title: Antibodies recognizing a variety of different structural motifs on meningococcal Lip antigen fail to demonstrate bactericidal activity.
abstract: The neisserial Lip antigen is a conserved antigen associated with the pathogenic Neisseria species, and is composed of multiple repeats of a consensus pentapeptide. A series of monoclonal antibodies reacting with meningococcal Lip antigen were subjected to epitope mapping, using solid-phase synthetic peptides based on the consensus repeat sequence. The antibodies were found to recognize different continuous epitopes based on the consensus sequence. One monoclonal antibody was utilized in affinity chromatography to obtain purified Lip antigen and the antigen was used for immunization of mice. The resulting antisera did not recognize Lip antigen on Western blots but reacted specifically with Lip antigen in immune precipitation experiments, indicating that the predominant polyclonal immune response was directed against conformational epitopes. Despite the diversity of both continuous and conformational epitopes recognized by the antibodies produced, none of the antibodies demonstrated the ability to promote complement-mediated bactericidal activity. Thus despite its initial apparent promise as a potential vaccine candidate the case for the inclusion of Lip antigen in vaccine formulation cannot be supported at present.
mesh_terms: D000595:Amino Acid Sequence; D000907:Antibodies, Bacterial / Q000276:immunology* / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology* / Q000302:isolation & purification; D001433:Bacteriolysis / Q000187:drug effects; D003165:Complement System Proteins / Q000494:pharmacology; D000939:Epitopes / Q000276:immunology*; D008969:Molecular Sequence Data; D009345:Neisseria meningitidis / Q000187:drug effects / Q000276:immunology*; D009842:Oligopeptides / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D000939:Epitopes; C079135:Lip antigen; D009842:Oligopeptides; D003165:Complement System Proteins