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- Title
Enhancing and shaping the immunogenicity of native-like HIV-1 envelope trimers with a two-component protein nanoparticle.
- Authors
Brouwer, Philip J. M.; Antanasijevic, Aleksandar; Berndsen, Zachary; Yasmeen, Anila; Fiala, Brooke; Bijl, Tom P. L.; Bontjer, Ilja; Bale, Jacob B.; Sheffler, William; Allen, Joel D.; Schorcht, Anna; Burger, Judith A.; Camacho, Miguel; Ellis, Daniel; Cottrell, Christopher A.; Behrens, Anna-Janina; Catalano, Marco; del Moral-Sánchez, Iván; Ketas, Thomas J.; LaBranche, Celia
- 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. Nanoparticles are a promising approach to increase immunogenicity of protein antigens for vaccines. Here, Brouwer et al. design self-assembling, two-component protein NPs that present native-like SOSIP trimers of HIV envelope protein and determine immunogenicity in a small animal model.
- Subjects
BACTERIAL vaccines; PROTEINS; ANIMAL models in research; ANTIGENS
- Publication
Nature Communications, 2019, Vol 10, Issue 1, pN.PAG
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-019-12080-1