ArticleImmunity2016
HIV Vaccine Design to Target Germline Precursors of Glycan-Dependent Broadly Neutralizing Antibodies.
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Article in Immunity, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 314 papers.
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314citing papers in PubMed
26.6field-weighted citation impact, top 1% of its field
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Who cites it
314 citing papers in PubMed, 435 citations in OpenAlex.
- Trial
- Vaccination with mRNA-encoded nanoparticles drives early maturation of HIV bnAb precursors in humans.Science (New York, N.Y.) · 2025Trial
- High Frequency of Chronic Urticaria Following an Investigational HIV-1 BG505 MD39.3 Trimer mRNA Vaccine in a Phase 1, Randomized, Open-Label Clinical Trial (HVTN 302).Annals of internal medicine · 2025Trial
- Vaccination induces HIV broadly neutralizing antibody precursors in humans.Science (New York, N.Y.) · 2022Trial
- Safety and antiviral activity of triple combination broadly neutralizing monoclonal antibody therapy against HIV-1: a phase 1 clinical trial.Nature medicine · 2022Trial
- Deletions in variable region 1 of the HIV envelope accelerate V3-glycan bNAb induction in SHIV-infected rhesus macaques.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Article
- Structural basis of diverse antibody recognition of conserved coronavirus spike S2 epitopes that contribute to protective immunity.bioRxiv : the preprint server for biology · 2026Article
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- Article
- Biophysical properties of IgD determine thresholds for self-tolerance and selection into germinal centers.bioRxiv : the preprint server for biology · 2026Article
- Rapid boosting increases germinal center responses to sequential vaccines.Nature immunology · 2026Article
- Induction of broadly neutralizing HIV antibodies by a two-step mechanism informs vaccine design.Science (New York, N.Y.) · 2026Article
- mRNA delivery of a class 1/4 SARS-CoV-2 neutralizing antibody protects against diverse sarbecoviruses in a lethal mouse challenge model.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Recent advances in HIV-1 envelope-based vaccine designs for guiding broadly neutralizing antibody response.Journal of virology · 2026Review
- Deep mining of the human antibody repertoire identifies frequent and genetically diverse CDRH3 topologies targetable by vaccination.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Germline-targeting HIV immunogen induces cross-neutralizing antibodies in outbred macaques.Immunity · 2026Article
- Decoding the glycan shield: Immune recognition and response to the HIV-1 envelope trimer.The Journal of biological chemistry · 2026Review
- Germline-somatic residue synergy reshapes antibody encounter-state pathways to enhance HIV-1 recognition.bioRxiv : the preprint server for biology · 2026Article
- Decoding epitope immunodominance in HIV Env using cryoEM and machine learning.bioRxiv : the preprint server for biology · 2026Article
254 more citing papers are in PubMed but not listed here.
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Authors and funding
29 authors at 5 institutions in 1 country.
Jon M SteichenDepartment of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
Daniel W KulpDepartment of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
Talar TokatlianKoch Institute for Integrative Cancer Research, MIT, Cambridge, MA 02139, USA.
Amelia EscolanoLaboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
Pia DosenovicLaboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
Robyn L StanfieldIAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, USA.
Laura E McCoyDepartment of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
Gabriel OzorowskiIAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, USA.
Xiaozhen HuDepartment of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
Oleksandr KalyuzhniyDepartment of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
Bryan BrineyDepartment of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
Torben SchiffnerDepartment of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
Fernando GarcesIAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, USA.
Natalia T FreundLaboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
Alexander D GitlinLaboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
Sergey MenisDepartment of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
Erik GeorgesonDepartment of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
Michael KubitzDepartment of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
Yumiko AdachiDepartment of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
Meaghan JonesDepartment of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
Andrew A MutafyanKoch Institute for Integrative Cancer Research, MIT, Cambridge, MA 02139, USA.
Dong Soo YunKoch Institute for Integrative Cancer Research, MIT, Cambridge, MA 02139, USA.
Christian T MayerLaboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
Andrew B WardIAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, USA.
Dennis R BurtonDepartment of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA; The Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139, USA.
