Yin Yuelan, Tian Debin, Jiao Hongmei, Zhang Chenju, Pan Zhiming, Zhang Xiaoming, Wang Xiaobo, Jiao Xinan
Jiangsu Key Laboratory of Zoonosis, Yangzhou University, 12 East Wenhui Road, Yangzhou, Jiangsu 225009, People's Republic of China.
Clin Vaccine Immunol. 2011 Mar;18(3):500-5. doi: 10.1128/CVI.00445-10. Epub 2011 Jan 12.
Listeria monocytogenes has been exploited as a vaccine carrier based upon its ability to induce a strong cell-mediated immune response. At present, the safety of live, attenuated L. monocytogenes vaccines in patients is being studied in clinical trials. L. monocytogenes is also an attractive vaccine vector for use in poultry; however, the pathogenicity and immunogenicity of this organism in poultry remain to be fully elucidated. In this study, we investigated the pathogenicity and immunogenicity of an actA- and plcB-deficient L. monocytogenes strain, yzuLM4ΔactA/plcB, and its wild-type parent strain, yzuLM4, in an avian infection model. The results showed that the wild-type strain could infect ISA brown chickens, causing serious tissue disruptions, including various degrees of degeneration, necrotic lesions, and inflammatory cell infiltration in the liver, spleen, heart, and kidney. However, the mutant strain showed reduced virulence in embryonated eggs compared with that of the parent strain (the 50% lethal dose [LD(50)] was 3 logs higher). The mutant strain also showed low virulence in chickens and was rapidly eliminated by the host. There were no obvious pathological changes in tissue sections, but the mutant strain still retained the ability to stimulate high levels of antibody against the protein listeriolysin O (LLO). Booster immunization with the mutant strain led to rapid bacterial clearance from the livers and spleens of chickens challenged by the intramuscular route or the oral route. Collectively, our data suggest that the wild-type serotype 1/2a L. monocytogenes strain can cause serious disease in chickens but the mutant strain with a deletion of the actA and plcB genes is less virulent but induces a strong immune response. This mutant strain of L. monocytogenes is therefore a promising candidate as a safe and effective vector for the delivery of heterologous antigens to prevent zoonosis and infectious disease in poultry.
单核细胞增生李斯特菌因其能够诱导强烈的细胞介导免疫反应而被用作疫苗载体。目前,减毒活单核细胞增生李斯特菌疫苗在患者中的安全性正在临床试验中进行研究。单核细胞增生李斯特菌也是一种用于家禽的有吸引力的疫苗载体;然而,该菌在家禽中的致病性和免疫原性仍有待充分阐明。在本研究中,我们在禽类感染模型中研究了一株缺失actA和plcB基因的单核细胞增生李斯特菌菌株yzuLM4ΔactA/plcB及其野生型亲本菌株yzuLM4的致病性和免疫原性。结果表明,野生型菌株可感染ISA褐壳蛋鸡,导致严重的组织破坏,包括肝脏、脾脏、心脏和肾脏出现不同程度的变性、坏死病变和炎性细胞浸润。然而,与亲本菌株相比,突变菌株在鸡胚中的毒力降低(50%致死剂量[LD(50)]高3个对数)。突变菌株在鸡中也表现出低毒力,并被宿主迅速清除。组织切片中没有明显的病理变化,但突变菌株仍保留刺激产生高水平抗溶血素O(LLO)抗体的能力。用突变菌株进行加强免疫可使通过肌肉注射途径或口服途径攻击的鸡的肝脏和脾脏中的细菌迅速清除。总体而言,我们的数据表明,野生型1/2a血清型单核细胞增生李斯特菌菌株可在鸡中引起严重疾病,但缺失actA和plcB基因的突变菌株毒力较低但诱导强烈的免疫反应。因此,这种单核细胞增生李斯特菌突变菌株是作为一种安全有效的载体来递送异源抗原以预防家禽人畜共患病和传染病的有希望的候选者。