title: High-Density Array of Well-Ordered HIV-1 Spikes on Synthetic Liposomal Nanoparticles Efficiently Activate B Cells.
abstract: A major step toward an HIV-1 vaccine is an immunogen capable of inducing neutralizing antibodies. Envelope glycoprotein (Env) mimetics, such as the NFL and SOSIP designs, generate native-like, well-ordered trimers and elicit tier 2 homologous neutralization (SOSIPs). We reasoned that the display of well-ordered trimers by high-density, particulate array would increase B cell activation compared to soluble trimers. Here, we present the design of liposomal nanoparticles displaying well-ordered Env spike trimers on their surface. Biophysical analysis, cryo- and negative stain electron microscopy, as well as binding analysis with a panel of broadly neutralizing antibodies confirm a high-density, well-ordered trimer particulate array. The Env-trimer-conjugated liposomes were superior to soluble trimers in activating B cells ex vivo and germinal center B cells in vivo. In addition, the trimer-conjugated liposomes elicited modest tier 2 homologous neutralizing antibodies. The trimer-conjugated liposomes represent a promising initial lead toward the development of more effective HIV vaccine immunogens.
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Jidnyasa
authors.initials: J
authors.lastname: Ingale
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Armando
authors.initials: A
authors.lastname: Stano
authors.affiliation: IAVI Neutralizing Antibody Center at The Scripps Research Institute (TSRI), La Jolla, CA 92037, USA.
authors.forename: Javier
authors.initials: J
authors.lastname: Guenaga
authors.affiliation: IAVI Neutralizing Antibody Center at The Scripps Research Institute (TSRI), La Jolla, CA 92037, USA.
authors.forename: Shailendra Kumar
authors.initials: SK
authors.lastname: Sharma
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: David
authors.initials: D
authors.lastname: Nemazee
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Zwick
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center at The Scripps Research Institute (TSRI), La Jolla, CA 92037, USA. Electronic address: wyatt@scripps.edu.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Wyatt
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D015483:HIV Antibodies / Q000276:immunology; D015497:HIV-1 / Q000378:metabolism*; D007368:Interferometry; D008081:Liposomes / Q000737:chemistry* / Q000648:ultrastructure; D008213:Lymphocyte Activation / Q000276:immunology*; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D055503:Protein Multimerization; D011817:Rabbits; D012995:Solubility; D013696:Temperature; D054299:env Gene Products, Human Immunodeficiency Virus / Q000737:chemistry*
chemical_list: D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D008081:Liposomes; D054299:env Gene Products, Human Immunodeficiency Virus