Human monoclonal antibodies against a plethora of viral pathogens from single combinatorial libraries

Proc Natl Acad Sci U S A. 1993 May 1;90(9):4141-5. doi: 10.1073/pnas.90.9.4141.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal / genetics
  • Antibodies, Viral / blood*
  • Antibodies, Viral / genetics*
  • Antibody Specificity
  • Base Sequence
  • Bone Marrow / immunology
  • Cell Line
  • Cytomegalovirus / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Fluorescent Antibody Technique
  • Gene Library
  • HIV-1 / immunology
  • Herpesvirus 3, Human / genetics
  • Humans
  • Immunoglobulin Heavy Chains / blood*
  • Immunoglobulin Heavy Chains / genetics*
  • Lymphocytes / immunology
  • Molecular Sequence Data
  • Oligodeoxyribonucleotides
  • Polymerase Chain Reaction / methods
  • RNA / genetics
  • RNA / isolation & purification
  • Respiratory Syncytial Viruses / immunology
  • Restriction Mapping
  • Rubella virus / immunology
  • Sequence Homology, Amino Acid
  • Simplexvirus / immunology
  • Viruses / immunology*
  • Viruses / pathogenicity

Substances

  • Antibodies, Monoclonal
  • Antibodies, Viral
  • Immunoglobulin Heavy Chains
  • Oligodeoxyribonucleotides
  • RNA