title: Strong antibody responses induced by protein antigens conjugated onto the surface of lecithin-based nanoparticles.
abstract: An accumulation of research over the years has demonstrated the utility of nanoparticles as antigen carriers with adjuvant activity. Herein we defined the adjuvanticity of a novel lecithin-based nanoparticle engineered from emulsions. The nanoparticles were spheres of around 200nm. Model protein antigens, bovine serum albumin (BSA) or Bacillus anthracis protective antigen (PA) protein, were covalently conjugated onto the nanoparticles. Mice immunized with the BSA-conjugated nanoparticles developed strong anti-BSA antibody responses comparable to that induced by BSA adjuvanted with incomplete Freund's adjuvant and 6.5-fold stronger than that induced by BSA adsorbed onto aluminum hydroxide. Immunization of mice with the PA-conjugated nanoparticles elicited a quick, strong, and durable anti-PA antibody response that afforded protection of the mice against a lethal dose of anthrax lethal toxin challenge. The potent adjuvanticity of the nanoparticles was likely due to their ability to move the antigens into local draining lymph nodes, to enhance the uptake of the antigens by antigen-presenting cells (APCs), and to activate APCs. This novel nanoparticle system has the potential to serve as a universal protein-based vaccine carrier capable of inducing strong immune responses.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR 97331, United States.
authors.forename: Brian R
authors.initials: BR
authors.lastname: Sloat
authors.forename: Michael A
authors.initials: MA
authors.lastname: Sandoval
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Hau
authors.forename: Yongqun
authors.initials: Y
authors.lastname: He
authors.forename: Zhengrong
authors.initials: Z
authors.lastname: Cui
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000187:drug effects* / Q000276:immunology; D000942:Antigens, Bacterial / Q000008:administration & dosage* / Q000276:immunology; D001427:Bacterial Toxins / Q000008:administration & dosage* / Q000276:immunology; D002460:Cell Line; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D004355:Drug Stability; D004655:Emulsions; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007114:Immunization; D054709:Lecithins / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D009500:Neutralization Tests; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D012710:Serum Albumin, Bovine / Q000008:administration & dosage* / Q000276:immunology; D013499:Surface Properties
chemical_list: D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D004337:Drug Carriers; D004655:Emulsions; D054709:Lecithins; D011994:Recombinant Proteins; C030325:anthrax toxin; D012710:Serum Albumin, Bovine