CpG寡核苷酸可作为幽门螺杆菌疫苗的佐剂  

CpG-Oligodeoxynucleotide is the ideal adjuvant for development of a Helicobacter pylori vaccine

作　　者：史彤[1] 刘文忠[1] 萧树东[1] 

机构地区：[1]上海第二医科大学附属仁济医院上海市消化疾病研究所,200001

出　　处：《中华消化杂志》2003年第4期233-236,共4页Chinese Journal of Digestion

基　　金：上海市重点学科建设项目资助

摘　　要：目的　研究一种新型黏膜佐剂 (一段寡核苷酸 ,序列为 :非甲基化的 5′ …嘌呤 嘌呤 CpG 嘧啶 嘧啶 … 3′(CpG ODN)是否可作为幽门螺杆菌 (Hp)疫苗的佐剂成分。 方法　C5 7BL/6小鼠经口灌胃给予Hp整菌超声粉碎物 (WCS) /CpG ODN或WCS/霍乱毒素 (CT) ,或经鼻给予WCS/CpG ODN ,并设立相应对照组。免疫程序及途径为每周 1次 ,共 4次 ,最后 1次免疫后 1周 ,以 5× 10 8Hp活菌攻击小鼠 ,攻击后 2周和 8周时 ,处死小鼠 ,鉴定Hp感染情况。同时收集小鼠血清、唾液、胃液 ,ELISA法检测血清中IgG、IgG1、IgG2a及IgA水平和唾液、胃液中IgA水平。 结果　以WCS作为抗原 ,不同佐剂及接种途径免疫小鼠 ,保护率分别为 :口服CT组 75 % (9/12 ) ,口服CpG ODN组 0 % (0 /10 ) ,滴鼻CpG ODN组 70 % (7/10 )。第 2和第 8周滴鼻CpG ODN组小鼠血清IgG2a水平显著高于未免疫的对照组(P <0 .0 5 )。结论　通过鼻道免疫CpG ODN是一很有前景的Hp疫苗佐剂成分。Objective To investigate whether a novel mucosal adjuvant (DNA containing six base pair motifs consisting of an unmethylated CpG dinucleotide flanked by two 5′ purines and two 3′ pyrimidines, CpG Oligodeoxynucleotide, CpG ODN),which has not been shown to have significant toxicity,could be an ideal mucosal adjuvant for the development of a H. pylori vaccine in mice model. Methods C57BL/6 mice were orally or intranasally immunized with H. pylori whole cell sonicate(WCS) / cholera toxin (CT) or WCS /CpG ODN, and the corresponding control groups were set. Mice were dosed once a week for four weeks. One week after the last immunization, all animals were challenged by live H. pylori (5×10 8) three times in a five day duration. Two and 8 weeks after the last challenge, all animals were sacrificed to examine infection of H. pylori. Sera, saliva, gastric juice were collected to measure the concentrations of IgG, IgG1, IgG2a and IgA by ELISA. Results The protecting rates against H. pylori infection were 75%(9/12), 70% (7/10) and 0 (0/10) in the group of WCS/CT orally, WCS/CpG ODN intranasally and WCS/CpG ODN orally, respectively. Significantly higher levels of serum IgG2a antibody was found in the group immunized with WCS plus CpG ODN than those found in the sham immunized controls ( P <0.05) both at 2 and 8 week. Conclusion CpG ODN given intranasally is the ideal adjuvant for development of a H. pylori vaccine.

关 键 词：幽门螺杆菌 疫苗 佐剂 CPG寡核苷酸 鼻道免疫 

分 类 号：R392[医药卫生—免疫学]