title: Preclinical safety and immunogenicity evaluation of a nonavalent PorA native outer membrane vesicle vaccine against serogroup B meningococcal disease.
abstract: BACKGROUND
  An improved nonavalent PorA native outer membrane vesicle vaccine was developed with intrinsic adjuvating activity due to presence of less-toxic (lpxL1) LPS. In the present study, the safety and immunogenicity of this next-generation NonaMen vaccine were evaluated following repeated vaccination in rabbits and mice.
  
  
  METHODS
  A repeated-dose toxicology study was performed in rabbits. Immunogenicity of next-generation NonaMen was evaluated by determining the serum bactericidal antibody (SBA) titers against meningococcal serogroup B strains containing several PorA subtypes. Release of the pro-inflammatory cytokine, interleukin-6 (IL-6), by the human monocytic cell line (MM6) was measured to estimate pyrogenic activity.
  
  
  RESULTS
  No toxicologically relevant findings were noted in vaccinated rabbits receiving plain next-generation NonaMen. In agreement, next-generation NonaMen induced reduced amounts of the pro-inflammatory cytokine, IL-6, released by human monocyte cell line. In both rabbits and mice, next-generation NonaMen induced high SBA titers against all tested MenB strains regardless of whether or not aluminium phosphate adjuvant is used.
  
  
  CONCLUSIONS
  The data suggest that next-generation NonaMen is a safe vaccine with the potential to develop a broadly protective immune response and encourage the start of the first clinical studies.
authors.affiliation: Unit Vaccinology, Centre for Infectious Disease Control (CIb), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. patricia.kaaijk@rivm.nl
authors.forename: Patricia
authors.initials: P
authors.lastname: Kaaijk
authors.forename: Ineke
authors.initials: I
authors.lastname: van Straaten
authors.forename: Bas
authors.initials: B
authors.lastname: van de Waterbeemd
authors.forename: Elmieke P J
authors.initials: EP
authors.lastname: Boot
authors.forename: Lonneke M A R
authors.initials: LM
authors.lastname: Levels
authors.forename: Harry H
authors.initials: HH
authors.lastname: van Dijken
authors.forename: Germie P J M
authors.initials: GP
authors.lastname: van den Dobbelsteen
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects; D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000276:immunology*; D001770:Blood Bactericidal Activity; D005260:Female; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D022401:Meningococcal Vaccines / Q000009:adverse effects* / Q000276:immunology*; D051379:Mice; D050296:Microbial Viability; D009000:Monocytes / Q000276:immunology; D038541:Neisseria meningitidis, Serogroup B / Q000276:immunology*; D018272:Porins / Q000008:administration & dosage* / Q000009:adverse effects; D011817:Rabbits; D014611:Vaccination / Q000009:adverse effects / Q000379:methods
chemical_list: D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D015850:Interleukin-6; D022401:Meningococcal Vaccines; D018272:Porins; C057699:porin protein, Neisseria