HUMAN MONOCLONAL-ANTIBODIES AGAINST A PLETHORA OF VIRAL PATHOGENS FROM SINGLE COMBINATORIAL LIBRARIES

被引:163
作者
WILLIAMSON, RA
BURIONI, R
SANNA, PP
PARTRIDGE, LJ
BARBAS, CF
BURTON, DR
机构
[1] SCRIPPS RES INST, DEPT MOLEC BIOL, LA JOLLA, CA 92037 USA
[2] Scripps Res Inst, DEPT NEUROPHARMACOL, LA JOLLA, CA 92037 USA
[3] UNIV CATTOLICA SACRO CUORE, IST MICROBIOL, I-00168 ROME, ITALY
[4] UNIV SHEFFIELD, DEPT MOLEC BIOL & BIOTECHNOL, SHEFFIELD S10 2TN, S YORKSHIRE, ENGLAND
关键词
HUMAN ANTIBODY REPERTOIRES; PASSIVE IMMUNIZATION; OPPORTUNISTIC INFECTION; PHAGE SURFACE EXPRESSION;
D O I
10.1073/pnas.90.9.4141
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:4141 / 4145
页数:5
相关论文
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