HUMAN MONOCLONAL-ANTIBODIES AGAINST A PLETHORA OF VIRAL PATHOGENS FROM SINGLE COMBINATORIAL LIBRARIES
HUMAN MONOCLONAL-ANTIBODIES AGAINST A PLETHORA OF VIRAL PATHOGENS FROM SINGLE COMBINATORIAL LIBRARIES
复制标题
DOI：
10.1073/pnas.90.9.4141
复制
发表时间：
1993-05-01
影响因子：
11.1
通讯作者：
BURTON, DR
中科院分区：
文献类型：
--
作者：
WILLIAMSON, RA;BURIONI, R;BURTON, DR
常规的抗体产生通常需要在制备程序之前立即用抗原进行主动免疫。组合抗体库技术提供了在单个时间点克隆一系列抗体特异性，然后随意访问这些特异性的可能性。在这里，我们表明，人单克隆抗体Fab片段对过多的传染性病原体可以很容易地从一个单一的库。对许多文库的进一步检查表明，只要在供体的血清中可以检测到针对病原体的抗体，则可以从相应的文库中获得特异性抗体。我们描述了一代人的Fab片段对单纯疱疹病毒1型和2型，人巨细胞病毒，水痘带状疱疹病毒，风疹，人类免疫缺陷病毒1型，呼吸道合胞病毒。这些抗体显示出高度特异性，并且许多抗体在体外有效中和病毒。
Conventional antibody generation usually requires active immunization with antigen immediately prior to the preparation procedure. Combinatorial antibody library technology offers the possibility of cloning a range of antibody specificities at a single point in time and then accessing these specificities at will. Here we show that human monoclonal antibody Fab fragments against a plethora of infectious agents can be readily derived from a single library. Further examination of a number of libraries shows that whenever antibody against a pathogen can be detected in the serum of the donor, then specific antibodies can be derived from the corresponding library. We describe the generation of human Fab fragments against herpes simplex virus types 1 and 2, human cytomegalovirus, varicella zoster virus, rubella, human immunodeficiency virus type 1, and respiratory syncytial virus. The antibodies are shown to be highly specific and a number are effective in neutralizing virus in vitro.