Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Alexandria University, Egypt.
Department of Microbiology, University College Cork, Cork, Ireland.
J Med Microbiol. 2010 Aug;59(Pt 8):904-912. doi: 10.1099/jmm.0.018770-0. Epub 2010 May 20.
Listeria monocytogenes is a food-borne intracellular pathogen that mainly infects pregnant and immunocompromised individuals. The pore-forming haemolysin listeriolysin O (LLO), the main virulence factor of Listeria monocytogenes, allows bacteria to escape from the harsh environment of the phagosome to the cytoplasm of the infected cell. This leads to processing of bacterial antigens predominantly through the cytosolic MHC class I presentation pathway. We previously engineered the food-grade bacterium Lactococcus lactis to express LLO and demonstrated an LLO-specific CD8(+) response upon immunization of mice with the engineered L. lactis vaccine strains. In the present work, we examined the immune response and protective efficacy of an L. lactis strain co-expressing LLO and a truncated form of the listerial P60 antigen (tP60). Oral immunization revealed no significant protection against listeriosis with L. lactis expressing LLO, tP60 or the combined LLO/tP60. In contrast, intraperitoneal vaccination induced an LLO-specific CD8(+) immune response with LLO-expressing L. lactis but no significant improvement in protection was observed following vaccination with the combined LLO/tP60 expressing L. lactis strain. This may be due to the low level of tP60 expression in the LLO/tP60 strain. These results demonstrate the necessity for improved oral vaccination strategies using LLO-expressing L. lactis vaccine vectors.
李斯特菌是一种食源性病原体，主要感染孕妇和免疫功能低下者。细菌穿孔溶血素李斯特菌溶血素 O（LLO）是李斯特菌的主要毒力因子，使细菌能够从吞噬体的恶劣环境中逃逸到受感染细胞的细胞质中。这导致细菌抗原的加工主要通过胞质 MHC 类 I 呈递途径进行。我们之前已经将食品级细菌乳球菌工程化为表达 LLO，并在对工程化乳球菌疫苗株进行免疫的小鼠中证明了LLO 特异性 CD8+反应。在本工作中，我们研究了共表达 LLO 和李斯特菌 P60 抗原截断形式（tP60）的乳球菌株的免疫反应和保护效力。口服免疫未显示出对李斯特菌病的显著保护作用，用表达 LLO、tP60 或 LLO/tP60 的乳球菌进行免疫。相比之下，腹腔内接种用表达 LLO 的乳球菌诱导了 LLO 特异性 CD8+免疫反应，但用共表达 LLO/tP60 的乳球菌接种未观察到保护作用的显著改善。这可能是由于 LLO/tP60 株中 tP60 的表达水平较低。这些结果表明需要使用表达 LLO 的乳球菌疫苗载体改进口服疫苗接种策略。
