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United States Department of Agriculture

Agricultural Research Service

Research Project: INTERVENTION STRATEGIES TO SUPPORT THE GLOBAL CONTROL AND ERADICATION OF FOOT-AND-MOUTH DISEASE VIRUS (FMDV)

Location: Foreign Animal Disease Research

Title: Type III interferon protects swine against foot-and-mouth disease

Authors
item Perez-Martin, Eva -
item Diaz San Segundo, Fayna
item Weiss, Marcelo -
item Sturza, Diego -
item Dias, Camila -
item Ramirez, Elizabeth -
item Grubman, Marvin -
item De Los Santos, Teresa

Submitted to: Journal of Interferon and Cytokine Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: April 18, 2014
Publication Date: April 30, 2014
Citation: Perez-Martin, E., Diaz San Segundo, F.C., Weiss, M., Sturza, D., Dias, C.C., Ramirez, E., Grubman, M.J., De Los Santos, T.B. 2014. Type III interferon protects swine against foot-and-mouth disease. Journal of Interferon and Cytokine Research. DOI:10.1089/jir.2013.0112.

Interpretive Summary: Foot and mouth disease (FMD) virus is highly contagious. Controlling FMD outbreaks requires stopping virus spread by vaccinating animals. Currently available vaccines take 7 days to induce full protection, therefore in recent years we have developed novel strategies including the use of biotherapeutics such as interferons (IFN) that when delivered by a harmless adenovirus vector (Ad5) can protect cattle and swine as early as 24 h post vaccination. Three types of IFN (I, II and III) have been described in cattle and swine. Here we have evaluated for the first time a subtype of type III IFN, porcine IFN-lambda3 (poIFN-lambda3) delivered by an Ad5 to control FMD. Swine inoculated with different doses of Ad5-poIFN-lambda3 could be protected against disease. Seven out of ten Ad5-poIFN-lambda3 inoculated animals did not develop disease or had detectable virus in blood, and the other three inoculated animals displayed delayed and milder disease by 7 days post challenge as compared to control animals inoculated with an Ad5 control vector. These results suggest that treatment with Ad5-poIFN-lambda3 is effective in inducing early protection against FMD in swine. Since current FMD vaccines can induce protection in 5-7 days, combination of the IFN therapy and vaccination could provide a valuable strategy to control FMD outbreaks in swine.

Technical Abstract: In recent years we have developed novel strategies to control foot-and-mouth disease (FMD) including the use of biotherapeutics such as interferons (IFN) delivered by a replication-defective human adenovirus type 5 (Ad5). Swine can be sterilely protected after vaccination with an Ad5 that encodes porcine type I IFN (poIFN-alpha) and cattle treated with a similar Ad5 but delivering bovine type III IFN (boIFN-lambda3) are protected or develop significantly reduced disease as compared to control animals or boIFN-alpha treated animals. Here we have evaluated the efficacy of porcine IFN-lambda3 (poIFN-lambda3) against FMD in vivo. Swine inoculated with different doses of Ad5-poIFN-lambda3 could be protected against disease in a dose dependent manner. Despite the absence of systemic antiviral activity, seven out of ten Ad5-poIFN-lambda3 inoculated animals did not develop disease or viremia and the other three inoculated animals displayed delayed and milder disease by 7 days post challenge as compared to control animals inoculated with an Ad5 control vector. However, even in the absence of clinical signs or viremia, nine out of ten Ad5-poIFN-lambda3 inoculated animals developed antibodies against FMDV structural and non structural proteins after challenge, suggesting that protection was not sterile. While analysis of gene expression showed significant induction of IFN and IFN stimulated genes in Ad5-poIFN-lambda3 treated cultured porcine epithelial kidney cells, there was limited gene induction in peripheral blood monocytes isolated from treated swine. These results suggest that treatment with Ad5-poIFN-lambda3 is an effective biotherapeutic strategy against FMD in swine.

Last Modified: 7/22/2014
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