Prevention of cell death by antibodies selected from intracellular combinatorial libraries

Year
2016
Type(s)
Authors
He, L. de Val, N. Morris, C. D. Vora, N. Thinnes, T. C. Kong, L. Azadnia, P. Sok, Devin Zhou, Bin Burton, Dennis Wilson, Ian Nemazee, David Ward, Andrew Zhu, Jiang
Source
Nature Communications 2016
Url
http://dx.doi.org/10.1038/ncomms12041

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.

 

Technology Platform

Next-Generation Sequencing

Research Topics

Antibody Discovery