Evidence map›Paper›PMID 26687358›Full record

ArticleCell2015

Immunogenicity of Stabilized HIV-1 Envelope Trimers with Reduced Exposure of Non-neutralizing Epitopes.

Steven W de Taeye, Gabriel Ozorowski, Alba Torrents de la Peña, Miklos Guttman, Jean-Philippe Julien, Tom L G M van den Kerkhof, Judith A Burger, Laura K Pritchard, Pavel Pugach, Anila Yasmeen and 21 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 298 papers.

0numbers the graph read from it
0cells of the map it votes in
298citing 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

298 citing papers in PubMed.

  1. Trial
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  3. Priming of Multiple HIV Neutralizing B Cell Precursors in Humans.medRxiv : the preprint server for health sciences · 2026
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238 more citing papers are in PubMed but not listed here.

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

31 authors.

Steven W de TaeyeDepartment of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam 1105 AZ, the Netherlands.
Gabriel OzorowskiDepartment of Integrative Structural and Computational Biology, Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
Alba Torrents de la PeñaDepartment of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam 1105 AZ, the Netherlands.
Miklos GuttmanDepartment of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA.
Jean-Philippe JulienDepartment of Integrative Structural and Computational Biology, Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
Tom L G M van den KerkhofDepartment of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam 1105 AZ, the Netherlands; Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam 1105 AZ, the Netherlands.
Judith A BurgerDepartment of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam 1105 AZ, the Netherlands.
Laura K PritchardOxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
Pavel PugachDepartment of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021, USA.
Anila YasmeenDepartment of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021, USA.
Jordan CramptonDivision of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, Center for HIV-1/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID), La Jolla, CA 92037, USA.
Joyce HuDivision of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, Center for HIV-1/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID), La Jolla, CA 92037, USA.
Ilja BontjerDepartment of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam 1105 AZ, the Netherlands.
Jonathan L TorresDepartment of Integrative Structural and Computational Biology, Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
Heather ArendtInternational AIDS Vaccine Initiative, New York, NY 10004, USA.
Joanne DeStefanoInternational AIDS Vaccine Initiative, New York, NY 10004, USA.
Wayne C KoffInternational AIDS Vaccine Initiative, New York, NY 10004, USA.
Hanneke SchuitemakerDepartment of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam 1105 AZ, the Netherlands.
Dirk EgginkDepartment of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam 1105 AZ, the Netherlands.
Ben BerkhoutDepartment of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam 1105 AZ, the Netherlands.
Hansi DeanInternational AIDS Vaccine Initiative, New York, NY 10004, USA.
Celia LaBrancheDepartment of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Shane CrottyDivision of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, Center for HIV-1/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID), La Jolla, CA 92037, USA.
Max CrispinOxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
David C MontefioriDepartment of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
P J KlasseDepartment of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021, USA.
Kelly K LeeDepartment of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA.
John P MooreDepartment of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021, USA.
Ian A WilsonDepartment of Integrative Structural and Computational Biology, Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, CA 92037, USA; The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Andrew B WardDepartment of Integrative Structural and Computational Biology, Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
Rogier W SandersDepartment of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam 1105 AZ, the Netherlands; Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021, USA. Electronic address: r.w.sanders@amc.uva.nl.

Funding

Support Component D/Vaccine Discovery, Concept to ClinicUM1AI100663 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI CRISPIN, MAX · 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
Trimer Production and Immunogenicity TestingP01AI082362 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI MOORE, JOHN P · 2009 to 2014
$16.0M
Biophysical Signatures in HIV-1 Env Correlating with Mother-to-Child TransmissionR21AI112389 · NIAID · UNIVERSITY OF WASHINGTON · PI LEE, KELLY KEISEN · 2014 to 2015
$471k
NIAID NIH HHS P01 AI082362NIAID NIH HHS P01 AI110657NIAID NIH HHS P01 AI82362NIAID NIH HHS R21 AI112389NIAID NIH HHS R21AI112389NIAID NIH HHS UM1 AI100663
6 · The paper itself

Abstract

The envelope glycoprotein trimer mediates HIV-1 entry into cells. The trimer is flexible, fluctuating between closed and more open conformations and sometimes sampling the fully open, CD4-bound form. We hypothesized that conformational flexibility and transient exposure of non-neutralizing, immunodominant epitopes could hinder the induction of broadly neutralizing antibodies (bNAbs). We therefore modified soluble Env trimers to stabilize their closed, ground states. The trimer variants were indeed stabilized in the closed conformation, with a reduced ability to undergo receptor-induced conformational changes and a decreased exposure of non-neutralizing V3-directed antibody epitopes. In rabbits, the stabilized trimers induced similar autologous Tier-1B or Tier-2 NAb titers to those elicited by the corresponding wild-type trimers but lower levels of V3-directed Tier-1A NAbs. Stabilized, closed trimers might therefore be useful components of vaccines aimed at inducing bNAbs.

Indexed as

AIDS VaccinesAnimalsAntibodies, Neutralizingenv Gene Products, Human Immunodeficiency VirusEpitopesHIV-1HIV Envelope Protein gp41Hydrophobic and Hydrophilic InteractionsImmunoglobulin GModels, MolecularMutagenesisProtein ConformationRabbitsAIDS VaccinesAntibodies, Neutralizingenv Gene Products, Human Immunodeficiency VirusEpitopesHIV Envelope Protein gp41Immunoglobulin G

Identifiers

PMID26687358
PMCPMC4732737

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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.