肠毒素大肠杆菌攻毒小鼠模型的建立以及疫苗候选株保护效果的评价  

Establishment of mice models following intranasal challenge with enterotoxigenic Escherichia coli strains and evaluation of protective effect following intranasal immunization with vaccine candidates

作　　者：王志斌[1] 姜普林[1] 曾年华[1] 李淑琴[2] 王令春[2] 李燕[3] 熊仕秋[3] 张兆山[2] 

机构地区：[1]广州军区疾病预防控制中心,广东省广州市510507 [2]北京生物工程研究所,北京市100071 [3]中山大学基础医学院,广东省广州市510089

出　　处：《世界华人消化杂志》2006年第28期2753-2758,共6页World Chinese Journal of Digestology

基　　金：国家高技术研究发展计划资助项目(863计划);No.2004AA215212~~

摘　　要：目的:建立肠毒素大肠杆菌攻毒小鼠模型以及应用模型对疫苗候选株免疫效果进行评价．方法:通过鼻饲半数致死量(LD50)肠毒素大肠杆菌E44813,E44815和E11881A观察小鼠肺病理学变化、肺部细菌清除情况变化,建立肠毒素大肠杆菌鼻饲小鼠模型;应用鼻饲小鼠模型观察疫苗候选株FE1,FE3,FE6保护效果．结果:鼻饲LD50剂量肠毒素大肠杆菌小鼠的病理特征是肺组织存在大量的淋巴细胞、巨噬细胞、中性粒细胞和浆细胞,为多病灶支气管肺炎,肺部细菌清除缓慢,至第7天仍能检测到105数量级的细菌．应用疫苗候选株免疫后进行攻毒,小鼠没有发病和死亡,病理特征主要是淋巴细胞少量增多,肺部细菌清除迅速,至第7天已检测不到细菌,与对照有显著性差异(0 CFU／g vs 6．2×105,5．4×105,2．3×105 CFU／g,P<0．05)．结论:肠毒素大肠杆菌鼻饲小鼠模型能够为疫苗筛选和评价提供了有效途径,同时也证实了疫苗候选株FE1,FE3,FE6具有良好的免疫保护效果．AIM： To establish the mice models following intranasal challenge with enterotoxigenic Escherichia coli （ETEC） strains E44813, E44815, E11881A, and evaluate the immune effect of vaccine candidates FE1, FE3, FE6 following intranasal immunization. METHODS： The histopathological response in the lungs and the clearance of ETEC from the lungs was measured following intranasal challenge of BALB/c mice with LD50-dose ETEC strains E44813, E44815 and E11881A. The protective effect of vaccine candidates FE1, FE3 and FE6 were evaluated using the established models. RESULTS： A large quantity of lymphocytes, macrophages, neutrophils, and plasma cells were found in the lungs of mice. Multifocal bronchopneumonia was the main pathological feature under microscope following intranasal challenge with ETEC strains E44813, E44815, and E11881A. The bacteria were cleared from the lungs of the mice at a slow rate over 1-wk period and till the 7^th day, bacteria at 105 levels were still detected. After high titers of antibodies were detected in mice intranasally immunized with vaccine candidates FE1, FE3, and FE6, the mice were challenged by LD50-dose E44813, E44815, and E11881A intranasally. No deaths occurred, and low numbers of lymphocytes were the main pathological feature. The bacteria were rapidly cleared from the lungs of the mice over 1-wk period, and no bacteria were detected at the 7^th day. The numbers of the bacteria were significantly different between the experimental group and control group （0 CFU/g vs 6.2×10^5, 5.4×10^5, 2.3×10^5 CFU/g, P 〈 0.05）. CONCLUSION： Intranasal challenge of Balb/ c mice with ETEC strains may provide a useful method to evaluate the vaccine. This study also demonstrates that the vaccine candidate FE1, FE3 and FE6 have good protective effect.

关 键 词：肠毒素大肠杆菌 攻毒实验 小鼠模型 疫苗菌株 保护效果 

分 类 号：R-332[医药卫生] R392