ArticleNature structural & molecular biology2015
Crystal structure, conformational fixation and entry-related interactions of mature ligand-free HIV-1 Env.
Registry-linked trialOpen access · greenAbstract read
In one paragraph
Article in Nature structural & molecular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03783130 (VRC 018), which is not on this map. Cited by 287 papers.
0numbers the graph read from it
0cells of the map it votes in
287citing papers in PubMed
24.3field-weighted citation impact, top 1% of its field
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.
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.
VRC 018: A Phase I Dose Escalation, Randomized, Open-Label Clinical Trial to Evaluate Dose, Safety, Tolerability and Immunogenicity of a HIV-1 Vaccine, VRC-HIVRGP096-00-VP, With Alum in Healthy Adults
Who cites it
287 citing papers in PubMed, 364 citations in OpenAlex.
- Use of 3M-052-AF with Alum adjuvant in HIV trimer vaccine induces human autologous neutralizing antibodies.The Journal of experimental medicine · 2024Trial
- RNA-encoded PGT121-LS anti-HIV antibody: Comprehensive preclinical characterization and translational pharmacokinetics.Molecular therapy. Nucleic acids · 2026Article
- Article
- Structural determination of the HIV-1 Variable Region 3 epitope of antibody 19b.Journal of virology · 2026Article
- Canonical Antibodies Adopt Distinct Binding Modes to Recognize Viral Glycan Shields.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Recent advances in HIV-1 envelope-based vaccine designs for guiding broadly neutralizing antibody response.Journal of virology · 2026Review
- Identification of a potent V3 glycan site broadly neutralizing antibody targeting an N332Nature immunology · 2026Article
- Conformational landscape of HIV-1 Env from closed to fully open.Nature communications · 2026Article
- Host Glycan-Lectin Interplay in SARS-CoV-2 Infection.International journal of molecular sciences · 2026Review
- A Mammalian Surface Display Platform to Optimize the Antigenicity of Viral Proteins for Vaccine Design.bioRxiv : the preprint server for biology · 2026Article
- Structure of HIV-1 Env glycoprotein on virions reveals an alternative fusion subunit organization and native membrane coupling.bioRxiv : the preprint server for biology · 2026Article
- Novel HIV-1 fusion peptide immunogens using glycan-engineered alphavirus-like particles.NPJ vaccines · 2025Article
- The HIV-1 envelope glycoprotein: structure, function and interactions with neutralizing antibodies.Nature reviews. Microbiology · 2025Review
- Structural and genetic basis of HIV-1 envelope V2 apex recognition by rhesus broadly neutralizing antibodies.The Journal of experimental medicine · 2025Article
- Identification of a broad and potent V3 glycan site bNAb targeting an N332bioRxiv : the preprint server for biology · 2025Article
- Accelerated cGMP production of near-native HIV-1 Env trimers following electroporation transfection and immunogenicity analysis.NPJ vaccines · 2025Article
- Transient glycan shield reduction induces CD4-binding site broadly neutralizing antibodies in SHIV-infected macaques.Cell reports · 2025Article
- Article
- Multiple Mechanisms of HIV-1 Resistance to PGT135 in a Chinese Subtype B' Slow Progressor.Pathogens (Basel, Switzerland) · 2025Article
- Antigen persistence and TLR stimulation contribute to induction of a durable HIV-1-specific neutralizing antibody response.Nature communications · 2025Article
227 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
53 authors at 15 institutions in 2 countries.
Young Do KwonVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Marie PanceraVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Priyamvada AcharyaVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Ivelin S GeorgievVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Emma T CrooksSan Diego Biomedical Research Institute, San Diego, California, USA.
Jason GormanVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
M Gordon JoyceVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Miklos GuttmanDepartment of Medicinal Chemistry, University of Washington, Seattle, Washington, USA.
Xiaochu MaDepartment of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut, USA.
