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Mechanisms of increased immunogenicity for DNA-based vaccines adsorbed onto cationic microparticles.
- Source :
-
Cellular immunology [Cell Immunol] 2003 Sep; Vol. 225 (1), pp. 12-20. - Publication Year :
- 2003
-
Abstract
- Investigation into the mechanism of action of vaccine adjuvants provides opportunities to define basic immune principles underlying the induction of strong immune responses and insights useful for the rational development of subunit vaccines. A novel HIV vaccine composed of plasmid DNA-encoding p55 gag formulated with poly-lactide-co-glycolide microparticles (PLG) and cetyl trimethyl ammonium bromide (CTAB) elicits both serum antibody titers and cytotoxic lymphocyte activity in mice at doses two orders of magnitude lower than those required for comparable response to plasmid DNA in saline. Using this model, we demonstrated the increase in potency requires the DNA to be complexed to the PLG-CTAB microparticles. Furthermore, the PLG-CTAB-DNA formulation increased the persistence of DNA at the injection site, recruited mononuclear phagocytes to the site of injection, and activated a population of antigen presenting cells. Intramuscular immunization with the PLG-CTAB-DNA complex induced antigen expression at both the injection site and the draining lymph node. These findings demonstrate that the PLG-CTAB-DNA formulation exhibits multiple mechanisms of immunopotentiation.
- Subjects :
- AIDS Vaccines chemistry
AIDS Vaccines genetics
AIDS Vaccines pharmacokinetics
Adjuvants, Immunologic chemistry
Adjuvants, Immunologic pharmacokinetics
Animals
Anti-Infective Agents pharmacology
Antigens, Viral immunology
Cetrimonium
Cetrimonium Compounds pharmacokinetics
Cetrimonium Compounds pharmacology
DNA, Viral genetics
DNA, Viral immunology
Female
Gene Products, gag genetics
HIV Infections immunology
HIV Infections prevention & control
HIV-1 genetics
Mice
Mice, Inbred BALB C
Microscopy, Fluorescence
Microspheres
Polyglactin 910 chemistry
Polyglactin 910 pharmacokinetics
Polyglactin 910 pharmacology
Reverse Transcriptase Polymerase Chain Reaction
Vaccines, DNA chemistry
Vaccines, DNA genetics
Vaccines, DNA pharmacokinetics
AIDS Vaccines immunology
Adjuvants, Immunologic pharmacology
Gene Products, gag immunology
HIV-1 immunology
Vaccines, DNA immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0008-8749
- Volume :
- 225
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Cellular immunology
- Publication Type :
- Academic Journal
- Accession number :
- 14643300
- Full Text :
- https://doi.org/10.1016/j.cellimm.2003.09.003