Selective enhancement of the type 1 cytokine response by expression of a canine interleukin (IL)-12 fused heterodimeric DNA

Omar A. Saldarriaga; Luis E. Perez; Bruno L. Travi; Peter C. Melby

doi:10.1016/j.vetimm.2005.11.003

Selective enhancement of the type 1 cytokine response by expression of a canine interleukin (IL)-12 fused heterodimeric DNA

Omar A. Saldarriaga, Luis E. Perez, Bruno L. Travi, Peter C. Melby

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

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_H1 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-γ) 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.

Original language	English (US)
Pages (from-to)	377-388
Number of pages	12
Journal	Veterinary Immunology and Immunopathology
Volume	110
Issue number	3-4
DOIs	https://doi.org/10.1016/j.vetimm.2005.11.003
State	Published - Apr 15 2006
Externally published	Yes

Keywords

Canine
IFN-γ
Interleukin-12
Vaccine adjuvant

ASJC Scopus subject areas

Immunology
General Veterinary

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10.1016/j.vetimm.2005.11.003

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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 TH1 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-γ) 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.",

keywords = "Canine, IFN-γ, Interleukin-12, Vaccine adjuvant",

author = "Saldarriaga, {Omar A.} and Perez, {Luis E.} and Travi, {Bruno L.} and Melby, {Peter C.}",

note = "Funding Information: This work was supported by NIH grant AI48823 awarded to PCM, and Colciencias grant 2229-04-11723 awarded to BLT. The authors wish to thank Dr. Mathias Buettner for providing the canine IL-12p40 plasmid, Vical Inc. for providing the VR1051 plasmid, and James Elliott, DVM for helping to obtain the blood from the dogs.",

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language = "English (US)",

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AU - Saldarriaga, Omar A.

AU - Perez, Luis E.

AU - Travi, Bruno L.

AU - Melby, Peter C.

N1 - Funding Information: This work was supported by NIH grant AI48823 awarded to PCM, and Colciencias grant 2229-04-11723 awarded to BLT. The authors wish to thank Dr. Mathias Buettner for providing the canine IL-12p40 plasmid, Vical Inc. for providing the VR1051 plasmid, and James Elliott, DVM for helping to obtain the blood from the dogs.

PY - 2006/4/15

Y1 - 2006/4/15

N2 - 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 TH1 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-γ) 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.

AB - 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 TH1 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-γ) 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.

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KW - Interleukin-12

KW - Vaccine adjuvant

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Selective enhancement of the type 1 cytokine response by expression of a canine interleukin (IL)-12 fused heterodimeric DNA

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Keywords

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