Topical delivery of plasmid DNA using biphasic lipid vesicles (Biphasix).
The development of non-invasive methods for the delivery of vaccines through the skin will greatly improve the safety and the administration of human and veterinary vaccines. In this study we examined the efficiency of topical delivery of plasmids by assessing the localization of gene expression using luciferase as a reporter gene and induction of immune responses using a plasmid encoding for the bovine herpesvirus type-1 glycoprotein D (pgD). Topical administration of plasmids in a lipid-based delivery system (biphasic lipid vesicles--Biphasix) resulted in gene expression in the lymph node, whereas with intradermal injection, antigen expression was found in the skin. Following administration of plasmid with the gene gun, antigen expression was observed in both the skin as well as in the draining lymph nodes. Transcutaneous immunization with pgD formulated in biphasic lipid vesicles elicited gD-specific antibody responses and a Th2-type cellular response. In contrast, immunization by the intradermal route resulted in the stimulation of a Th1-type response. These findings have implications for both vaccine design and tailoring of specific immune responses.
Babiuk
Shawn
S
College of Pharmacy and Nutrition, University of Saskatchewan, 110 Science Place, Saskatoon, Sask. S7N 5C9, Canada.
Baca-Estrada
Maria E
ME
Pontarollo
Reno
R
Foldvari
Marianna
M
D000279:Administration, Cutaneous; D000704:Analysis of Variance; D000818:Animals; D000917:Antibody Formation; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D005260:Female; D007111:Immunity, Cellular; D007271:Injections, Intradermal; D008055:Lipids; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008198:Lymph Nodes / Q000201:enzymology; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics* / Q000276:immunology
D004337:Drug Carriers; D008055:Lipids; D019444:Vaccines, DNA; D014764:Viral Proteins; C046998:bovine herpesvirus type-1 glycoproteins; D008156:Luciferases