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

Published online

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Brouwer, PJM; Antanasijevic, A; Berndsen, Z; Yasmeen, A; Fiala, B; Bijl, TPL; Bontjer, I; Bale, JB; Sheffler, W; Allen, JD; Schorcht, A; Burger, JA; Camacho, M; Ellis, D; Cottrell, CA; Behrens, A-J; Catalano, M; Del Moral-Sánchez, I; Ketas, TJ; LaBranche, C; van Gils, MJ; Sliepen, K; Stewart, LJ; Crispin, M; Montefiori, DC; Baker, D; Moore, JP; Klasse, PJ; Ward, AB; King, NP; Sanders, RW

Published Date

  • September 19, 2019

Published In

Volume / Issue

  • 10 / 1

Start / End Page

  • 4272 -

PubMed ID

  • 31537780

Pubmed Central ID

  • 31537780

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-019-12080-1

Language

  • eng

Conference Location

  • England