title: A native outer membrane vesicle vaccine confers protection against meningococcal colonization in human CEACAM1 transgenic mice.
abstract: BACKGROUND
  The effect of protein-based meningococcal vaccines on prevention of nasopharyngeal colonization has been difficult to investigate experimentally because a reliable animal colonization model did not exist.
  
  
  METHODS
  Human CEACAM1 transgenic mice, which can be colonized by meningococci, were immunized IP with one of two meningococcal native outer membrane vesicle (NOMV) vaccines prepared from mutants with attenuated endotoxin (lpxL1 knockout) and over-expressed sub-family B Factor H-binding proteins (FHbp). Animals were challenged intranasally two weeks after the third dose with wild-type strain H44/76, or were treated IP with anti-NOMV serum before and during the bacterial challenge.
  
  
  RESULTS
  The NOMV-1 vaccine, prepared from the serogroup B H44/76 mutant, elicited ∼40-fold higher serum bactericidal antibody titers against the wild-type H44/76 challenge strain than the NOMV-2 vaccine prepared from a heterologous serogroup W mutant strain with different PorA and FHbp amino acid sequence variants. Compared to aluminum hydroxide-immunized control mice, the efficacy for prevention of any H44/76 colonization was 93% (95% confidence interval, 52-99, P<0.0001) for the NOMV-1 vaccine, and 19% (-3-36, P=0.23) for NOMV-2. NOMV-2-vaccinated mice had a 5.6-fold decrease in geometric mean CFU of bacteria per animal in tracheal washes compared to control mice (P=0.007). The efficacy of passive administration of serum from NOMV-1-vaccinated mice to immunologically naïve mice against colonization was 44% (17-61; P=0.002).
  
  
  CONCLUSIONS
  Both NOMV vaccines protected against meningococcal colonization but there was greater protection by the NOMV-1 vaccine with antigens matched with the challenge strain. Meningococcal vaccines that target protein antigens have potential to decrease colonization.
authors: Center for Immunobiology and Vaccine Development, Children's Hospital Oakland Research Institute, Oakland, CA 94609 USA.
authors: Rolando
authors: R
authors: Pajon
authors: Department of Molecular Genetics, University of Toronto, Toronto, Ontario Canada.
authors: Carolyn M
authors: CM
authors: Buckwalter
authors: Department of Molecular Genetics, University of Toronto, Toronto, Ontario Canada.
authors: Kay O
authors: KO
authors: Johswich
authors: Department of Molecular Genetics, University of Toronto, Toronto, Ontario Canada.
authors: Scott D
authors: SD
authors: Gray-Owen
authors: Center for Immunobiology and Vaccine Development, Children's Hospital Oakland Research Institute, Oakland, CA 94609 USA.
authors: Dan M
authors: DM
authors: Granoff
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood*; D000942:Antigens, Bacterial / Q000235:genetics; D015703:Antigens, CD / Q000235:genetics; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000235:genetics; D004731:Endotoxins / Q000276:immunology; D006801:Humans; D007116:Immunization, Passive; D007274:Injections, Intraperitoneal; D008589:Meningococcal Infections / Q000517:prevention & control; D022401:Meningococcal Vaccines / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009305:Nasopharynx / Q000382:microbiology*; D009345:Neisseria meningitidis / Q000254:growth & development* / Q000276:immunology; D038541:Neisseria meningitidis, Serogroup B / Q000254:growth & development / Q000276:immunology*; D058248:Serum Bactericidal Antibody Assay; D014611:Vaccination
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D015703:Antigens, CD; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D004731:Endotoxins; D022401:Meningococcal Vaccines; C484699:factor H-binding protein, Neisseria meningitidis
keywords: Colonization model; FHbp; Factor H binding protein; Neisseria meningitidis; OMV; PorA; Vaccine