Presenting native-like trimeric HIV-1 antigens with self-assembling nanoparticles.

TitlePresenting native-like trimeric HIV-1 antigens with self-assembling nanoparticles.
Publication TypeJournal Article
Year of Publication2016
AuthorsHe L, de Val N, Morris CD, Vora N, Thinnes TC, Kong L, Azadnia P, Sok D, Zhou B, Burton DR, Wilson IA, Nemazee D, Ward AB, Zhu J
JournalNat Commun
Volume7
Pagination12041
Date Published06/28/2016
ISSN2041-1723
Abstract

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.

DOI10.1038/ncomms12041
Alternate JournalNat Commun
PubMed ID27349934
Grant ListP01 AI110657 / AI / NIAID NIH HHS / United States
R01 AI084817 / AI / NIAID NIH HHS / United States
U54 GM094586 / GM / NIGMS NIH HHS / United States
UM1 AI100663 / AI / NIAID NIH HHS / United States
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