title: A meningococcal NOMV-FHbp vaccine for Africa elicits broader serum bactericidal antibody responses against serogroup B and non-B strains than a licensed serogroup B vaccine.
abstract: BACKGROUND
  Meningococcal epidemics in Sub-Sahara caused by serogroup A strains are controlled by a group A polysaccharide conjugate vaccine. Strains with serogroups C, W and X continue to cause epidemics. Protein antigens in licensed serogroup B vaccines are shared among serogroup B and non-B strains.
  
  
  OBJECTIVE
  Compare serum bactericidal antibody responses elicited by an investigational native outer membrane vesicle vaccine with over-expressed Factor H binding protein (NOMV-FHbp) and a licensed serogroup B vaccine (MenB-4C) against African serogroup A, B, C, W and X strains.
  
  
  METHODS
  Human Factor H (FH) transgenic mice were immunized with NOMV-FHbp prepared from a mutant African meningococcal strain containing genetically attenuated endotoxin and a mutant sub-family B FHbp antigen with low FH binding, or with MenB-4C, which contains a recombinant sub-family B FHbp antigen that binds human FH, and three other antigens, NHba, NadA and PorA P1.4, capable of eliciting bactericidal antibody.
  
  
  RESULTS
  The NOMV-FHbp elicited serum bactericidal activity against 12 of 13 serogroup A, B, W or X strains from Africa, and four isogenic serogroup B mutants with sub-family B FHbp sequence variants. There was no activity against a serogroup B mutant with sub-family A FHbp, or two serogroup C isolates from a recent outbreak in Northern Nigeria, which were mismatched for both PorA and sub-family of the FHbp vaccine antigen. For MenB-4C, NHba was expressed by all 16 African isolates tested, FHbp sub-family B in 13, and NadA in five. However, MenB-4C elicited titers ≥ 1:10 against only one isolate, and against only two of four serogroup B mutant strains with sub-family B FHbp sequence variants.
  
  
  CONCLUSIONS
  NOMV-FHbp has greater potential to confer serogroup-independent protection in Africa than the licensed MenB-4C vaccine. However, the NOMV-FHbp vaccine will require inclusion of sub-family A FHbp for coverage against recent serogroup C strains causing outbreaks in Northern Nigeria.
authors.affiliation: Center for Immunobiology and Vaccine Development, UCSF Benioff Children's Hospital Oakland Research Institute, Oakland, CA, USA.
authors.forename: Rolando
authors.initials: R
authors.lastname: Pajon
authors.affiliation: Center for Immunobiology and Vaccine Development, UCSF Benioff Children's Hospital Oakland Research Institute, Oakland, CA, USA.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Lujan
authors.affiliation: Center for Immunobiology and Vaccine Development, UCSF Benioff Children's Hospital Oakland Research Institute, Oakland, CA, USA. Electronic address: dgranoff@chori.org.
authors.forename: Dan M
authors.initials: DM
authors.lastname: Granoff
mesh_terms: D018829:Adhesins, Bacterial / Q000276:immunology; D000349:Africa; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood*; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D017242:Complement Factor H / Q000235:genetics; D008589:Meningococcal Infections / Q000517:prevention & control*; D022401:Meningococcal Vaccines / Q000276:immunology*; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D038541:Neisseria meningitidis, Serogroup B; D009549:Nigeria; D018272:Porins / Q000276:immunology; D065288:Serogroup; D058248:Serum Bactericidal Antibody Assay
chemical_list: D018829:Adhesins, Bacterial; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C493495:CFH protein, human; D022401:Meningococcal Vaccines; C501982:NadA protein, Neisseria meningitidis; D018272:Porins; C484699:factor H-binding protein, Neisseria meningitidis; C057699:porin protein, Neisseria; D017242:Complement Factor H
keywords: Bexsero; Complement; Factor H; Factor H-binding protein; Neisseria meningitidis; OMV; Outer membrane vesicle; Transgenic mouse; Vaccine