High-Density Array of Well-Ordered HIV-1 Spikes on Synthetic Liposomal Nanoparticles Efficiently Activate B Cells.

TitleHigh-Density Array of Well-Ordered HIV-1 Spikes on Synthetic Liposomal Nanoparticles Efficiently Activate B Cells.
Publication TypeJournal Article
Year of Publication2016
AuthorsIngale J, Stano A, Guenaga J, Sharma SKumar, Nemazee D, Zwick MB, Wyatt RT
JournalCell Rep
Volume15
Issue9
Pagination1986-99
Date Published05/31/2016
ISSN2211-1247
Abstract

A major step toward an HIV-1 vaccine is an immunogen capable of inducing neutralizing antibodies. Envelope glycoprotein (Env) mimetics, such as the NFL and SOSIP designs, generate native-like, well-ordered trimers and elicit tier 2 homologous neutralization (SOSIPs). We reasoned that the display of well-ordered trimers by high-density, particulate array would increase B cell activation compared to soluble trimers. Here, we present the design of liposomal nanoparticles displaying well-ordered Env spike trimers on their surface. Biophysical analysis, cryo- and negative stain electron microscopy, as well as binding analysis with a panel of broadly neutralizing antibodies confirm a high-density, well-ordered trimer particulate array. The Env-trimer-conjugated liposomes were superior to soluble trimers in activating B cells ex vivo and germinal center B cells in vivo. In addition, the trimer-conjugated liposomes elicited modest tier 2 homologous neutralizing antibodies. The trimer-conjugated liposomes represent a promising initial lead toward the development of more effective HIV vaccine immunogens.

DOI10.1016/j.celrep.2016.04.078
Alternate JournalCell Rep
PubMed ID27210756
PubMed Central IDPMC4889521
Grant ListP01 AI104722 / AI / NIAID NIH HHS / United States
R01 AI073148 / AI / NIAID NIH HHS / United States
R01 AI098602 / AI / NIAID NIH HHS / United States
UM1 AI100663 / AI / NIAID NIH HHS / United States
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