National Centre for Zoonosis Research & Department of Infection Biology, Institute for Infection & Global Health, University of Liverpool, Neston, UK.
Avian Pathol. 2012;41(1):77-82. doi: 10.1080/03079457.2011.640305.
Salmonella enterica serovar Enteritidis is the most common cause of human salmonellosis in many developed nations. It is frequently associated with both poultry meat and eggs. In the present study we have determined whether CpG oligonucleotides that stimulate the immune system via Toll like-receptors 15 and 21 in the chicken can be used as immunomodulatory agents to break carriage of S. Enteritidis in in vitro and in vivo infection models. We also investigated its use as a component in an adjuvant to stimulate cell mediated immunity with a killed vaccine preparation. Following infection of the chicken macrophage-like cell line HD11 with Salmonella enterica serovar Gallinarum, cells were stimulated with an oligonucleotide containing a CpG motif, or with a non-CpG oligonucleotide control at concentrations ranging from 0 to 80 µM. Addition of the CpG oligonucleotide greatly enhanced clearance of S. Enteritidis in dose-dependent manner, whilst the control oligonucleotide had no significant effect. In contrast, stimulation of cells infected with S. Gallinarum had no effect. The CpG or control oligonucleotide with recombinant chicken interferon-γ was administered intramuscularly into chickens experimentally colonized with S. Enteritidis, although neither preparation produced any change in intestinal colonization levels to that in untreated control birds. Finally, CpG oligonucleotides were incorporated with recombinant interferon-γ, double-stranded RNA (Poly I:C) and squalene as a Th1-stimulating combined adjuvant for synergistic activation of cellular immunity (CASAC) together with whole killed Salmonella as the antigen as an experimental vaccine. Following vaccination and challenge of chickens with S. Enteritidis, CASAC gave significant protection to intestinal colonization whereas the same antigen given with a proprietary adjuvant did not. Neither adjuvant increased protection to systemic infection. The data suggest that adjuvants incorporating CpG motifs and interferon-γ may improve protection afforded by killed-Salmonella vaccines.
肠炎沙门氏菌血清型肠炎亚种是许多发达国家人类沙门氏菌病的最常见原因。它经常与家禽肉和鸡蛋有关。在本研究中，我们确定了是否可以使用通过 Toll 样受体 15 和 21 刺激鸡的免疫系统的 CpG 寡核苷酸作为免疫调节剂，以打破体外和体内感染模型中肠炎沙门氏菌的携带。我们还研究了将其用作佐剂的一部分，以刺激用灭活疫苗制剂进行细胞介导的免疫。在沙门氏菌鸡马立克氏细胞系 HD11 感染鸡后，用含有 CpG 基序的寡核苷酸或非 CpG 寡核苷酸对照物在 0 至 80µM 的浓度刺激细胞。CpG 寡核苷酸的添加以剂量依赖性方式大大增强了肠炎沙门氏菌的清除，而对照寡核苷酸则没有显着影响。相反，刺激感染了肠炎沙门氏菌的细胞没有效果。CpG 或对照寡核苷酸与重组鸡干扰素-γ 一起肌内注射到实验性感染肠炎沙门氏菌的鸡中，尽管两种制剂都没有使未处理的对照鸟类的肠道定植水平发生任何变化。最后，CpG 寡核苷酸与重组干扰素-γ、双链 RNA（Poly I:C）和角鲨烯一起作为 Th1 刺激联合佐剂（CASAC）与整个灭活的沙门氏菌一起作为抗原作为实验疫苗，以协同激活细胞免疫。接种疫苗并对鸡进行肠炎沙门氏菌攻毒后，CASAC 对肠道定植提供了显着的保护作用，而相同的抗原与专有佐剂一起使用则没有。两种佐剂均未增加对全身感染的保护。数据表明，包含 CpG 基序和干扰素-γ 的佐剂可能会改善灭活沙门氏菌疫苗提供的保护。
