Live attenuated Salmonella enterica serovar Typhimurium expressing swine interferon-α has antiviral activity and alleviates clinical signs induced by infection with transmissible gastroenteritis virus in piglets

Enhancing innate and acquired immunity by cytokines such as IFN-alpha appears to be useful as a first line of defense against viral infection. However, the practical use of cytokines in livestock is not evident due to cost and production issues associated with mass administration. In this study, we tested the efficacy of live attenuated Salmonella enterica serovar Typhimurium designed to secrete swine IFN-alpha (swIFN-alpha) protein for preventing the clinical signs caused by infection with transmissible gastroenteritis virus (TGEV), one of the diarrhea-causing viruses in the swine industry. Attenuated Salmonella vaccine (chi 8501) containing swIFN-alpha-encoding pYA3560 vector (chi 8501/swIFN-alpha) successfully induced the secretion of swIFN-a protein into the culture supernatants, as confirmed by SDS-PAGE and Western blot. The culture supernatants of chi 8501/swIFN-alpha had antiviral activity against TGEV with 50% effective dose (ED50) of 320 per mg of supernatant protein. In addition, oral administration of chi 8501/swIFN-alpha reduced the severity of clinical signs caused by TGEV infection with the effect more apparent at 6-8 days post-infection, and reduced excretion of TGEV in feces. Similarly, the amount of TGEV in intestinal tissues and mesenteric lymph node of chi 8501/swIFN-alpha-administered piglets was lower than in piglets that were treated with control bacteria. These results indicate the value of attenuated Salmonella vaccines as delivery systems of cytokines that can be used for mass administration, thereby overcoming cost and production issues. (C) 2010 Elsevier Ltd. All rights reserved.