【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 ,表明其针对甲肝病毒结构蛋白上的主要抗原决定簇更多还原

【Abstract】 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更多还原