Enhancing and shaping the immunogenicity of native-like HIV-1 envelope trimers with a two-component protein nanoparticle.
Journal Article (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
- PMC6753213
Electronic International Standard Serial Number (EISSN)
- 2041-1723
Digital Object Identifier (DOI)
- 10.1038/s41467-019-12080-1
Language
- eng
Conference Location
- England