Ian A WilsonIAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, USA; Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Darrell J IrvineKoch Institute for Integrative Cancer Research, MIT, Cambridge, MA 02139, USA; The Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; Departments of Biological Engineering and Materials Science & Engineering, MIT, Cambridge, MA 02139, USA.
Michel C NussenzweigLaboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address: nussen@mail.rockefeller.edu.
William R SchiefDepartment of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA; The Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139, USA. Electronic address: schief@scripps.edu.
International AIDS Vaccine Initiative · USScripps Research Institute · USRockefeller University · USKoch Institute for Integrative Cancer Research At MITRagon Institute of MGH, MIT and Harvard · US
Funding
Support Component D/Vaccine Discovery, Concept to ClinicUM1AI100663 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI BAROUCH, DAN H. · 2012 to 2018
$131.5MWeill Cornell/Rockefeller/Sloan-Kettering MST ProgramT32GM007739 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI HSU, KATHARINE C · 1985 to 2023
$51.1MStuctural basis of bNab activityP01AI100148 · NIAID · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI Pamela J Bjorkman · 2013 to 2026
$43.3MStructural studies of native-like SOSIP trimersP01AI110657 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI MOORE, JOHN P · 2015 to 2024
$35.4MX-ray Absorption Spectroscopy (XAS) pp.711-759P41GM103393 · NIGMS · STANFORD UNIVERSITY · PI HODGSON, KEITH O · 2012 to 2019
$30.6MPATHOGENESIS AND IMMUNOLOGY OF DISEASET32AI007244 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI NEMAZEE, DAVID · 1985 to 2022
$8.8MGlycan dependent epitopes of HIV broadly neutralizing antibodiesR01AI113867 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI PAULSON, JAMES C, SCHIEF, WILLIAM R. · 2014 to 2018
$4.8MStructural Biology of HIV-1 Neutralizing Antibody Targets for Vaccine DesignR01AI084817 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI WILSON, IAN A · 2009 to 2013
$3.2MStructure and dynamics of native HIV-1 envelope trimersR56AI084817 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI WILSON, IAN A · 2015 to 2015
$593kHoward Hughes Medical InstituteNIAID NIH HHS P01 AI100148NIAID NIH HHS P01 AI110657NIAID NIH HHS R01 AI084817NIAID NIH HHS R01 AI113867NIAID NIH HHS R56 AI084817NIAID NIH HHS T32 AI007244NIAID NIH HHS UM1 AI100663NIGMS NIH HHS P41 GM103393NIGMS NIH HHS T32 GM007739
Abstract
Broadly neutralizing antibodies (bnAbs) against the N332 supersite of the HIV envelope (Env) trimer are the most common bnAbs induced during infection, making them promising leads for vaccine design. Wild-type Env glycoproteins lack detectable affinity for supersite-bnAb germline precursors and are therefore unsuitable immunogens to prime supersite-bnAb responses. We employed mammalian cell surface display to design stabilized Env trimers with affinity for germline-reverted precursors of PGT121-class supersite bnAbs. The trimers maintained native-like antigenicity and structure, activated PGT121 inferred-germline B cells ex vivo when multimerized on liposomes, and primed PGT121-like responses in PGT121 inferred-germline knockin mice. Design intermediates have levels of epitope modification between wild-type and germline-targeting trimers; their mutation gradient suggests sequential immunization to induce bnAbs, in which the germline-targeting prime is followed by progressively less-mutated design intermediates and, lastly, with native trimers. The vaccine design strategies described could be utilized to target other epitopes on HIV or other pathogens.
Indexed as
AIDS VaccinesAmino Acid SequenceAnimalsAntibodies, NeutralizingB-Lymphocytesenv Gene Products, Human Immunodeficiency VirusEpitopesHIV-1HIV AntibodiesHIV InfectionsImmunizationMiceMice, KnockoutMutationPolysaccharidesSequence AlignmentAIDS VaccinesAntibodies, Neutralizingenv Gene Products, Human Immunodeficiency VirusEpitopesHIV AntibodiesPolysaccharides
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