Human monoclonal antibodies against a plethora of viral pathogens from single combinatorial libraries.
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.
Williamson
R A
RA
Department of Immunology, Scripps Research Institute, La Jolla, CA 92037.
Burioni
R
R
Sanna
P P
PP
Partridge
L J
LJ
Barbas
C F
CF
Burton
D R
DR
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics; D000914:Antibodies, Viral / Q000097:blood* / Q000235:genetics*; D000918:Antibody Specificity; D001483:Base Sequence; D001853:Bone Marrow / Q000276:immunology; D002460:Cell Line; D003587:Cytomegalovirus / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D015723:Gene Library; D015497:HIV-1 / Q000276:immunology; D014645:Herpesvirus 3, Human / Q000235:genetics; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000097:blood* / Q000235:genetics*; D008214:Lymphocytes / Q000276:immunology; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction / Q000379:methods; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012136:Respiratory Syncytial Viruses / Q000276:immunology; D015183:Restriction Mapping; D012412:Rubella virus / Q000276:immunology; D017386:Sequence Homology, Amino Acid; D018139:Simplexvirus / Q000276:immunology; D014780:Viruses / Q000276:immunology* / Q000472:pathogenicity
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D007143:Immunoglobulin Heavy Chains; D009838:Oligodeoxyribonucleotides; D012313:RNA