以Pam2CSK4为佐剂的减毒活疫苗D39△CPS-TA可保护幼鼠抵抗肺炎链球菌感染  

A live attenuated vaccine D39△CPS-TA with Pam2CSK4 as adjuvant elicits protection against pneumococcal infection in infant mice

作　　者：曾令斌[1] 廖璞[2] 宋志新[1] 赵家宁[1] 高松[1] 吴盈盈[1] 尹一兵[1] 胥文春[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,重庆400016 [2]重庆市第三人民医院检验科,重庆400014

出　　处：《第三军医大学学报》2014年第16期1651-1655,共5页Journal of Third Military Medical University

基　　金：国家自然科学基金(31070819;31270984);重庆市科委重点实验室专项经费(CSTC);重庆市教委课题(KJ120318)~~

摘　　要：目的评价新型减毒肺炎链球菌疫苗株D39△CPS-TA与佐剂Pam2CSK4联用时在幼鼠模型中的免疫保护效果及安全性。方法 D39△CPS-TA、D39△CPS-TA+霍乱毒素(cholera toxin,CT)、D39△CPS-TA+Pam2CSK4经鼻免疫C57/BL6幼鼠,每周1次,共4次。末次免疫后1周,酶联免疫吸附法(ELISA)测定抗体及细胞因子水平。末次免疫后2周,采用19F型和2型肺炎链球菌攻毒,观察免疫保护效果。生存率实验评价D39△CPS-TA的安全性;从体质量变化和肺组织病理学改变2个角度,评价Pam2CSK4的安全性。结果 D39△CPS-TA+Pam2CSK4免疫幼鼠可有效引起抗原特异性IgG升高,其中以IgG1为主;能有效促进IFN-γ、IL-4、IL-10和IL-17A水平升高;能有效抵抗19F型肺炎链球菌在小鼠鼻咽部定植;能有效提高小鼠经2型肺炎链球菌攻毒后的生存率。高剂量D39△CPS-TA可被幼鼠耐受,Pam2CSK4较CT安全。结论 D39△CPS-TA+Pam2CSK4经鼻免疫幼鼠可安全有效地刺激其体液免疫和细胞免疫,进而对抗肺炎链球菌感染。Objective To evaluate the safety and efficacy of a novel pneumococcal attenuated vaccine strain D39△CPS-TA when delivered intra-nasally with adjuvant Pam2CSK4 in a infant mice model of pneumococcal infection. Methods C57/BL6 infant mice were intra-nasally administrated on days 0, 7, 14 and 28 with 1 dose of D39△CPS-TA＋ cholera toxin （CT） or Pam2CSK4, with D39△CPS-TA alone or with one of selected adjuvant alone. In 1 week after the last immunization, antibodies and cytokines levels were measured by enzyme-linked immunosorbent assay （ELISA）. In 2 weeks after the last immunization, mice were challenged with pneumococcal serotype 19F or 2 and protective effects were observed. Furthermore, the safety of D39△CPS-TA was measured by a survival experiment and the safety of Pam2CSK4 was evaluated by monitoring body weight and pathological analysis. Results Intranasal immunization with D39△CPS-TA＋Pam2CSK4 in infant mice induced IgG1-based rise in antigen-specific IgG, increase of IFN-γ, IL-4, IL-10 and IL-17A, clearance of nasal colonization of pneumococcal serotype 19F and protective effects against lethal infection of pneumococcal serotype 2. High dose of D39△CPS-TA was tolerated by infant mice and Pam2CSK4 was safer than CT. Conclusion Intra-nasal immunization with D39△CPS-TA＋Pam2CSK4 in infant mice stimulates humeral and cellular immune responses safely and effectively, and protects mice against pneumococcal infection.

关 键 词：肺炎链球菌 疫苗 佐剂 安全性 

分 类 号：R378.14[医药卫生—病原生物学] R392.12[医药卫生—基础医学]