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 (chi8501) containing swIFN-alpha-encoding pYA3560 vector (chi8501/swIFN-alpha) successfully induced the secretion of swIFN-alpha
protein into the culture supernatants, as confirmed by SDS-PAGE and Western blot. The culture supernatants of chi8501/swIFN-alpha had
antiviral activity against TGEV with 50% effective dose (ED(50)) of 320 per mg of supernatant
protein. In addition,
oral administration of chi8501/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 chi8501/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.