Evidence map›Paper›PMID 30728245›Full record

ArticleThe Journal of biological chemistry2019

Stabilization of the V2 loop improves the presentation of V2 loop-associated broadly neutralizing antibody epitopes on HIV-1 envelope trimers.

Steven W de Taeye, Eden P Go, Kwinten Sliepen, Alba Torrents de la Peña, Kimberly Badal, Max Medina-Ramírez, Wen-Hsin Lee, Heather Desaire, Ian A Wilson, John P Moore and 2 more

Abstract read
In one paragraph

Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing 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

15 citing papers in PubMed.

  1. Trial
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  10. Conformational diversity facilitates antibody mutation trajectories and discrimination between foreign and self-antigens.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  11. Article
  12. Article
  13. Article
  14. Specific Substitutions in Region V2 of gp120Pathogens (Basel, Switzerland) · 2020
    Article
  15. 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

12 authors.

Steven W de TaeyeFrom the Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam, 1105 AZ, The Netherlands.
Eden P Gothe Department of Chemistry, University of Kansas, Lawrence, Kansas 66045.
Kwinten SliepenFrom the Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam, 1105 AZ, The Netherlands.
Alba Torrents de la PeñaFrom the Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam, 1105 AZ, The Netherlands.
Kimberly BadalFrom the Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam, 1105 AZ, The Netherlands.
Max Medina-RamírezFrom the Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam, 1105 AZ, The Netherlands.
Wen-Hsin Leethe Department of Integrative Structural and Computational Biology, Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery, The Scripps Research Institute, La Jolla, California 92037, and.ORCID 0000-0001-9445-6671
Heather Desairethe Department of Chemistry, University of Kansas, Lawrence, Kansas 66045.
Ian A Wilsonthe Department of Integrative Structural and Computational Biology, Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery, The Scripps Research Institute, La Jolla, California 92037, and.
John P Moorethe Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York 10021.
Andrew B Wardthe Department of Integrative Structural and Computational Biology, Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery, The Scripps Research Institute, La Jolla, California 92037, and.
Rogier W SandersFrom the Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam, 1105 AZ, The Netherlands, r.w.sanders@amc.uva.nl.

Funding

Support Component D/Vaccine Discovery, Concept to ClinicUM1AI100663 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI BAROUCH, DAN H. · 2012 to 2018
$131.5M
Structural studies of native-like SOSIP trimersP01AI110657 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI MOORE, JOHN P · 2015 to 2024
$35.4M
NIAID NIH HHS P01 AI110657
6 · The paper itself

Abstract

A successful HIV-1 vaccine will likely need to elicit broadly neutralizing antibodies (bNAbs) that target the envelope glycoprotein (Env) spike on the virus. Native-like recombinant Env trimers of the SOSIP design now serve as a platform for achieving this challenging goal. However, SOSIP trimers usually do not bind efficiently to the inferred germline precursors of bNAbs (gl-bNAbs). We hypothesized that the inherent flexibilities of the V1 and V2 variable loops in the Env trimer contribute to the poor recognition of gl-bNAb epitopes at the trimer apex that extensively involve V2 residues. To reduce local V2 flexibility and improve the binding of V2-dependent bNAbs and gl-bNAbs, we designed BG505 SOSIP.664 trimer variants containing newly created disulfide bonds intended to stabilize the V2 loop in an optimally antigenic configuration. The first variant, I184C/E190C, contained a new disulfide bond within the V2 loop, whereas the second variant, E153C/R178C, had a new disulfide bond that cross-linked V2 and V1. The resulting engineered native-like trimer variants were both more reactive with and were neutralized by V2 bNAbs and gl-bNAbs, a finding that may be valuable in the design of germline targeting and boosting trimer immunogens to create an antigenic conformation optimal for HIV vaccine development.

Indexed as

AIDS VaccinesAntibodies, Neutralizingenv Gene Products, Human Immunodeficiency VirusEpitopesHIV-1HIV AntibodiesProtein MultimerizationProtein Structure, SecondaryAIDS VaccinesAntibodies, Neutralizingenv Gene Products, Human Immunodeficiency VirusEpitopesHIV Antibodiesantibodyglycoprotein structureHIV-1 envelope glycoprotein trimerhuman immunodeficiency virus (HIV)protein designstructure-functionvaccine development

Identifiers

PMID30728245
PMCPMC6462529

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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 OpenQuestion graph.