Abstract |
Foot-and-mouth disease virus (FMDV) causes a highly contagious disease of cloven-hoofed animals. Vaccines require ∼7 days to induce protection; thus, before this time, vaccinated animals are still susceptible to the disease. Our group has previously shown that swine inoculated with 1×10(11) focus forming units (FFU) of a replication-defective human adenovirus containing the gene for porcine interferon alpha (Adt-pIFN-α) are sterilely protected from FMDV serotypes A24, O1 Manisa, or Asia 1 when the animals are challenged 1 day postadministration, and protection can last for 3-5 days. Polyriboinosinic-polyribocytidylic acid stabilized with poly- l-lysine and carboxymethyl cellulose ( poly ICLC) is a synthetic double-stranded RNA that is a viral mimic and activates multiple innate immune pathways through interaction with toll-like receptor 3 and MDA-5. It is a potent inducer of IFNs. In this study, we initially examined the effect of poly IC and IFN-α on FMDV replication and gene induction in cell culture. Poly ICLC alone or combined with Adt-pIFN-α was then evaluated for its therapeutic efficacy in swine against intradermal challenge with FMDV A24, 1 day post-treatment. Groups of swine were subcutaneously inoculated either with poly ICLC alone (4 or 8 mg) or in combination with different doses of Adt-pIFN-α (2.5×10(9), 1×10(9), or 2.5×10(8) FFU). While different degrees of protection were achieved in all the treated animals, a dose of 8 mg of poly ICLC alone or combined with 1×10(9) FFU of Adt-pIFN-α was sufficient to sterilely protect swine when challenged 24 h later with FMDV A24. IFN-stimulated gene (ISG) expression in peripheral blood mononuclear cells at 1 day post-treatment was broader and higher in protected animals than in nonprotected animals. These data indicate that poly ICLC is a potent stimulator of IFN and ISGs in swine and at an adequate dose is sufficient to induce complete protection against FMD.
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Authors | Camila C Dias, Mauro P Moraes, Marcelo Weiss, Fayna Diaz-San Segundo, Eva Perez-Martin, Andres M Salazar, Teresa de los Santos, Marvin J Grubman |
Journal | Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research
(J Interferon Cytokine Res)
Vol. 32
Issue 10
Pg. 462-73
(Oct 2012)
ISSN: 1557-7465 [Electronic] United States |
PMID | 22924938
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Adjuvants, Immunologic
- Antiviral Agents
- Interferon Inducers
- Interferon Regulatory Factors
- Interferon-alpha
- Polylysine
- poly ICLC
- Carboxymethylcellulose Sodium
- Poly I-C
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Topics |
- Adenoviridae
- Adjuvants, Immunologic
(administration & dosage)
- Animals
- Antiviral Agents
(therapeutic use)
- Biological Therapy
(methods)
- Carboxymethylcellulose Sodium
(administration & dosage, analogs & derivatives)
- Cells, Cultured
- Foot-and-Mouth Disease
(immunology, therapy)
- Foot-and-Mouth Disease Virus
- Genetic Vectors
- Humans
- Immunity, Innate
- Interferon Inducers
(administration & dosage)
- Interferon Regulatory Factors
(genetics, metabolism)
- Interferon-alpha
(genetics)
- Leukocytes, Mononuclear
(immunology, metabolism, virology)
- Poly I-C
(administration & dosage)
- Polylysine
(administration & dosage, analogs & derivatives)
- Swine
- Transgenes
(genetics)
- Virus Replication
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