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

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, Judith A. Burger, Miguel Camacho, Daniel Ellis, Christopher A. Cottrell, Anna-Janina Behrens, Marco Catalano, Iván del Moral-Sánchez, Thomas J. Ketas, Celia LaBranche, Marit J. van Gils, Kwinten Sliepen, Lance J. Stewart, Max Crispin, David C. Montefiori, David Baker, John P. Moore, Per Johan Klasse, Andrew B. Ward, Neil P. King () and Rogier W. Sanders ()
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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
Tom P. L. Bijl: University of Amsterdam
Ilja Bontjer: University of Amsterdam
Jacob B. Bale: University of Washington
William Sheffler: 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
Christopher A. Cottrell: The Scripps Research Institute
Anna-Janina Behrens: University of Oxford
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
Max Crispin: University of Southampton
David C. Montefiori: Duke University Medical Center
David Baker: 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
Rogier W. Sanders: University of Amsterdam

Nature Communications, 2019, vol. 10, issue 1, 1-17

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-12080-1

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