title: A broadly cross-reactive monoclonal antibody against an epitope on the n-terminus of meningococcal fHbp.
abstract: Meningococcal factor H binding protein (fHbp) is an important vaccine antigen for prevention of disease caused by capsular group B strains. The protein has been sub-classified into three variant groups. Most anti-fHbp antibodies are variant group-specific and recognize epitopes on the C-terminal domain. We report a murine IgG1 mAb, JAR 41, which broadly cross-reacted with fHbp sequence variants from all variant groups. The mAb bound to the surface of live meningococci with fHbp from each of the three variant groups. In combination with second non-bactericidal anti-fHbp mAbs, JAR 41 elicited complement-mediated bactericidal activity in vitro, and augmented passive protection against meningococcal bacteremia in human fH transgenic rats. The epitope was located on a conserved region of the N-terminal portion of the fHbp molecule opposite that of fH contact residues. The data underscore the importance of broadly cross-reactive, surface-exposed epitopes on the N-terminal domain in the design of protective fHbp vaccines.
authors.affiliation: Children's Hospital Oakland Research Institute , Oakland, CA 94609,  U.S.A.
authors.forename: David M
authors.initials: DM
authors.lastname: Vu
authors.forename: Rolando
authors.initials: R
authors.lastname: Pajon
authors.forename: Donald C
authors.initials: DC
authors.lastname: Reason
authors.forename: Dan M
authors.initials: DM
authors.lastname: Granoff
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology*; D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology*; D001426:Bacterial Proteins / Q000737:chemistry / Q000276:immunology*; D003165:Complement System Proteins / Q000502:physiology; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans
chemical_list: D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D000939:Epitopes; C484699:factor H-binding protein, Neisseria meningitidis; D003165:Complement System Proteins