重组轮状病毒抗原表位亚单位疫苗的小鼠保护性  

Protective Efficacy of Recombinant Rotavirus Epitope-based Vaccine in Mice

作　　者：刘晓[1] 李嘉琦[1] 熊新宇[1] 陈瑜娜[1] 彭梅[1] 代青[1] 文喻玲[1] 陈元鼎[1] 

机构地区：[1]中国医学科学院中国协和医科大学医学生物学研究所中心实验室,昆明650118

出　　处：《中国医学科学院学报》2005年第2期216-222,共7页Acta Academiae Medicinae Sinicae

基　　金：云南省自然科学基金(2001C0073M)~~

摘　　要：目的评价重组表达的轮状病毒(R V)抗原表位疫苗的小鼠体内保护效果及安全性。方法在以FlockH ouse virus病毒外壳蛋白为载体的外源抗原表位呈递系统(FH V-R NA2系统)中构建和重组表达R V V p4蛋白上第223～262位抗原表位(R EA BC)在原核系统犤;质粒pET,大肠杆菌BL21(D E3)犦中表达的REABC免疫小鼠用细胞培养适应的参照RV W a(G1PA型)和SA11(G3P2型)经口腔灌胃攻击,对R V攻击后的免疫小鼠和对照小鼠的感染症状、排毒情况、血清抗体中和病毒感染性效价进行测定和分析。结果R EA BC可诱导免疫小鼠产生较强的抗-W a和抗-SA11株血清中和抗体和特异的免疫记忆反应,有效保护免疫小鼠对W a和SA11的攻击(不腹泻),减少病毒在体内复制水平和排毒时间,与对照组相比差异具有显著性(P<0.001)。结论重组表达RV抗原表位REABC对小鼠具有较好的免疫保护效果和安全性。Objective To evaluate in vivo immunological protective efficacy and safety of expressed recombinant rotavirus epitopes in mice. Methods Using the Flock House virus capsid protein as a vector, three epitopes derived from rotavirus Vp4 amino acid 223-242rotavirus epitope A,(REA), 243-262rotavirus epitope B,(REB), and 234-251rotavirus epitope C,(REC)were genetically engineered on the surface of the vector protein and expressed in pET-3(E. coli BL21DE3)system into multiple epitopes, REABC, which comprises REA, REB, and REC. Kunming strain mice were inoculated with the recombinant epitopes REABC, and then challenged perorally by cell culture-adapted rotavirus Wa(type G1P1A)and SA11(type G3P2). Infection syndrome was observed, and virus antigen in stools of mice and serum neutralizing antibody activities were determined and analyzed. Results The recombinant epitopes REABC significantly induced rotavirus specific neutralyzing antibodies against WA and SA11, reduced virus reproduction, elicitted immune memory in inoculated mice, and protected inoculated mice from challenge by WA or SA11(P < 0.001). Conclusion The recombinant epitopes have high immuno-logical protective efficacy and mild side effects in mice. It may be used as an epitope-based vaccine candidate in human.

关 键 词：轮状病毒 重组抗原表位亚单位疫苗 免疫保护性 

分 类 号：R373.2[医药卫生—病原生物学] R392.11[医药卫生—基础医学]