Live attenuated Salmonella enterica serovar Typhimurium expressing swine interferon-alpha 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 (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.
Kim
Seon Ju
SJ
College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University, Jeonju 561-756, Republic of Korea.
Han
Young Woo
YW
Rahman
Md Masudur
MM
Kim
Seong Bum
SB
Uyangaa
Erdenebileg
E
Lee
Byung Min
BM
Kim
Jin Hyoung
JH
Roh
Yoon Seok
YS
Kang
Seong Ho
SH
Kim
Koanhoi
K
Lee
John Hwa
JH
Kim
Bumseok
B
Park
Ki In
KI
Eo
Seong Kug
SK
D000818:Animals; D000998:Antiviral Agents / Q000276:immunology*; D005761:Gastroenteritis, Transmissible, of Swine / Q000276:immunology / Q000517:prevention & control*; D007370:Interferon Type I / Q000235:genetics / Q000276:immunology*; D010957:Plasmids; D011994:Recombinant Proteins; D012486:Salmonella typhimurium / Q000276:immunology* / Q000378:metabolism; D013552:Swine; D005760:Transmissible gastroenteritis virus / Q000276:immunology; D014613:Vaccines, Attenuated / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*; D017201:Virus Shedding
D000998:Antiviral Agents; D007370:Interferon Type I; D011994:Recombinant Proteins; D014613:Vaccines, Attenuated; D014765:Viral Vaccines