title: Presenting native-like trimeric HIV-1 antigens with self-assembling nanoparticles.
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.
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Linling
authors.initials: L
authors.lastname: He
authors.affiliation: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California 92037, USA.|International AIDS Vaccine Initiative Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery, The Scripps Research Institute, La Jolla, California 92037, USA.|Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: Natalia
authors.initials: N
authors.lastname: de Val
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Charles D
authors.initials: CD
authors.lastname: Morris
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Nemil
authors.initials: N
authors.lastname: Vora
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Therese C
authors.initials: TC
authors.lastname: Thinnes
authors.affiliation: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California 92037, USA.|International AIDS Vaccine Initiative Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery, The Scripps Research Institute, La Jolla, California 92037, USA.|Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: Leopold
authors.initials: L
authors.lastname: Kong
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Parisa
authors.initials: P
authors.lastname: Azadnia
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, California 92037, USA.|International AIDS Vaccine Initiative Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery, The Scripps Research Institute, La Jolla, California 92037, USA.|Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: Devin
authors.initials: D
authors.lastname: Sok
authors.affiliation: Department of Chemistry, The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, California 92037, USA.|International AIDS Vaccine Initiative Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery, The Scripps Research Institute, La Jolla, California 92037, USA.|Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California 92037, USA.|Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts 02139-3583, USA.
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Burton
authors.affiliation: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California 92037, USA.|International AIDS Vaccine Initiative Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery, The Scripps Research Institute, La Jolla, California 92037, USA.|Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California 92037, USA.|The Joint Center for Structural Genomics, The Scripps Research Institute, La Jolla, California 92037, USA.|Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: Ian A
authors.initials: IA
authors.lastname: Wilson
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: David
authors.initials: D
authors.lastname: Nemazee
authors.affiliation: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California 92037, USA.|International AIDS Vaccine Initiative Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery, The Scripps Research Institute, La Jolla, California 92037, USA.|Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Ward
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, California 92037, USA.|Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California 92037, USA.|Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: Jiang
authors.initials: J
authors.lastname: Zhu
mesh_terms: D015195:Drug Design; D015497:HIV-1 / Q000276:immunology*; D053758:Nanoparticles; D014612:Vaccines
chemical_list: D014612:Vaccines