Sandeep NarpalaVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Cinque SotoVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Daniel S TerryDepartment of Physiology and Biophysics, Weill Cornell Medical College of Cornell University, New York, New York, USA.
Yongping YangVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Tongqing ZhouVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.ORCID 0000000239354637
Goran Ahlsen1] Department of Biochemistry &Molecular Biophysics, Columbia University, New York, New York, USA. [2] Department of Systems Biology, Columbia University, New York, New York, USA.
Robert T BailerVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Michael ChambersVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Gwo-Yu ChuangVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Nicole A Doria-RoseVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Aliaksandr DruzVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Mark A Hallen1] Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. [2] Department of Biochemistry, Duke University Medical Center, Durham, North Carolina, USA.
Adam HarnedElectron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
Tatsiana KirysVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Mark K LouderVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Sijy O'DellVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Gilad OfekVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Keiko OsawaSan Diego Biomedical Research Institute, San Diego, California, USA.
Madhu PrabhakaranVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Mallika SastryVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Guillaume B E Stewart-JonesVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Jonathan StuckeyVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Paul V ThomasVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Tishina TittleyVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Constance WilliamsNew York University School of Medicine, New York, New York, USA.
Baoshan ZhangVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Hong ZhaoDepartment of Physiology and Biophysics, Weill Cornell Medical College of Cornell University, New York, New York, USA.
Zhou ZhouDepartment of Physiology and Biophysics, Weill Cornell Medical College of Cornell University, New York, New York, USA.
Bruce R Donald1] Department of Biochemistry, Duke University Medical Center, Durham, North Carolina, USA. [2] Department of Chemistry, Duke University, Durham, North Carolina, USA. [3] Department of Computer Science, Duke University, Durham, North Carolina, USA.
Lawrence K LeeStructural and Computational Biology Division, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia.
Susan Zolla-Pazner1] New York University School of Medicine, New York, New York, USA. [2] New York Veterans Affairs Harbor Healthcare System, New York, New York, USA.
Ulrich BaxaElectron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
Arne SchönDepartment of Biology, Johns Hopkins University, Baltimore, Maryland, USA.
Ernesto FreireDepartment of Biology, Johns Hopkins University, Baltimore, Maryland, USA.
Lawrence Shapiro1] Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. [2] Department of Biochemistry &Molecular Biophysics, Columbia University, New York, New York, USA.
Kelly K LeeDepartment of Medicinal Chemistry, University of Washington, Seattle, Washington, USA.
James ArthosLaboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
James B Munro1] Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut, USA. [2] Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, USA.
Scott C BlanchardDepartment of Physiology and Biophysics, Weill Cornell Medical College of Cornell University, New York, New York, USA.
Walther MothesDepartment of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut, USA.
James M BinleySan Diego Biomedical Research Institute, San Diego, California, USA.
