title: Binding of Complement Factor H (FH) Decreases Protective Anti-FH Binding Protein Antibody Responses of Infant Rhesus Macaques Immunized With a Meningococcal Serogroup B Vaccine.
abstract: BACKGROUND
  The meningococcal vaccine antigen, factor H (FH)-binding protein (FHbp), binds human complement FH. In human FH transgenic mice, binding decreased protective antibody responses.
  
  
  METHODS
  To investigate the effect of primate FH binding, we immunized rhesus macaques with a 4-component serogroup B vaccine (4CMenB). Serum FH in 6 animals bound strongly to FHbp (FHbp-FH(high)) and, in 6 animals, bound weakly to FHbp (FHbp-FH(low)).
  
  
  RESULTS
  There were no significant differences between the respective serum bactericidal responses of the 2 groups against meningococcal strains susceptible to antibody to the NadA or PorA vaccine antigens. In contrast, anti-FHbp bactericidal titers were 2-fold lower in FHbp-FH(high) macaques against a strain with an exact FHbp match to the vaccine (P = .08) and were ≥4-fold lower against 4 mutants with other FHbp sequence variants (P ≤ .005, compared with FHbp-FH(low) macaques). Unexpectedly, postimmunization sera from all 12 macaques enhanced FH binding to meningococci. In contrast, serum anti-FHbp antibodies elicited by 4CMenB in mice whose mouse FH did not bind to the vaccine antigen inhibited FH binding.
  
  
  CONCLUSIONS
  Binding of FH to FHbp decreases protective anti-FHbp antibody responses of macaques to 4CMenB. Even low levels of FH binding skew the antibody repertoire to FHbp epitopes outside of the FH-binding site, which enhance FH binding.
authors: Center for Immunobiology and Vaccine Development, Children's Hospital Oakland Research Institute.
authors: Dan M
authors: DM
authors: Granoff
authors: Center for Immunobiology and Vaccine Development, Children's Hospital Oakland Research Institute.
authors: Isabella
authors: I
authors: Costa
authors: Center for Immunobiology and Vaccine Development, Children's Hospital Oakland Research Institute.
authors: Monica
authors: M
authors: Konar
authors: Center for Immunobiology and Vaccine Development, Children's Hospital Oakland Research Institute.
authors: Serena
authors: S
authors: Giuntini
authors: California National Primate Research Center, University of California-Davis, California.
authors: Koen K A
authors: KK
authors: Van Rompay
authors: Center for Immunobiology and Vaccine Development, Children's Hospital Oakland Research Institute.
authors: Peter T
authors: PT
authors: Beernink
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000907:Antibodies, Bacterial / Q000097:blood*; D000942:Antigens, Bacterial / Q000276:immunology* / Q000378:metabolism*; D001426:Bacterial Proteins / Q000276:immunology* / Q000378:metabolism*; D001770:Blood Bactericidal Activity; D017242:Complement Factor H / Q000378:metabolism*; D007108:Immune Tolerance; D008253:Macaca mulatta; D022401:Meningococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D008822:Mice, Transgenic; D038541:Neisseria meningitidis, Serogroup B / Q000276:immunology*; D011485:Protein Binding
chemical_list: C570015:4CMenB vaccine; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D022401:Meningococcal Vaccines; C484699:factor H-binding protein, Neisseria meningitidis; D017242:Complement Factor H
keywords: 4CMenB; Bexsero; FH; factor H binding protein; nonhuman primate animal model