Selective enhancement of the type 1 cytokine response by expression of a canine interleukin (IL)-12 fused heterodimeric DNA.
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.
Saldarriaga
Omar A
OA
Research Service, Department of Veterans Affairs Medical Center, South Texas Veterans Health Care System, San Antonio, TX 78229-4404, USA.
Perez
Luis E
LE
Travi
Bruno L
BL
Melby
Peter C
PC
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
D016207:Cytokines; D053762:Interleukin-12 Subunit p40; D021122:Protein Subunits; D019444:Vaccines, DNA; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma; D004247:DNA