人源中和性抗甲型肝炎病毒抗体Fab段基因的序列分析及可溶性表达  

Sequence Analysis and Gene Expression of Neutralizing Recombinant Human Fab Antibody Fragments to Hepatitis A Virus

作　　者：曹经瑗[1] 梁米芳[1] 郭可謇[1] 孟庆玲[1] 纪燕 詹美云[1] 

机构地区：[1]中国预防医学科学院病毒学研究所,北京100052

出　　处：《病毒学报》2001年第3期221-224,共4页Chinese Journal of Virology

基　　金：国家自然科学基金资助 (3 970 0 12 3 )

摘　　要：在用噬菌体表面呈现系统获得人源抗甲型肝炎 (甲肝 )病毒中和性基因工程Fab抗体的基础上 ,对所获得的 4株中和性Fab抗体轻重链可变区基因进行了序列分析、可溶性表达及生物学特性鉴定。 4株Fab抗体重链可变区拥有 99%同源的核苷酸序列和相同的CDR区氨基酸序列 ,属于VHⅢ基因家族。而轻链可变区核苷酸序列同源性为 95 %和相似的CDR区氨基酸序列 ,属于VL5基因家族。这些重组抗体都能与人甲肝恢复期血清及具有中和活性的鼠抗甲肝单克隆抗体产生竞争抑制反应 。The human derived neutralizing recombinant Fab antibodies to hepatitis A virus(HAV)developed by using phage display technology have been previously reported In this report,the variable region genes of the heavy and light chains of the four human Fab antibodies to HAV were sequenced and analyzed The deduced amino acid sequence in VH CDR region of all four Fab antibodies were identical and belong to VHⅢ gene family,while the VL region of the light chain genes showed a rare difference in CDR regions,and all belong to VL5 gene family Soluble Fab antibodies were expressed in bacteria and showed complete competition with patient's convalescent serum as well as one mouse neutralizing McAb which recognized major protein of HAV,indicating that the recombinant human Fab antibodies recognize the dominant epitopes of HAV that induce major immune response in human during HAV infection These human Fab fragments will be further linked to human IgG Fc portion and will be more promising for prophylaxis of HAV infection in the future

关 键 词：重组Fab抗体 甲肝病毒 序列分析 可溶性表达 人源中和抗体 

分 类 号：R373.21[医药卫生—病原生物学] R392.2[医药卫生—基础医学]