College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University, Jeonju 561-756, Korea.
Microbiol Immunol. 2012 Aug;56(8):529-40. doi: 10.1111/j.1348-0421.2012.00473.x.
The co-administration of two or more cytokines may generate additive or synergistic effects for controlling infectious diseases. However, the practical use of cytokine combinations for the modulation of immune responses against inactivated vaccine has not been demonstrated in livestock yet, primarily due to protein stability, production, and costs associated with mass administration. In light of the current situation, we evaluated the immunomodulatory functions of the combined administration of swine interleukin-18 (swIL-18) and interferon-α (swIFN-α) against an inactivated PrV vaccine using attenuated Salmonella enterica serovar Typhimurium as a cytokine delivery system. Co-administration of S. enterica serovar Typhimurium expressing swIL-18 and swIFN-α produced enhanced Th1-biased humoral and cellular immune responses against the inactivated PrV vaccine, when compared to single administration of S. enterica serovar Typhimurium expressing either swIL-18 or swIFN-α. Also, enhanced immune responses in co-administered piglets occurred rapidly after virulent PrV challenge, and piglets that received co-administration of S. enterica serovar Typhimurium expressing swIL-18 and swIFN-α displayed a greater alleviation of clinical severity following the virulent PrV challenge, as determined by clinical scores and cumulative daily weight gain. Furthermore, this enhancement was confirmed by reduced nasal shedding of PrV following viral challenge. Therefore, these results suggest that oral co-administration of S. enterica serovar Typhimurium expressing swIL-18 and swIFN-α provide enhanced Th1-biased immunity against inactivated PrV vaccine to alleviate clinical signs caused by PrV challenge.
两种或多种细胞因子的联合应用可能产生针对控制传染病的附加或协同作用。然而，细胞因子联合应用于调节针对灭活疫苗的免疫反应在畜牧业中尚未得到实际应用，主要是由于与大规模应用相关的蛋白质稳定性、生产和成本问题。鉴于目前的情况，我们评估了猪白细胞介素-18（swIL-18）和干扰素-α（swIFN-α）联合应用对减毒鼠伤寒沙门氏菌作为细胞因子递送系统的灭活 PrV 疫苗的免疫调节功能。与单独施用表达 swIL-18 或 swIFN-α 的鼠伤寒沙门氏菌相比，施用表达 swIL-18 和 swIFN-α 的鼠伤寒沙门氏菌联合可增强针对灭活 PrV 疫苗的 Th1 偏向性体液和细胞免疫反应。此外，在强毒 PrV 攻毒后，共同给药仔猪的免疫反应迅速增强，并且接受表达 swIL-18 和 swIFN-α 的鼠伤寒沙门氏菌共同给药的仔猪在强毒 PrV 攻毒后临床严重程度的缓解更为明显，这是通过临床评分和累积每日体重增加来确定的。此外，通过病毒攻毒后 PrV 的鼻腔脱落减少证实了这种增强。因此，这些结果表明，减毒鼠伤寒沙门氏菌表达 swIL-18 和 swIFN-α 的口服共同给药可增强针对灭活 PrV 疫苗的 Th1 偏向性免疫，从而缓解 PrV 攻毒引起的临床症状。
