title: Use of intranasal IL-12 to target predominantly Th1 responses to nasal and Th2 responses to oral vaccines given with cholera toxin.
abstract: We have investigated the effects of IL-12 and cholera toxin (CT) on the immune response to tetanus toxoid (TT) given by intranasal or oral routes. CT inhibited IL-12-induced IFN-gamma secretion both in vivo and in vitro. Intranasal administration of IL-12 to mice nasally immunized with the combined vaccine of TT and CT resulted in increased TT-specific IgG2a and IgG3 Abs, while IgG1 and IgE Ab responses were markedly reduced. This shift of the CT-induced immune response toward Th1 type was associated with TT-specific CD4+ T cells secreting IFN-gamma and reduced levels of Th2-type cytokines (i.e., IL-4, IL-5, IL-6, and IL-10). In contrast, intranasal IL-12 enhanced the CT-induced serum IgG1 and IgE Ab responses in mice given the combined vaccine orally. IFN-gamma secretion by TT-specific CD4+ T cells was also enhanced; however, Th2-type cytokine responses were predominant. Mucosal secretory IgA responses to oral or nasal vaccines were not affected by intranasal IL-12. Thus, intranasal IL-12 delivery influences Th cell subset development in mucosal inductive sites that are dependent on the route of vaccine delivery.
authors.affiliation: Department of Microbiology, Immunobiology Vaccine Center, University of Alabama Medical Center, Birmingham 35294-2170, USA.
authors.forename: M
authors.initials: M
authors.lastname: Marinaro
authors.forename: P N
authors.initials: PN
authors.lastname: Boyaka
authors.forename: R J
authors.initials: RJ
authors.lastname: Jackson
authors.forename: F D
authors.initials: FD
authors.lastname: Finkelman
authors.forename: H
authors.initials: H
authors.lastname: Kiyono
authors.forename: E
authors.initials: E
authors.lastname: Jirillo
authors.forename: J R
authors.initials: JR
authors.lastname: McGhee
mesh_terms: D000281:Administration, Intranasal; D000284:Administration, Oral; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D015704:CD4 Antigens / Q000276:immunology; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000008:administration & dosage / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000008:administration & dosage* / Q000276:immunology; D008081:Liposomes / Q000008:administration & dosage / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009297:Nasal Mucosa / Q000276:immunology* / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013745:Tetanus Toxoid / Q000008:administration & dosage / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D017778:Vaccines, Combined / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D015704:CD4 Antigens; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D008081:Liposomes; D013745:Tetanus Toxoid; D017778:Vaccines, Combined; D018664:Interleukin-12; D007371:Interferon-gamma; D002772:Cholera Toxin