Presenting native-like trimeric HIV-1 antigens with self-assembling nanoparticles.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 27349934.
- Also identified by DOI 10.1038/ncomms12041 and PMC identifier 4931238.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- HIV-1