title: The first use of an investigational multicomponent meningococcal serogroup B vaccine (4CMenB) in humans.
abstract: BACKGROUND
  Neisseria meningitidis serogroup B is a well-recognized cause of bacterial meningitis and sepsis for which no broadly protective vaccine exists. Whole genome sequencing was used to identify three antigens: factor H binding protein (fHbp), Neisserial adhesin A (NadA), and Neisseria heparin binding antigen (NHBA) for an investigational vaccine candidate (rMenB). This was the first trial of an investigational multicomponent meningococcal serogroup B vaccine (4CMenB), containing rMenB and outer membrane vesicles (OMV) from the New Zealand epidemic strain in humans.
  
  
  RESULTS
  Seventy adults enrolled and received study vaccine. All vaccines were generally well tolerated. Immune responses were observed to multiple serogroup B strains following all investigational vaccines, suggesting the potential for broad coverage against this serogroup. Immunogenicity was enhanced by the addition of OMV; the 4CMenB displayed the optimal profile for further investigation.
  
  
  METHODS
  In a phase I, observer blind, randomized trial, healthy adults (18-40 years of age) were randomized 2:2:1 to receive 3 doses of 4CMenB, rMenB with OMV from the Norwegian outbreak strain, or rMenB alone. Pre- and postvaccination sera were evaluated in a serum bactericidal assay using human complement (hSBA) against a panel of 15 serogroup B strains, with titers ≥ 4 considered protective. Solicited injection site and systemic reactions were evaluated for 7 days following each vaccination and adverse events were reported throughout the study.
  
  
  CONCLUSIONS
  In this trial, 4CMenB displayed a favorable profile for further clinical development. 4CMenB demonstrated immunogenicity against multiple heterologous serogroup B strains. All vaccines were generally well tolerated in this study.
authors: Novartis Vaccines and Diagnostics, Cambridge, MA, USA.
authors: Daniela
authors: D
authors: Toneatto
authors: Shevqet
authors: S
authors: Ismaili
authors: Ellen
authors: E
authors: Ypma
authors: Kay
authors: K
authors: Vienken
authors: Philipp
authors: P
authors: Oster
authors: Peter
authors: P
authors: Dull
mesh_terms: D000293:Adolescent; D000328:Adult; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D005260:Female; D006801:Humans; D008297:Male; D022401:Meningococcal Vaccines / Q000276:immunology*; D038541:Neisseria meningitidis, Serogroup B / Q000276:immunology*; D011446:Prospective Studies
chemical_list: D001425:Bacterial Outer Membrane Proteins; D022401:Meningococcal Vaccines