Effects of IL-12 on immune responses induced by transcutaneous immunization with antigens formulated in a novel lipid-based biphasic delivery system.
The development of non-invasive methods for the delivery of proteins through the permeability barriers, such as the intact skin, will greatly facilitate the administration of human and veterinary vaccines. In the present study we used recombinant Pasteurella haemolytica leukotoxin (Lkt) and hen egg lysozyme (HEL) as model antigens to investigate the ability of transdermal administration of vaccine antigens to induce humoral and cellular responses in mice and to assess the immunomodulatory effects of IL-12 on these antigen-specific immune responses. Mice were immunized by the transdermal route with Lkt or HEL formulated in a novel lipid-based biphasic delivery system (BPDS). Transdermal delivery of Lkt or HEL induced strong polarized Th2 responses characterized by enhancement of antigen-specific IgG1 antibody subclass and predominant induction of antigen specific IL-4 over IFN-gamma in spleen and draining lymph nodes cells. Animals immunized by topical application of formulations containing antigen and IL-12 developed significantly lower antibody titres without significant changes in IL-4 or IFN-gamma secreting cells (SC) in the draining lymph nodes or spleen cells. Our results indicated that application of antigens formulated in BPDS induced antigen-specific immune responses. Furthermore, incorporation of IL-12 to the vaccine formulation influences the induction of antibody responses induced by transdermal immunization. We demonstrated the feasibility of using this technology for the development of non-invasive methods of vaccine administration.
Baca-Estrada
M E
ME
Veterinary Infectious Disease Organization, 120 Veterinary Rd, University of Saskatchewan, Saskatoon, Canada. baca@sask.usask.ca
Foldvari
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M
Ewen
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Badea
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Babiuk
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LA
D000279:Administration, Cutaneous; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D000942:Antigens, Bacterial / Q000008:administration & dosage* / Q000276:immunology; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems; D000939:Epitopes / Q000187:drug effects; D005098:Exotoxins / Q000008:administration & dosage* / Q000276:immunology; D005260:Female; D007111:Immunity, Cellular / Q000187:drug effects; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000008:administration & dosage*; D015847:Interleukin-4 / Q000096:biosynthesis; D008055:Lipids / Q000008:administration & dosage*; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009113:Muramidase / Q000008:administration & dosage* / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D000942:Antigens, Bacterial; D004337:Drug Carriers; D000939:Epitopes; D005098:Exotoxins; D007074:Immunoglobulin G; D008055:Lipids; C018579:leukotoxin; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma; D009113:Muramidase