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 LaBrancheMarit 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, Rogier W. Sanders

Research output: Contribution to journalArticleAcademicpeer-review

120 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)4272
JournalNature communications
Volume10
Issue number1
DOIs
Publication statusPublished - 2019

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