|Title||Presenting native-like trimeric HIV-1 antigens with self-assembling nanoparticles.|
|Publication Type||Journal Article|
|Year of Publication||2016|
|Authors||He 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|
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.
|Alternate Journal||Nat Commun|
|Grant List||P01 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
Presenting native-like trimeric HIV-1 antigens with self-assembling nanoparticles.