title: Selective enhancement of the type 1 cytokine response by expression of a canine interleukin (IL)-12 fused heterodimeric DNA.
abstract: Interleukin-12 (IL-12) is a heterodimeric cytokine that is a principal mediator of the innate immune response and modulator of acquired cell-mediated immunity. Administration of exogenous IL-12 can direct the host adaptive T cell response toward a type 1 phenotype. The co-administration of IL-12 with vaccine antigens has been shown to augment the vaccine-induced T(H)1 response and protection against intracellular pathogens. We show here that a canine IL-12 DNA, constructed by fusing the p35 and p40 subunit cDNAs with an interspacing linker, generated stable IL-12 transcripts when placed under control of a strong constitutive promoter. The protein expressed from this fused cDNA was fully functional in promoting a type 1 (IFN-gamma) and suppressing a type 2 (IL-4) cytokine response following both in vitro transfection of a canine cell line and in vivo delivery to dogs. This DNA construct may be useful as an adjuvant for vaccines that target tumors or intracellular pathogens of the dog.
authors.affiliation: Research Service, Department of Veterans Affairs Medical Center, South Texas Veterans Health Care System, San Antonio, TX 78229-4404, USA.
authors.forename: Omar A
authors.initials: OA
authors.lastname: Saldarriaga
authors.forename: Luis E
authors.initials: LE
authors.lastname: Perez
authors.forename: Bruno L
authors.initials: BL
authors.lastname: Travi
authors.forename: Peter C
authors.initials: PC
authors.lastname: Melby
mesh_terms: D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000276:immunology*; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004283:Dog Diseases / Q000517:prevention & control; D004285:Dogs; D015870:Gene Expression; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D053762:Interleukin-12 Subunit p40; D015847:Interleukin-4 / Q000378:metabolism; D007896:Leishmaniasis / Q000517:prevention & control / Q000662:veterinary; D008264:Macrophages / Q000378:metabolism; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology
chemical_list: D016207:Cytokines; D053762:Interleukin-12 Subunit p40; D021122:Protein Subunits; D019444:Vaccines, DNA; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma; D004247:DNA