Analysis of the epitope and neutralizing capacity of human monoclonal antibodies induced by hepatitis B vaccine
Analysis of the epitope and neutralizing capacity of human monoclonal antibodies induced by hepatitis B vaccine
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DOI：
10.1016/j.antiviral.2010.04.006
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发表时间：
2010-07-01
影响因子：
7.6
通讯作者：
Muraguchi, Atsushi
中科院分区：
文献类型：
--
作者：
Tajiri, Kazuto;Ozawa, Tatsuhiko;Muraguchi, Atsushi
乙肝病毒是一种重要的世界性公共卫生问题的感染性病原体。然而，疫苗诱导的抗体预防乙肝病毒感染的机制尚不清楚。为了探讨乙肝表面抗原(HBs-Ag)免疫诱导的抗体预防乙肝病毒感染的机制，我们用一种新型的细胞微阵列系统从接种者的外周血B淋巴细胞中制备了抗-HBs的人源单抗。然后我们鉴定了H/L链的免疫球蛋白亚类、L链亚型和V基因谱系，以及这些单抗的亲和力。我们还用人工合成的多肽确定了单抗的表位，并用肝细胞系HepaRG测定了单抗的中和乙肝病毒活性。因此，主要以IgG1和kappa链作为抗-HBs的单抗。70%的单抗与小乙肝表面抗原的环区结合，表现出较强的中和活性。它们的亲和力与中和活性之间没有关系。在HepaRG细胞系实验中，识别第一环结构域的单抗组合显示出协同作用，其中和活性超过传统的乙肝免疫球蛋白(HBIG)。这些结果可能有助于开发有效的单抗治疗，以取代传统的HBIG治疗。(C)2010爱思唯尔B.V.保留所有权利。
Hepatitis B virus (HBV) is an infectious agent that is a significant worldwide public health issue. However, the mechanism by which vaccination-induced antibodies prevent HBV infection remains unclear. To investigate the mechanism by which antibodies induced by hepatitis B surface Ag (HBsAg)-vaccination prevent HBV infection in humans, we prepared human monoclonal antibodies (mAbs) against HBsAg using a novel cell-microarray system from peripheral blood B-lymphocytes from vaccinated individuals. We then characterized the IgG subclass, L-chain subtype, and V-gene repertoire of the H/L-chain, as well as affinities of each of these mAbs. We also determined the epitopes of the individual mAbs using synthesized peptides, and the HBV-neutralizing activities of mAbs using the hepatocyte cell line HepaRG. Consequently, IgG1 and kappa chain was mainly used as the mAbs for HBsAg. Seventy percent of the mAbs bound to the loop domain of the small-HBsAg and showed greater neutralizing activities. There were no relationships between their affinities and neutralization activities. A combination of mAbs recognizing the first loop domain showed a synergistic effect on HBV-neutralizing activity that surpassed conventional hepatitis B-Ig (HBIG) in the HepaRG cell line assay. These results may contribute to the development of effective mAb treatment against HBV infection replacing conventional HBIG administration. (C) 2010 Elsevier B.V. All rights reserved.