HCV多表位抗原基因重组减毒口服活菌苗的研究  

IMMUNE RESPONSES OF A RECOMBINED LIVE SALMONELLA TYPHIMURIUM SL3261 EXPRESSING A MULTI-EPITOPE ANTIGEN OF HCV

作　　者：黄建生[1] 解咏梅[1] 张潜[1] 沈先荣 任大明[1] 吉冬梅 许谆 贾福星[2] 雷呈祥[2] 兰和魁[3] 郑维扬[3] 张丽芸[3] 陈立茵[3] 郭明秋[3] 

机构地区：[1]复旦大学生命科学院,上海200433 [2]海军医学研究所,上海200433 [3]第一军医大学,广州510515

出　　处：《微生物学报》2000年第5期495-499,共5页Acta Microbiologica Sinica

基　　金：国家自然科学基金资助!( 3 9780 0 0 2 )&&

摘　　要：把丙型肝炎病毒 (hepatitisCvirus,HCV)复合多表位抗原基因PCX与 β 半乳糖苷酶基因 (GZ)融合后 ,构建重组减毒鼠伤寒沙门氏菌口服活菌苗SL32 61 ( pWR/PCX) ,免疫小鼠及家兔后 ,于第 6周始可检测到低水平的抗 GZ PCXIgG( 1∶2 0 0 ) ,至 3月时最高滴度分别达1∶80 0及 1∶2 560 0 ,均显著高于宿主菌SL32 61组及空白对照组。在免疫小鼠的肠道灌洗液中可检测到抗 GZ PCXsIgA。GZ PCX抗原可促进免疫小鼠及家兔淋巴细胞增殖 ,诱发明显的迟发性超敏反应 (DTH)。口服免疫后小鼠体重出现一过性下降 ,但未见其它明显的毒性作用 ,安全性较好。本研究从新的角度探讨了HCV复合多表位重组口服活菌苗的可行性 ,为HCV疫苗的研究提供新的实验依据。A multi\|epitope antigen gene of hepatitis C virus(HCV) was fused to β galactosidase gene and introduced into attenuated \%Salmonella typhimurium\% SL3261 to construct HCV recombined live vaccine candidate SL3261 (pWR/PCX). When the oral live bacteria were used to immunize mice or rabbits, specific anti\|GZ\|PCX IgG was detected at week 6 and the strongest antibody responses happened at week 12 at a titer of 1∶800 and 1∶\{25 600\} in mice and rabbits, respectively, which showed significant difference compared with those of SL3261 and blank controls. Anti\|GZ\|PCX sIgA in mice's intestine and anti\|LPS antibody in sera were also detected. The oral live bacteria elicited obvious DTH reaction and proliferation response of peripheral lymphocytes by GZ\|PCX antigen. The body weight of immunized mice slightly decreased but no other toxic effects was observed, which showed the safety of oral immunization. The study of oral live HCV multi\|epitope vaccine might be able to provide a new route for the researches of HCV vaccines.

关 键 词：丙型肝炎 口服活菌苗 多表位抗原 免疫应答 

分 类 号：Q939.91[生物学—微生物学]