产单核细胞李氏杆菌突变株的感染动力学研究

Kinetics of mutant Listeria monocytogenes strain yzuLM1-2 in murine infection model

以BALB/c小鼠为实验动物模型,对actA基因和plcB基因双缺失的产单核细胞李氏杆菌(LM)yzuLM1-2菌株进行感染动力学研究。分别用减毒突变株yzuLM1-2和野生型菌株yzuLM4给BALB/c小鼠静脉注射或灌服,并对脏器中LM的分布动态进行测定。结果显示,在显著高于野生型菌株感染剂量的条件下注射或灌服接种后,减毒突变株组小鼠肝和脾中的LM数量迅速下降,被清除的速度显著快于野生型菌株组。溶血素(LLO)抗体的测定结果显示,减毒突变株菌能和野生型菌同样激发较高水平的抗体。小鼠免疫保护试验结果显示,减毒突变株免疫组对同种血清型LM的攻击具有较好的免疫保护力,可达100%。结果表明,yzuLM1-2突变株侵袭力下降,致病力降低,能激发较高水平的抗体产生,可以作为预防动物李氏杆菌病的候选疫苗菌株,并为用作运送外源保护性抗原的载体提供了材料。

To investigate the ability of invasion and immune response characteristics of the mutant Listeria monocytogenes （LM） strain yzuLM1-2, from which two neighboring virulence genes actA and plcB were deleted,the kinetics study was conducted in BALB/c murine infection model. After the BALB/c mice were inoculated venously or orally with the attenuated mutant strain yzuLM1-2 or wild strain yzuLM4, bacterial amounts in the spleen and liver were measured. The mutant bacteria were fewer in the spleen and liver and cleared quicker than the wild type strain,whether by intravenous or oral inoculation. LLO antibody level in murine sera were not significantly different between the mutant strain and the wild type, which showed that the mutant strain still retain the ability to stimulate high level antibody similar to the wild type strain. All of the mice immunized with the mutant yzuLM1-2 strain were protected after challenged with the homologous wild strain yzuLM4. The result revealed that the mutant strain yzuLM1-2 characterized by low virulence, high safety, reduced ability of invasion and was able to provide effective protection against the homogenous LM challenge. The mutant strain yzuLM1-2 may provide a useful vaccine candidate against listeriosis, and could be used as a vaccine vector delivering protection antigens against human and animal diseases.