Coating of cationized protein on engineered nanoparticles results in enhanced immune responses.
A significant emphasis has been placed on the development of improved adjuvants and delivery systems to improve both antibody production and cell-mediated immunity. The overall goal of this project was to cationize a model protein antigen, beta-galactosidase (nGal), coat the cationized Gal (cGal) on the surface of novel anionic nanoparticles engineered from microemulsion precursors, and assess the immune response of this system after subcutaneous injection to mice. Gal was chemically cationized as evidenced by gel electrophoresis. The cGal was coated on anionic nanoparticles (78+/-11 nm) engineered from oil-in-water microemulsion precursors to produce cGal-coated nanoparticles. The immune response to nGal with 'Alum', cGal alone, and cGal-coated nanoparticles were assessed after subcutaneous injection to Balb/c mice. cGal alone elicited similar antibody titer to nGal with 'Alum'. However, cGal-coated nanoparticles elicited the strongest and most reproducible antibody titer. cGal alone produced very high levels of Th1 cytokines, but low levels of Th2 cytokines. In contrast, cGal-coated nanoparticles significantly enhanced both the Th1 and Th2 cytokines. The results demonstrated the utility of antigen-coated nanoparticles to enhance both the humoral and Th1-type immune responses, in parallel.
Cui
Zhengrong
Z
Division of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0082, USA.
Mumper
Russell J
RJ
D000276:Adjuvants, Immunologic / Q000737:chemistry*; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology; D002412:Cations; D016207:Cytokines / Q000096:biosynthesis; D004655:Emulsions; D005260:Female; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D008863:Microspheres; D010316:Particle Size; D011506:Proteins / Q000737:chemistry* / Q000276:immunology*; D012967:Sodium Dodecyl Sulfate; D012996:Solutions; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013501:Surface-Active Agents; D013535:Suspensions; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D001616:beta-Galactosidase / Q000737:chemistry / Q000276:immunology
D000276:Adjuvants, Immunologic; D002412:Cations; D016207:Cytokines; D004655:Emulsions; D011506:Proteins; D012996:Solutions; D013501:Surface-Active Agents; D013535:Suspensions; D012967:Sodium Dodecyl Sulfate; D001616:beta-Galactosidase