Protective immune responses elicited in mice by immunization with formulations of poly(lactide-co-glycolide) microparticles.
Parenteral administration of microparticle encapsulated DNA elicits immune responses to the encoded antigens. Experiments were performed to test whether the addition of certain lipophilic agents to such formulations enhanced the activity of a beta-galactosidase (beta-gal) DNA vaccine. Addition of either taurocholic acid (TA) or monomethoxy polyethylene-glycol-distearoylphosphatidylehanolamine (PEG-DSPE) increased the efficiency of DNA encapsulation. Immunization of mice with encapsulated DNA formulations containing either compound significantly increased the number of antibody positive responders over that achieved with non-lipid containing particles. Moreover, responding animals demonstrated trends towards higher antibody titers and increased T cell responses. Tumor protection against the CT26.CL25 tumor cell line was demonstrated with lipid and non-lipid containing formulations. These results are the first demonstration of protection obtained by parenteral administration of PLG encapsulated DNA vaccines.
McKeever
U
U
Zycos Inc., 44 Hartwell Avenue, Lexington, MA 02421, USA.
Barman
S
S
Hao
T
T
Chambers
P
P
Song
S
S
Lunsford
L
L
Hsu
Y-Y
YY
Roy
K
K
Hedley
M L
ML
D000818:Animals; D000917:Antibody Formation; D019496:Cancer Vaccines / Q000008:administration & dosage; D002460:Cell Line; D004269:DNA, Bacterial / Q000235:genetics; D016503:Drug Delivery Systems; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D007114:Immunization / Q000379:methods*; D007763:Lac Operon; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D009374:Neoplasms, Experimental / Q000276:immunology / Q000517:prevention & control; D010316:Particle Size; D011098:Polyglactin 910 / Q000008:administration & dosage*; D013601:T-Lymphocytes / Q000276:immunology; D014407:Tumor Cells, Cultured; D019444:Vaccines, DNA / Q000008:administration & dosage*; D001616:beta-Galactosidase / Q000235:genetics / Q000276:immunology
D019496:Cancer Vaccines; D004269:DNA, Bacterial; D015395:Histocompatibility Antigens Class I; D019444:Vaccines, DNA; D011098:Polyglactin 910; D001616:beta-Galactosidase