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Enhancing and shaping the immunogenicity of native-like HIV-1 envelope trimers with a two-component protein nanoparticle

Author

Listed:
  • Philip J. M. Brouwer

    (University of Amsterdam)

  • Aleksandar Antanasijevic

    (The Scripps Research Institute)

  • Zachary Berndsen

    (The Scripps Research Institute)

  • Anila Yasmeen

    (Weill Medical College of Cornell University)

  • Brooke Fiala

    (University of Washington
    University of Washington)

  • Tom P. L. Bijl

    (University of Amsterdam)

  • Ilja Bontjer

    (University of Amsterdam)

  • Jacob B. Bale

    (University of Washington
    University of Washington
    Arzeda Corporation)

  • William Sheffler

    (University of Washington
    University of Washington)

  • Joel D. Allen

    (University of Southampton)

  • Anna Schorcht

    (University of Amsterdam)

  • Judith A. Burger

    (University of Amsterdam)

  • Miguel Camacho

    (University of Amsterdam)

  • Daniel Ellis

    (University of Washington
    University of Washington)

  • Christopher A. Cottrell

    (The Scripps Research Institute)

  • Anna-Janina Behrens

    (University of Oxford
    New England Biolabs, Inc.)

  • Marco Catalano

    (University of Amsterdam)

  • Iván del Moral-Sánchez

    (University of Amsterdam)

  • Thomas J. Ketas

    (Weill Medical College of Cornell University)

  • Celia LaBranche

    (Duke University Medical Center)

  • Marit J. van Gils

    (University of Amsterdam)

  • Kwinten Sliepen

    (University of Amsterdam)

  • Lance J. Stewart

    (University of Washington
    University of Washington)

  • Max Crispin

    (University of Southampton
    University of Oxford)

  • David C. Montefiori

    (Duke University Medical Center)

  • David Baker

    (University of Washington
    University of Washington
    University of Washington)

  • John P. Moore

    (Weill Medical College of Cornell University)

  • Per Johan Klasse

    (Weill Medical College of Cornell University)

  • Andrew B. Ward

    (The Scripps Research Institute)

  • Neil P. King

    (University of Washington
    University of Washington)

  • Rogier W. Sanders

    (University of Amsterdam)

Abstract

The development of native-like HIV-1 envelope (Env) trimer antigens has enabled the induction of neutralizing antibody (NAb) responses against neutralization-resistant HIV-1 strains in animal models. However, NAb responses are relatively weak and narrow in specificity. Displaying antigens in a multivalent fashion on nanoparticles (NPs) is an established strategy to increase their immunogenicity. Here we present the design and characterization of two-component protein NPs displaying 20 stabilized SOSIP trimers from various HIV-1 strains. The two-component nature permits the incorporation of exclusively well-folded, native-like Env trimers into NPs that self-assemble in vitro with high efficiency. Immunization studies show that the NPs are particularly efficacious as priming immunogens, improve the quality of the Ab response over a conventional one-component nanoparticle system, and are most effective when SOSIP trimers with an apex-proximate neutralizing epitope are displayed. Their ability to enhance and shape the immunogenicity of SOSIP trimers make these NPs a promising immunogen platform.

Suggested Citation

  • Philip J. M. Brouwer & Aleksandar Antanasijevic & Zachary Berndsen & Anila Yasmeen & Brooke Fiala & Tom P. L. Bijl & Ilja Bontjer & Jacob B. Bale & William Sheffler & Joel D. Allen & Anna Schorcht & J, 2019. "Enhancing and shaping the immunogenicity of native-like HIV-1 envelope trimers with a two-component protein nanoparticle," Nature Communications, Nature, vol. 10(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12080-1
    DOI: 10.1038/s41467-019-12080-1
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