Cationic microparticles: A potent delivery system for DNA vaccines.
An approach involving the preparation of biodegradable microparticles with a cationic surface was developed to improve the delivery of adsorbed DNA into antigen-presenting cells after i.m. injection. The microparticles released intact and functional DNA over 2 weeks in vitro. In addition, the microparticles induced higher levels of marker gene expression in vivo. After i.m. immunization, the microparticles induced significantly enhanced serum antibody responses in comparison to naked DNA. Moreover, the level of antibodies induced by the microparticles was significantly enhanced by the addition of a vaccine adjuvant, aluminum phosphate. In addition, in contrast to naked DNA, the cationic microparticles induced potent cytotoxic T lymphocyte responses at a low dose.
Singh
M
M
Chiron Vaccines, Chiron Corporation, 4560 Horton Street, Emeryville, CA 94608, USA.
Briones
M
M
Ott
G
G
O'Hagan
D
D
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D002412:Cations; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods; D016503:Drug Delivery Systems; D015870:Gene Expression; D015683:Gene Products, gag / Q000235:genetics; D007273:Injections, Intramuscular; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D010316:Particle Size; D011498:Protein Precursors / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology
D002412:Cations; D004279:DNA, Viral; D004337:Drug Carriers; D015683:Gene Products, gag; D011498:Protein Precursors; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; C059767:p55 gag precursor protein, Human immunodeficiency virus 1; D004247:DNA; D008156:Luciferases