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Structure and immunogenicity of a stabilized HIV-1 envelope trimer based on a group-M consensus sequence

Author

Listed:
  • Kwinten Sliepen

    (University of Amsterdam)

  • Byung Woo Han

    (Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute
    Seoul National University)

  • Ilja Bontjer

    (University of Amsterdam)

  • Petra Mooij

    (Biomedical Primate Research Centre)

  • Fernando Garces

    (Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute
    Amgen Research, Amgen Inc.)

  • Anna-Janina Behrens

    (University of Oxford
    New England Biolabs Inc.)

  • Kimmo Rantalainen

    (Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute)

  • Sonu Kumar

    (Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute)

  • Anita Sarkar

    (Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute)

  • Philip J. M. Brouwer

    (University of Amsterdam)

  • Yuanzi Hua

    (Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute)

  • Monica Tolazzi

    (IRCCS San Raffaele Scientific Institute)

  • Edith Schermer

    (University of Amsterdam)

  • Jonathan L. Torres

    (Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute)

  • Gabriel Ozorowski

    (Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute)

  • Patricia Woude

    (University of Amsterdam)

  • Alba Torrents Peña

    (University of Amsterdam)

  • Mariëlle J. Breemen

    (University of Amsterdam)

  • Juan Miguel Camacho-Sánchez

    (University of Amsterdam)

  • Judith A. Burger

    (University of Amsterdam)

  • Max Medina-Ramírez

    (University of Amsterdam)

  • Nuria González

    (Instituto de Salud Carlos III)

  • Jose Alcami

    (Instituto de Salud Carlos III)

  • Celia LaBranche

    (Duke University Medical Center)

  • Gabriella Scarlatti

    (IRCCS San Raffaele Scientific Institute)

  • Marit J. Gils

    (University of Amsterdam)

  • Max Crispin

    (University of Oxford
    University of Southampton)

  • David C. Montefiori

    (Duke University Medical Center)

  • Andrew B. Ward

    (Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute)

  • Gerrit Koopman

    (Biomedical Primate Research Centre)

  • John P. Moore

    (Weill Medical College of Cornell University)

  • Robin J. Shattock

    (Imperial College London)

  • Willy M. Bogers

    (Biomedical Primate Research Centre)

  • Ian A. Wilson

    (Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute
    The Scripps Research Institute)

  • Rogier W. Sanders

    (University of Amsterdam
    Weill Medical College of Cornell University)

Abstract

Stabilized HIV-1 envelope glycoproteins (Env) that resemble the native Env are utilized in vaccination strategies aimed at inducing broadly neutralizing antibodies (bNAbs). To limit the exposure of rare isolate-specific antigenic residues/determinants we generated a SOSIP trimer based on a consensus sequence of all HIV-1 group M isolates (ConM). The ConM trimer displays the epitopes of most known bNAbs and several germline bNAb precursors. The crystal structure of the ConM trimer at 3.9 Å resolution resembles that of the native Env trimer and its antigenic surface displays few rare residues. The ConM trimer elicits strong NAb responses against the autologous virus in rabbits and macaques that are significantly enhanced when it is presented on ferritin nanoparticles. The dominant NAb specificity is directed against an epitope at or close to the trimer apex. Immunogens based on consensus sequences might have utility in engineering vaccines against HIV-1 and other viruses.

Suggested Citation

  • Kwinten Sliepen & Byung Woo Han & Ilja Bontjer & Petra Mooij & Fernando Garces & Anna-Janina Behrens & Kimmo Rantalainen & Sonu Kumar & Anita Sarkar & Philip J. M. Brouwer & Yuanzi Hua & Monica Tolazz, 2019. "Structure and immunogenicity of a stabilized HIV-1 envelope trimer based on a group-M consensus sequence," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10262-5
    DOI: 10.1038/s41467-019-10262-5
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    Cited by:

    1. Mathieu Claireaux & Tom G. Caniels & Marlon Gast & Julianna Han & Denise Guerra & Gius Kerster & Barbera D. C. Schaik & Aldo Jongejan & Angela I. Schriek & Marloes Grobben & Philip J. M. Brouwer & Kar, 2022. "A public antibody class recognizes an S2 epitope exposed on open conformations of SARS-CoV-2 spike," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    2. Daniel Ellis & Julia Lederhofer & Oliver J. Acton & Yaroslav Tsybovsky & Sally Kephart & Christina Yap & Rebecca A. Gillespie & Adrian Creanga & Audrey Olshefsky & Tyler Stephens & Deleah Pettie & Mic, 2022. "Structure-based design of stabilized recombinant influenza neuraminidase tetramers," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    3. Jelle Schooten & Elinaz Farokhi & Anna Schorcht & Tom L. G. M. Kerkhof & Hongmei Gao & Patricia Woude & Judith A. Burger & Tim G. Rijkhold Meesters & Tom Bijl & Riham Ghalaiyini & Hannah L. Turner & J, 2022. "Identification of IOMA-class neutralizing antibodies targeting the CD4-binding site on the HIV-1 envelope glycoprotein," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    4. Yi-Nan Zhang & Jennifer Paynter & Aleksandar Antanasijevic & Joel D. Allen & Mor Eldad & Yi-Zong Lee & Jeffrey Copps & Maddy L. Newby & Linling He & Deborah Chavez & Pat Frost & Anna Goodroe & John Du, 2023. "Single-component multilayered self-assembling protein nanoparticles presenting glycan-trimmed uncleaved prefusion optimized envelope trimers as HIV-1 vaccine candidates," Nature Communications, Nature, vol. 14(1), pages 1-29, December.

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