Evidence map›Paper›PMID 26372963›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2015

Design and structure of two HIV-1 clade C SOSIP.664 trimers that increase the arsenal of native-like Env immunogens.

Jean-Philippe Julien, Jeong Hyun Lee, Gabriel Ozorowski, Yuanzi Hua, Alba Torrents de la Peña, Steven W de Taeye, Travis Nieusma, Albert Cupo, Anila Yasmeen, Michael Golabek and 6 more

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.

0numbers the graph read from it
0cells of the map it votes in
101citing papers in PubMed
10.0field-weighted citation impact, top 1% 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

101 citing papers in PubMed, 122 citations in OpenAlex.

  1. Review
  2. Under the Radar: Immune Evasion, Pathogenesis and Control of HIV Infection.International journal of molecular sciences · 2025
    Review
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41 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

16 authors at 5 institutions in 3 countries.

Jean-Philippe JulienDepartment of Integrative Structural and Computational Biology, International AIDS Vaccine Initiative ( IAVI) Neutralizing Antibody Center, Collaboration for AIDS Vaccine Discovery, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037; Program in Molecular Structure and Function, The Hospital for Sick Children Research Institute, Toronto, ON, M5G 0A4, Canada; Departments of Biochemistry and Immunology, University of Toronto, Toronto, ON, M5S 1A8, Canada; wilson@scripps.edu jean-philippe.julien@sickkids.ca abward@scripps.edu.
Jeong Hyun LeeDepartment of Integrative Structural and Computational Biology, International AIDS Vaccine Initiative ( IAVI) Neutralizing Antibody Center, Collaboration for AIDS Vaccine Discovery, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037;
Gabriel OzorowskiDepartment of Integrative Structural and Computational Biology, International AIDS Vaccine Initiative ( IAVI) Neutralizing Antibody Center, Collaboration for AIDS Vaccine Discovery, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037;
Yuanzi HuaDepartment of Integrative Structural and Computational Biology, International AIDS Vaccine Initiative ( IAVI) Neutralizing Antibody Center, Collaboration for AIDS Vaccine Discovery, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037;
Alba Torrents de la PeñaDepartment of Medical Microbiology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands;
Steven W de TaeyeDepartment of Medical Microbiology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands;
Travis NieusmaDepartment of Integrative Structural and Computational Biology, International AIDS Vaccine Initiative ( IAVI) Neutralizing Antibody Center, Collaboration for AIDS Vaccine Discovery, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037;
Albert CupoDepartment of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021;
Anila YasmeenDepartment of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021;
Michael GolabekDepartment of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021;
Pavel PugachDepartment of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021;
P J KlasseDepartment of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021;
John P MooreDepartment of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021;
Rogier W SandersDepartment of Medical Microbiology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021;
Andrew B WardDepartment of Integrative Structural and Computational Biology, International AIDS Vaccine Initiative ( IAVI) Neutralizing Antibody Center, Collaboration for AIDS Vaccine Discovery, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037; wilson@scripps.edu jean-philippe.julien@sickkids.ca abward@scripps.edu.
Ian A WilsonDepartment of Integrative Structural and Computational Biology, International AIDS Vaccine Initiative ( IAVI) Neutralizing Antibody Center, Collaboration for AIDS Vaccine Discovery, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037; The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037 wilson@scripps.edu jean-philippe.julien@sickkids.ca abward@scripps.edu.
Cornell University · USScripps Research Institute · USInternational AIDS Vaccine Initiative · USUniversity of Amsterdam · NLAcademic Medical Center · 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 WILSON, IAN A · 2009 to 2014
$16.0M
NEUTRALIZATION OF PRIMARY HIV1 VIRUSESR37AI036082 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI MOORE, JOHN P · 1998 to 2017
$7.0M
Structural Biology of HIV-1 Neutralizing Antibody Targets for Vaccine DesignR01AI084817 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI WILSON, IAN A · 2009 to 2013
$3.2M
Structure and dynamics of native HIV-1 envelope trimersR56AI084817 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI WILSON, IAN A · 2015 to 2015
$593k
European Research Council 280829NIAID NIH HHS P01 AI082362NIAID NIH HHS P01 AI110657NIAID NIH HHS R01 AI084817NIAID NIH HHS R37 AI036082NIAID NIH HHS R37 AI36082NIAID NIH HHS R56 AI084817NIAID NIH HHS UM1 AI100663
6 · The paper itself

Abstract

A key challenge in the quest toward an HIV-1 vaccine is design of immunogens that can generate a broadly neutralizing antibody (bnAb) response against the enormous sequence diversity of the HIV-1 envelope glycoprotein (Env). We previously demonstrated that a recombinant, soluble, fully cleaved SOSIP.664 trimer based on the clade A BG505 sequence is a faithful antigenic and structural mimic of the native trimer in its prefusion conformation. Here, we sought clade C native-like trimers with comparable properties. We identified DU422 and ZM197M SOSIP.664 trimers as being appropriately thermostable (Tm of 63.4 °C and 62.7 °C, respectively) and predominantly native-like, as determined by negative-stain electron microscopy (EM). Size exclusion chromatography, ELISA, and surface plasmon resonance further showed that these trimers properly display epitopes for all of the major bnAb classes, including quaternary-dependent, trimer-apex (e.g., PGT145) and gp120/gp41 interface (e.g., PGT151) epitopes. A cryo-EM reconstruction of the ZM197M SOSIP.664 trimer complexed with VRC01 Fab against the CD4 binding site at subnanometer resolution revealed a striking overall similarity to its BG505 counterpart with expected local conformational differences in the gp120 V1, V2, and V4 loops. These stable clade C trimers contribute additional diversity to the pool of native-like Env immunogens as key components of strategies to induce bnAbs to HIV-1.

Indexed as

Drug DesignProtein MultimerizationCryoelectron Microscopyenv Gene Products, Human Immunodeficiency VirusHIV-1HIV AntigensHumansImmunoglobulin Fab FragmentsModels, MolecularNegative StainingProtein StabilitySolubilityTemperatureenv Gene Products, Human Immunodeficiency VirusHIV AntigensImmunoglobulin Fab Fragmentsantigenic diversityclade C trimersHIV-1 envelopeHIV immunogensneutralizing antibodies

Identifiers

PMID26372963
PMCPMC4586835
OpenAlexW1950875559

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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.