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ScholarsBetaWeill Cornell Medicine

Overview

TRIMERIC HIV-1 ENVELOPE GLYCOPROTEIN IMMUNOGENS
We use our accumulated knowledge of the structure and function of the HIV-1 envelope (Env) glycoprotein trimer to design and evaluate recombinant forms of these proteins as immunogens for vaccine development. In the initial stages of the virus replication cycle, the envelope glycoproteins attach HIV-1 to its susceptible target cells, which are predominantly CD4-positive T-cells, macrophages and dendritic cells. The Env trimer then undergoes a series of receptor-mediated conformational changes that enable the virus and cell membranes to fuse, and the virus to infect the cell. The Env glycoproteins are also critical targets for host immunity, particularly virus neutralizing antibodies (NAbs). These antibodies bind to functional Env glycoproteins on the virus surface and block their activity. Inducing broadly active NAbs by immunization with Env glycoproteins would, therefore, be a valuable component of a vaccine to prevent HIV-1 infection. To this end, we have designed and are developing stable, recombinant trimers that faithfully mimic the native, functional trimers that are present on the virus surface. These trimers, called SOSIP glycoproteins, induce narrow-specificity NAbs in test animals, and we are working to broaden these responses. All of this work is carried out as part of a multi-disciplinary team with colleagues in other institutions, including structural biologists and immunologists.

Highlights

  1. 1
    JAMA · 2021
    JPJohn P Moore
    PMID: 33507218DOIFirst author177 citations
  2. 2
    Pathogens & immunity · 2021
    EGEncouse GoldenZZZhen ZhaoMCMelissa CushingRWRogier W Sanders+2 more →JPJohn P Moore
    PMID: 34136730PMCID: PMC8201795DOISenior author97 citations
  3. 3
    Journal of virology · 2020
    RWRogier W SandersPKP.J. KlasseACAlbert CupoJPJohn P Moore
    PMID: 31852794PMCID: PMC7158715DOISenior author29 citations

Publications

458 publications

Funding

26 grantsView NIH portfolio on RePORTER ↗

Active

8 grants
  • PI
    Targeting germline-bNAbs via SOSIP trimers;
    National Institute of Allergy and Infectious Diseases · 2026–2031
    P01AI197052-01
  • Co-I
    An early life multivalent immunization strategy for induction of neutralization breadth
    National Institute of Allergy and Infectious Diseases · 2025–2030
    U01AI192448-02
  • Co-I
    Translating germline-targeting HIV Env SOSIP immunization of infants: targeting bnAbs in early life
    National Institute of Allergy and Infectious Diseases · 2025–2030
    P01AI189362-02
  • PI
    Neutralization of primary HIV-1 viruses
    National Institute of Allergy and Infectious Diseases · 2018–2028· 2 renewals
    R01AI036082-34
  • Sub-PI
    INV63951 - Trimer based germline-targeting immunization to induce HIV-1 bNAbs - AUMC
    Bill & Melinda Gates Foundation · 2025–2026 · via Amsterdam University Medical Centers
    INV-063951
  • PI
    Cleaved, stabilized HIV-1 Env trimers for structural and vaccine studies
    National Institute of Allergy and Infectious Diseases · 2015–2026· 3 renewals
    P01AI110657-10 CORE A
  • PI
    INV091003 Targeting germline-bNAbs via SOSIP trimers
    Bill & Melinda Gates Foundation · 2025–2026
    BMGF INV-091003
  • Sub-PI
    Phase 1 study of BG505 SOSIP Trimer boosting in GT1.1 primed individuals
    Bill & Melinda Gates Foundation · 2023–2025 · via Rockefeller University
    INV-048573
Completed grants (18)
  • Sub-PI
    Phase 1 clinical study testing GT1.1 trimer
    Bill & Melinda Gates Foundation · 2019–2024 · via Rockefeller University
    INV-008818
  • Sub-PI
    Design HIV Trimer Immunogens to Elicit bNAbs Aimed at two Epitopes
    Bill & Melinda Gates Foundation · 2019–2023 · via Amsterdam University Medical Centers
    INV-002022
  • PI
    Next Generation BG505 SOSIP.664-trimer Based HIV Vaccines
    Bill & Melinda Gates Foundation · 2016–2020
    OPP1132237-03
  • PI
    HIV-1 Monoclonal Antibodies
    University of Maryland, Baltimore · 2019–2020
    UMB 194671-01
  • Sub-PI
    Structure Based Immunogen Design at UW-IPD
    Bill & Melinda Gates Foundation · 2018–2020 · via University of Washington, The
    OPP1156262
  • Sub-PI
    Development of Nearest Neighbor Immunogens for HIV-1 Vaccines
    Bill & Melinda Gates Foundation · 2014–2019 · via University of Washington, The
    OPP1111923
  • PI
    Neutralization of Primary HIV-1 Viruses
    National Institute of Allergy and Infectious Diseases · 2008–2018· 2 renewals
    R37AI036082-25
  • Sub-PI
    Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery
    National Institute of Allergy and Infectious Diseases · 2013–2016 · via Scripps Research Institute
    UM1AI100663-04
  • PI
    Second Receptors for Primate Immunodeficiency Viruses
    National Institute of Allergy and Infectious Diseases · 2011–2016
    R01AI041420-20
  • PI
    Trimer Production and Immunogenicity Testing
    NIAID · 2009–2015 · via NIH RePORTER
    P01AI082362-06S1
  • PI
    A practical microbicide based on HIV-1 entry inhibitors
    NIAID · 2008–2013 · via NIH RePORTER
    U19AI076982-04S1
  • PI
    Modified envelope glycoproteins for HIV-1 vaccine
    NIAID · 1999–2011 · via NIH RePORTER
    R01AI045463-13
  • PI
    CORE--INHIBITOR ACQUISITION, EVALUATION AND FORMULATION
    NIAID · 2005–2009 · via NIH RePORTER
    U19AI065413-03
  • MPI
    STRATEGIES OF IMMUNE EVASION IN AIDS
    NCRR · 2008–2009 · via NIH RePORTER
    P51RR000168-47
  • PI
    Viral Host And Combinational Influences on PRO 140
    NIAID · 2006–2009 · via NIH RePORTER
    U19AI066329-04
  • PI
    ENTRY INHIBITORS AS TOPICAL MICROBICIDES AGAINST HIV-1
    NIAID · 2001–2005 · via NIH RePORTER
    P01AI052048-04
  • PI
    CHRYSTALLIZING DISULFIDE-STABILIZED HIV-1 ENV PROTEINS
    NIAID · 2003–2005 · via NIH RePORTER
    R21AI054159-02
  • PI
    HIV NEUTRALIZATION IN VITRO & IN SHIV-INFECTED MACAQUES
    NHLBI · 1997–2002 · via NIH RePORTER
    R01HL059735-06

News mentions

3 mentionsView all WCM news ↗
  • NIH Grant Aims for Childhood Vaccine Against HIV
    September 18, 2025

    A multi-institutional team led by Weill Cornell Medicine investigators has been awarded a five-year, $20.8 million grant from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, for advanced preclinical development of a promising experimental HIV vaccine.

  • The Quest for an HIV Vaccine
    August 20, 2025

    Along with an international team, Dr. John Moore, has brought biomedicine closer than ever to an HIV vaccine.

  • Childhood HIV Vaccination Strategy Shows Promise in Study
    August 30, 2024

    Research at Weill Cornell Medicine suggests that childhood immunization against HIV could one day provide protection before risk of contracting this potentially fatal infection dramatically increases in adolescence.

Media highlights

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Mentoring

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