热灭活肺炎链球菌D39X疫苗黏膜免疫小鼠可抵抗不同亚型肺炎链球菌感染  

Mucosal immunization with heat-inactivated pneumococcal vaccine D39X elicits protection against infection by different Streptococcus pneumoniae strains

作　　者：徐绣宇[1] 王一平[1] 蔡莺莺[1] 刘宇思[1] 王虹[1] 胥文春[1] 何於娟[1] 尹一兵[1] 张雪梅[1] 

机构地区：[1]重庆医科大学检验医学院临床检验诊断学教育部重点实验室,400016

出　　处：《免疫学杂志》2013年第5期395-399,共5页Immunological Journal

基　　金：国家自然科学基金(31070819);重庆市渝中区科技计划项目(20110315);实验教学管理中心创新实验项目(201117)

摘　　要：目的研制一种安全、有效且易于生产的热灭活肺炎链球菌死菌疫苗D39X,评价其作为肺炎链球菌候选疫苗的可行性。方法通过热灭活肺炎链球菌突变菌株D39X,得到无毒的死菌疫苗,鼻腔免疫Balb/c小鼠,每周1次,连续4周。末次免疫1周后,间接ELISA检测免疫小鼠特异性抗体水平;同时检测抗体亚型及细胞因子水平,并进行不同菌株攻毒的主动保护实验。结果免疫组小鼠血清中特异性IgG和唾液中特异性IgA显著升高,IgG亚型主要为IgG1和IgG2b;免疫小鼠脾细胞特异性分泌IL-4和IL-17A;19F型肺炎链球菌在免疫小鼠中的载量显著低于对照组小鼠;灭活D39X黏膜免疫可有效延长肺炎链球菌D39、6B型和3型感染小鼠的生存时间;被动免疫也具有保护作用。结论热灭活的D39X黏膜免疫可诱导小鼠产生体液免疫和细胞免疫反应,有效抵抗不同血清型肺炎链球菌的感染,是一种有开发前景的肺炎链球菌疫苗。In previous research, our group found a new pneumococcal strain with capsule-deficient mutant, D39X, and demonstrated its ability to elicit broad serotype independent protection against pneumococcal infection. Here, Balb/c mice were intranasally immunized with heat-inactivated D39X plus cholera toxin adjuvant for four times. Then, D39X specific humoral and cellular immune responses were determined and protection was evaluated in pneumococcal colonization model as well as lethal pneumococcal infection model. Our results showed that inactivated D39X induced powerful humoral and Th2/Th17 cellular immune responses. And the bacterial loads of strain 19F in immune mice were significantly lower than that in control mice. Mucosal immunization with heat inactivated D39X plus CT could prolong the survival time of mice infected with pneumococcal D39, serotype 6B and type 3, respectively. In conclusion, heat inactivated pneumococcal whole cell vaccine D39X is a potentially safe and less complex vaccine that may offer broad protection against S. pneumoniae.

关 键 词：热灭活 肺炎链球菌 黏膜免疫 保护 

分 类 号：R392[医药卫生—免疫学]