens with HIV envelope (Env) immunogens. Epitope mapping has shown that early antibody responses are directed to easily accessible nonneutralizing epitopes on Env instead of bnAb epitopes. Autologously neutralizing antibody responses appear upon boosting, once immunodominant epitopes are saturated. Here, we use electron microscopy-based polyclonal epitope mapping (EMPEM) to elucidate how repeated immunization with HIV Env SOSIP immunogens results in the generation of Ab2α anti-idiotypic antibodies in rabbits and rhesus macaques. We present the structures of six anti-immune complex antibodies and find that they target idiotopes composed of framework regions of antibodies bound to Env. Examination of cryo-electron microscopy density enabled prediction of sequences for an anti-immune complex antibody, the paratope of which is enriched with aromatic amino acids. This work sheds light on current vaccine development efforts for HIV, as well as for other pathogens in which repeated exposure to antigen is required.

Indexed as

AIDS VaccinesAntibodies, Anti-IdiotypicAntigen-Antibody Complexenv Gene Products, Human Immunodeficiency VirusHIV-1HIV AntibodiesHIV InfectionsAnimalsAntibodies, NeutralizingCryoelectron MicroscopyEpitope MappingHumansMacaca mulattaRabbitsAIDS VaccinesAntibodies, Anti-IdiotypicAntibodies, NeutralizingAntigen-Antibody Complexenv Gene Products, Human Immunodeficiency VirusHIV Antibodies

Identifiers

PMID39823319
PMCPMC12057571

What Socratic holds

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Registered trials

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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 Socratic graph.