期刊
NATURE COMMUNICATIONS
卷 7, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms12041
关键词
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资金
- International AIDS Vaccine Initiative Neutralizing Antibody Center
- CAVD
- Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery [CHAVI-ID UM1 AI00663]
- HIV Vaccine Research and Design (HIVRAD) programme [P01 AI110657]
- Joint Center of Structural Genomics (JCSG) - NIH NIGMS, Protein Structure Initiative [U54 GM094586, AI073148, AI084817]
Structures of BG505 SOSIP. 664 trimer in complex with broadly neutralizing antibodies (bNAbs) have revealed the critical role of trimeric context for immune recognition of HIV-1. Presentation of trimeric HIV-1 antigens on nanoparticles may thus provide promising vaccine candidates. Here we report the rational design, structural analysis and antigenic evaluation of HIV-1 trimer-presenting nanoparticles. We first demonstrate that both V1V2 and gp120 can be presented in native-like trimeric conformations on nanoparticles. We then design nanoparticles presenting various forms of stabilized gp140 trimer based on ferritin and a large, 60-meric E2p that displays 20 spikes mimicking virus-like particles (VLPs). Particle assembly is confirmed by electron microscopy (EM), while antigenic profiles are generated using representative bNAbs and non-NAbs. Lastly, we demonstrate high-yield gp140 nanoparticle production and robust stimulation of B cells carrying cognate VRC01 receptors by gp120 and gp140 nanoparticles. Together, our study provides an arsenal of multivalent immunogens for HIV-1 vaccine development.
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