College of Veterinary Medicine, Chonbuk National University, Jeonju, Republic of Korea.
Infect Immun. 2012 Apr;80(4):1502-9. doi: 10.1128/IAI.06264-11. Epub 2012 Jan 30.
A new strategy to develop an effective vaccine is essential to control food-borne Salmonella enterica serovar Enteritidis infections. Bacterial ghosts (BGs), which are nonliving, Gram-negative bacterial cell envelopes, are generated by expulsion of the cytoplasmic contents from bacterial cells through controlled expression using the modified cI857/λ P(R)/gene E expression system. In the present study, the pJHL99 lysis plasmid carrying the mutated lambda pR37-cI857 repressor and PhiX174 lysis gene E was constructed and transformed in S. Enteritidis to produce a BG. Temperature induction of the lysis gene cassette at 42°C revealed quantitative killing of S. Enteritidis. The S. Enteritidis ghost was characterized using scanning and transmission electron microscopy to visualize the transmembrane tunnel structure and loss of cytoplasmic materials, respectively. The efficacy of the BG as a vaccine candidate was evaluated in a chicken model using 60 10-day-old chickens, which were divided into four groups (n = 15), A, B, C, and D. Group A was designated as the nonimmunized control group, whereas the birds in groups B, C, and D were immunized via the intramuscular, subcutaneous, and oral routes, respectively. The chickens from all immunized groups showed significant increases in plasma IgG and intestinal secretory IgA levels. The lymphocyte proliferation response and CD3(+) CD4(+) and CD3(+) CD8(+) T cell subpopulations were also significantly increased in all immunized groups. The data indicate that both humoral and cell-mediated immune responses are robustly stimulated. Based on an examination of the protection efficacy measured by observations of gross lesions in the organs and bacterial recovery, the candidate vaccine can provide efficient protection against virulent challenge.
开发有效疫苗的新策略对于控制食源性肠炎沙门氏菌血清型肠炎感染至关重要。细菌体(BGs)是通过使用修饰后的 cI857/λ P(R)/基因 E 表达系统控制细胞质内容物的排出从细菌细胞中产生的非生活革兰氏阴性细菌细胞包膜。在本研究中,构建了携带突变的 lambda pR37-cI857 阻遏物和 PhiX174 裂解基因 E 的 pJHL99 裂解质粒,并转化到肠炎沙门氏菌中以产生 BG。在 42°C 时诱导裂解基因盒的温度诱导显示出肠炎沙门氏菌的定量杀伤。通过扫描和透射电子显微镜观察分别观察到跨膜隧道结构和细胞质物质的损失来表征肠炎沙门氏菌体。通过使用 60 只 10 日龄鸡的鸡模型评估 BG 作为疫苗候选物的功效,将这些鸡分为四组(n = 15),A、B、C 和 D。A 组被指定为非免疫对照组,而 B、C 和 D 组的鸟类分别通过肌肉内、皮下和口服途径免疫。所有免疫组的鸡的血浆 IgG 和肠道分泌型 IgA 水平均显着增加。淋巴细胞增殖反应以及 CD3(+) CD4(+)和 CD3(+) CD8(+) T 细胞亚群也在所有免疫组中显着增加。数据表明,体液和细胞介导的免疫反应均得到了有力的刺激。根据观察器官的大体病变和细菌回收来评估保护效力,候选疫苗可以对强毒攻击提供有效的保护。