Submitted to: Journal of Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/1/2003
Publication Date: 1/1/2003
Citation: CHINSANGARAM, J., MORAES, M.P., KOSTER, M.J., GRUBMAN, M.J. A NOVEL STRATEGY TO CONTROL INFECTIOUS VIRAL DISEASES: ADENOVIRUS CONTAINING INTERFERON ALPHA PROTECTS SWINE FROM FOOT-AND-MOUTH DISEASE. JOURNAL OF VIROLOGY. V77(2):1621-1625, 2003 Interpretive Summary: Foot-and-mouth disease virus (FMDV) causes an economically devastating disease of cloven-hoofed animals. Vaccines produced by chemical inactivation of virus are available, but there are concerns about their safety and they do not induce protection prior to about 7 days postvaccination. In the event of an FMD outbreak in a disease-free country such as the US, it is necessary to induce immediate protection. We have shown that in cell culture FMDV is inhibited by type I interferon. In this manuscript, we have developed a recombinant human adenovirus as an expression vector that contains the gene for porcine interferon alpha. Swine given one inoculation of this recombinant virus and then challenged with virulent FMDV one day postinoculation were completely protected from clinical signs of disease and viremia. In addition, these animals did not develop an antibody response against viral nonstructural proteins indicating sterile protection. In contrast, control animals inoculated with an adenovirus lacking the interferon gene developed typical signs of FMD. These results demonstrate, for the first time, that a single inoculation of an Ad5-interferon virus can be used as a tool to immediately control FMD in emergency outbreak situations.
Technical Abstract: We have previously shown that replication of foot-and-mouth disease virus (FMDV) is highly sensitive to alpha/beta interferon (IFN- / ). In the present study, we constructed recombinant, replication-defective human adenovirus type 5 vectors containing either porcine IFN- or IFN- (Ad5-pIFN or Ad5-pIFN ). We demonstrated that cells infected with these viruses express high levels of biologically active IFN. Swine inoculated with 109 pfu of a control Ad5 virus lacking the IFN gene and challenged 24 hours later with FMDV developed typical signs of FMD including fever, vesicular lesions, and viremia. In contrast, swine inoculated with 109 pfu of Ad5-pIFN were completely protected when challenged 24 hours later with FMDV. These animals showed no clinical signs of FMD, no viremia, and did not develop antibodies against viral nonstructural (NS) proteins, suggesting that complete protection from infection was achieved.