Human monoclonal Fab fragments derived from a combinatorial library bind to respiratory syncytial virus F glycoprotein and neutralize infectivity.
Respiratory syncytial virus (RSV) is the most important cause, throughout the world, of severe viral lower respiratory tract illness in young children. Antibodies are known to mediate resistance to RSV infection and illness. We have isolated a number of human monoclonal Fab fragments to RSV F glycoprotein from a combinatorial antibody library expressed on the surface of phage. One of these neutralized a wide range of virus isolates, 10 subgroup A and 9 subgroup B isolates, with a titer (60% neutralization) of approximately 0.1-1.0 micrograms/ml. Another Fab neutralized diverse isolates at a concentration somewhat higher. These human Fab fragments show great promise for use in the prophylaxis or therapy of serious RSV lower respiratory tract disease. For intramuscular or intravenous administration, whole antibodies will be required, whereas for aerosol application, F(ab')2 or Fab fragments may suffice.
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000235:genetics* / Q000378:metabolism*; D000956:Antigens, Viral / Q000276:immunology*; D001483:Base Sequence; D001666:Binding Sites, Antibody; D001667:Binding, Competitive; D004797:Enzyme-Linked Immunosorbent Assay; D015723:Gene Library; D006679:HIV Seropositivity / Q000276:immunology; D015707:HN Protein; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000235:genetics* / Q000378:metabolism*; D007135:Immunoglobulin Variable Region / Q000235:genetics* / Q000378:metabolism*; D008214:Lymphocytes / Q000276:immunology; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D009838:Oligodeoxyribonucleotides; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins / Q000276:immunology*; D014764:Viral Proteins
D000911:Antibodies, Monoclonal; D000956:Antigens, Viral; D015707:HN Protein; D007140:Immunoglobulin Fab Fragments; D007135:Immunoglobulin Variable Region; D009838:Oligodeoxyribonucleotides; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins; D014764:Viral Proteins; C116204:attachment protein G; D012313:RNA