Induction of a cytotoxic T lymphocyte (CTL) response to plasmid DNA delivered via Lipodine liposomes.
We have previously shown that liposome-mediated plasmid DNA immunisation may be a preferred alternative to the use of naked DNA. Lipodine DNA formulations consist of liposomes containing entrapped DNA plasmid by the dehydration-rehydration (DRV) method. Such liposome formulations are distinct from liposomes with externally complexed DNA in that the majority of the DNA is "internal" to the liposome structure and hence protected from DNAase degradation. Previous studies on the immune response induced by DNA vaccines entrapped in Lipodine have focused on the humoural response. In the present study, we have expanded the analysis profile in order to include the cytotoxic T lymphocyte (CTL) component of the immune response. We have analysed the immune response induced by DNA entrapped in Lipodine compared to that induced by DNA alone when delivered subcutaneously, a route of administration not normally inducing significant plasmid DNA mediated immune activation. Our results indicate that delivery of a small dose of plasmid DNA in Lipodine results in an improved antibody response to the plasmid encoded antigen and a strong antigen specific CTL response compared to that induced by DNA delivered alone.
Bacon
Andrew
A
Lipoxen Technologies Ltd, London, WC1N 1AX. a.bacon@lipoxen.com
Caparrós-Wanderley
Wilson
W
Zadi
Brahim
B
Gregoriadis
Gregory
G
D000818:Animals; D002460:Cell Line; D004247:DNA / Q000008:administration & dosage*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D008081:Liposomes / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D016685:Mitomycin / Q000494:pharmacology; D010957:Plasmids / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism*
D000939:Epitopes; D008081:Liposomes; D016685:Mitomycin; D004247:DNA