He, Linlingde Val, NataliaMorris, Charles D.Vora, NemilThinnes, Therese C.Kong, LeopoldAzadnia, ParisaSok, DevinZhou, BinBurton, Dennis R.Wilson, Ian ANemazee, DavidWard, Andrew B.Zhu, Jiang2016-08-092016He, L., N. de Val, C. D. Morris, N. Vora, T. C. Thinnes, L. Kong, P. Azadnia, et al. 2016. “Presenting native-like trimeric HIV-1 antigens with self-assembling nanoparticles.” Nature Communications 7 (1): 12041. doi:10.1038/ncomms12041. http://dx.doi.org/10.1038/ncomms12041.2041-1723http://nrs.harvard.edu/urn-3:HUL.InstRepos:27822120Structures 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.en-USJournal Article2016-08-0910.1038/ncomms12041