title: Generation and epitope mapping of a sub-group cross-reactive anti-respiratory syncytial virus G glycoprotein monoclonal antibody which is protective in vivo.
abstract: Passively administered antibodies to conserved epitopes on the attachment (G) glycoprotein of human respiratory syncytial virus (hRSV) have potential in the immunoprophylaxis of human infections. This study set out to generate monoclonal antibodies (MAbs) recognizing all prevalent lineages of HRSV and capable of immunoprophylaxis in mice. Two murine MAbs of broad specificity for prevalent virus strains were generated by immunization of mice with hRSV of sub-group A followed by selection of hybridomas on recombinant G glycoprotein from a sub-group B virus. The anti-G hybridomas generated secreted antibody of high affinity but negligible neutralizing capacity one of which was tested in mice and found to be protective against live virus challenge. Western blotting and partial epitope mapping on transiently expressed G-glycoprotein fragments indicate that these antibodies recognize a complex epitope on the protein backbone of the molecule involving residues both C'- and N-terminal to the central conserved motif.
authors.affiliation: Institute of Cellular Medicine, The Medical School, Newcastle upon Tyne, United Kingdom.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Robinson
authors.forename: Cheng-Siang
authors.initials: CS
authors.lastname: Tan
authors.forename: Fiona
authors.initials: F
authors.lastname: Fenwick
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Chambers
authors.forename: Edward G
authors.initials: EG
authors.lastname: Routledge
authors.forename: Geoffrey L
authors.initials: GL
authors.lastname: Toms
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000302:isolation & purification* / Q000627:therapeutic use; D000914:Antibodies, Viral / Q000276:immunology / Q000302:isolation & purification / Q000627:therapeutic use; D004195:Disease Models, Animal; D018604:Epitope Mapping; D005260:Female; D008807:Mice, Inbred BALB C; D018357:Respiratory Syncytial Virus Infections / Q000517:prevention & control*; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology*; D016896:Treatment Outcome; D014760:Viral Fusion Proteins / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; C502275:G glycoprotein, Respiratory syncytial virus; D014760:Viral Fusion Proteins
keywords: conserved epitope; epitope mapping; hybridoma; immunoprophylaxis