title: Importance of inhibition of binding of complement factor H for serum bactericidal antibody responses to meningococcal factor H-binding protein vaccines.
abstract: BACKGROUND
  Factor H (fH) binding protein (fHbp) is part of vaccines developed for prevention of meningococcal serogroup B disease. More than 610 fHbp amino acid sequence variants have been identified, which can be classified into 2 subfamilies. The extent of cross-protection within a subfamily has been difficult to assess because of strain variation in fHbp expression.
  
  
  METHODS
  Using isogenic mutant strains, we compared cross-protective serum antibody responses of mice immunized with 7 divergent fHbp variants in subfamily B, including identification numbers (ID) 1 and 55, which were chosen for vaccine development.
  
  
  CONCLUSIONS
  In the presence of the human complement downregulator fH, the ability of the anti-fHbp antibodies to deposit sufficient complement C3b on the bacterial surface to elicit bactericidal activity required inhibition of binding of fH by the anti-fHbp antibodies. With less bound fH, the bacteria became more susceptible to complement-mediated bactericidal activity. Among the different fHbp sequence variants, those more central in a phylogenic network than ID 1 or 55 elicited anti-fHbp antibodies with broader inhibition of fH binding and broader bactericidal activity. Thus, the more central variants show promise of extending protection to strains with divergent fHbp sequences that are covered poorly by fHbp variants in clinical development.
authors.affiliation: Center for Immunobiology and Vaccine Development, Children's Hospital Oakland Research Institute, California, USA.
authors.forename: Monica
authors.initials: M
authors.lastname: Konar
authors.forename: Dan M
authors.initials: DM
authors.lastname: Granoff
authors.forename: Peter T
authors.initials: PT
authors.lastname: Beernink
mesh_terms: D000328:Adult; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood*; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D001770:Blood Bactericidal Activity; D017242:Complement Factor H / Q000276:immunology* / Q000378:metabolism*; D003165:Complement System Proteins / Q000276:immunology; D056738:Cross Protection; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008589:Meningococcal Infections / Q000276:immunology / Q000517:prevention & control; D022401:Meningococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D050296:Microbial Viability
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D022401:Meningococcal Vaccines; C484699:factor H-binding protein, Neisseria meningitidis; D017242:Complement Factor H; D003165:Complement System Proteins
keywords: LP2086; Neisseria meningitidis; bactericidal antibody; complement activation; fHbp; phylogeny; vaccine