College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University, Jeonju 561-756, Republic of Korea.
Vaccine. 2010 Jul 12;28(31):5031-7. doi: 10.1016/j.vaccine.2010.05.013. Epub 2010 May 18.
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.
通过细胞因子（如 IFN-α）增强先天和获得性免疫似乎是抵抗病毒感染的第一道防线。然而，由于大规模给药相关的成本和生产问题，细胞因子在畜牧业中的实际应用并不明显。在这项研究中，我们测试了设计用于分泌猪干扰素-α（swIFN-α）蛋白的减毒鼠伤寒沙门氏菌血清型 Typhimurium（Salmonella enterica serovar Typhimurium）对预防传染性胃肠炎病毒（TGEV）感染引起的临床症状的功效，TGEV 是猪产业中引起腹泻的病毒之一。含有编码 swIFN-α 的 pYA3560 载体的减毒沙门氏菌疫苗（chi8501/swIFN-α）（chi8501）成功地诱导 swIFN-α 蛋白分泌到培养上清液中，这一点通过 SDS-PAGE 和 Western blot 得到了证实。chi8501/swIFN-α 的培养上清液对 TGEV 具有抗病毒活性，其对 TGEV 的 50%有效剂量（ED（50））为每毫克上清蛋白 320。此外，口服 chi8501/swIFN-α 减轻了 TGEV 感染引起的临床症状的严重程度，在感染后 6-8 天效果更为明显，并且减少了 TGEV 在粪便中的排泄。同样，给予 chi8501/swIFN-α 的仔猪的肠道组织和肠系膜淋巴结中的 TGEV 数量低于用对照细菌治疗的仔猪。这些结果表明，减毒沙门氏菌疫苗作为细胞因子的递送系统具有价值，可用于大规模给药，从而克服成本和生产问题。