Adrian B McDermottVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
John R MascolaVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Peter D KwongVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
National Institutes of Health · USCornell University · USSan Diego Biomedical Research Institute · USJohns Hopkins University · USLeidos (United States) · USUniversity of Washington · USYale University · USColumbia University · USDuke Medical Center · USDuke University · USNational Institute of Allergy and Infectious Diseases · USNew York University · USTufts University · USVA NY Harbor Healthcare System · USVictor Chang Cardiac Research Institute · AU
Funding
Understanding Envelope Function in HIV-1 Infection: The Design, Synthesis and Validation of Small Molecule HIV-1 Env InhibitorsP01GM056550 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI ABRAMS, CAMERON F · 1997 to 2018
$31.2MDesign Of ImmunogensZIAAI005024 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI ZHOU, TONGQING · 2009 to 2025
$21.5MMechanisms Of Humoral EvasionZIAAI005023 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI ZHOU, TONGQING · 2009 to 2025
$18.6MVaccines to Induce Functional Antibodies Targeting the V2 Loop P01AI100151 · NIAID · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI WANG, SHIXIA · 2012 to 2017
$15.4MNon-Human PrimatesP01AI104722 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI WYATT, RICHARD THOMAS · 2014 to 2018
$14.6MInteraction of HIV envelope with cell surface receptorsZIAAI000883 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI ARTHOS, JAMES L · 2009 to 2024
$14.0MPure and Authentic HIV-1 Env ImmunogensR01AI093278 · NIAID · TORREY PINES INST FOR MOLECULAR STUDIES · PI BINLEY, JAMES M · 2011 to 2024
$11.6MPROTECTIVE HUMAN MONOCLONAL ANTIBODIES TO HIV1R01HL059725 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ZOLLA-PAZNER, SUSAN B · 1997 to 2014
$8.8MDesign of Antigenically-Specific Probes for Sera Analysis and MAb IsolationZICAI005111 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI ZHOU, TONGQING · 2010 to 2025
$4.3MRational Immunogen Design Using Computational MethodsZICAI005114 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI RAWI, REDA · 2010 to 2025
$4.3MComputational Structure-Based Protein DesignR01GM078031 · NIGMS · DUKE UNIVERSITY · PI DONALD, BRUCE R. · 2008 to 2021
$4.3MComputational Tools for Structural AnalysisZICAI005112 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI RAWI, REDA · 2010 to 2025
$4.1MCCR NIH HHS HHSN261200800001CIntramural NIH HHS ZIA AI005024NCI NIH HHS HHSN261200800001ENHLBI NIH HHS P01-HL59725NHLBI NIH HHS R01 HL059725NIAID NIH HHS P01 AI100151NIAID NIH HHS P01-AI100151NIAID NIH HHS P01 AI104722NIAID NIH HHS P01-AI104722NIAID NIH HHS R01 AI093278NIAID NIH HHS R01 AI100790NIAID NIH HHS R01-AI93278NIAID NIH HHS R21 AI100696NIAID NIH HHS R21-AI100696NIAID NIH HHS R21 AI112389NIAID NIH HHS R21-AI112389NIAID NIH HHS R33 AI084714NIAID NIH HHS R33-AI84714NIGMS NIH HHS P01 GM056550NIGMS NIH HHS P01-GM56550NIGMS NIH HHS R01 GM078031NIGMS NIH HHS R01 GM098859NIGMS NIH HHS R01-GM78031NIGMS NIH HHS R01-GM98859PHS HHS HHSN261200800001E.
Abstract
As the sole viral antigen on the HIV-1-virion surface, trimeric Env is a focus of vaccine efforts. Here we present the structure of the ligand-free HIV-1-Env trimer, fix its conformation and determine its receptor interactions. Epitope analyses revealed trimeric ligand-free Env to be structurally compatible with broadly neutralizing antibodies but not poorly neutralizing ones. We coupled these compatibility considerations with binding antigenicity to engineer conformationally fixed Envs, including a 201C 433C (DS) variant specifically recognized by broadly neutralizing antibodies. DS-Env retained nanomolar affinity for the CD4 receptor, with which it formed an asymmetric intermediate: a closed trimer bound by a single CD4 without the typical antigenic hallmarks of CD4 induction. Antigenicity-guided structural design can thus be used both to delineate mechanism and to fix conformation, with DS-Env trimers in virus-like-particle and soluble formats providing a new generation of vaccine antigens.
Indexed as
Antibodies, NeutralizingCD4 AntigensCrystallography, X-Rayenv Gene Products, Human Immunodeficiency VirusEpitopesHEK293 CellsHIV-1HIV AntibodiesHIV InfectionsHumansModels, MolecularProtein ConformationProtein MultimerizationVirus InternalizationAntibodies, NeutralizingCD4 Antigensenv Gene Products, Human Immunodeficiency VirusEpitopesHIV Antibodies
Identifiers
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Read underepoch 390
Registered trials
NCT03783130ClinicalTrials.gov
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.