title: A novel meningococcal outer membrane vesicle vaccine with constitutive expression of FetA: A phase I clinical trial.
abstract: OBJECTIVE
  Outer membrane vesicle (OMV) vaccines are used against outbreaks of capsular group B Neisseria meningitidis (MenB) caused by strains expressing particular PorA outer membrane proteins (OMPs). Ferric enterobactin receptor (FetA) is another variable OMP that induces type-specific bactericidal antibodies, and the combination of judiciously chosen PorA and FetA variants in vaccine formulations is a potential approach to broaden protection of such vaccines.
  
  
  METHODS
  The OMV vaccine MenPF-1 was generated by genetically modifying N. meningitidis strain 44/76 to constitutively express FetA. Three doses of 25 μg or 50 μg of MenPF-1 were delivered intra-muscularly to 52 healthy adults.
  
  
  RESULTS
  MenPF-1 was safe and well tolerated. Immunogenicity was measured by serum bactericidal assay (SBA) against wild-type and isogenic mutant strains. After 3 doses, the proportion of volunteers with SBA titres ≥1:4 (the putative protective titre) was 98% for the wild-type strain, and 77% for the strain 44/76 FetA(on)PorA(off) compared to 51% in the strain 44/76 FetA(off)PorA(off), demonstrating that vaccination with MenPF-1 simultaneously induced FetA and PorA bactericidal antibodies.
  
  
  CONCLUSIONS
  This study provides a proof-of-concept for generating bactericidal antibodies against FetA after OMV vaccination in humans. Prevalence-based choice of PorA and FetA types can be used to formulate a vaccine for broad protection against MenB disease.
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, CCVTM, Churchill Lane, Oxford OX37LE, United Kingdom.
authors.forename: L
authors.initials: L
authors.lastname: Marsay
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, CCVTM, Churchill Lane, Oxford OX37LE, United Kingdom.
authors.forename: C
authors.initials: C
authors.lastname: Dold
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, CCVTM, Churchill Lane, Oxford OX37LE, United Kingdom.
authors.forename: C A
authors.initials: CA
authors.lastname: Green
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, CCVTM, Churchill Lane, Oxford OX37LE, United Kingdom. Electronic address: christine.rollier@paediatrics.ox.ac.uk.
authors.forename: C S
authors.initials: CS
authors.lastname: Rollier
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, CCVTM, Churchill Lane, Oxford OX37LE, United Kingdom.
authors.forename: G
authors.initials: G
authors.lastname: Norheim
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, CCVTM, Churchill Lane, Oxford OX37LE, United Kingdom.
authors.forename: M
authors.initials: M
authors.lastname: Sadarangani
authors.affiliation: Nuffield Department of Primary Health Care Sciences, Primary Care Clinical Trials Unit, University of Oxford, 23-38 Hythe Bridge Street, Oxford, United Kingdom.
authors.forename: M
authors.initials: M
authors.lastname: Shanyinde
authors.affiliation: Department of Zoology, University of Oxford, South Parks Road, United Kingdom.
authors.forename: C
authors.initials: C
authors.lastname: Brehony
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, CCVTM, Churchill Lane, Oxford OX37LE, United Kingdom.
authors.forename: A J
authors.initials: AJ
authors.lastname: Thompson
authors.affiliation: National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Potters Bar, Hertfordshire, United Kingdom.
authors.forename: H
authors.initials: H
authors.lastname: Sanders
authors.affiliation: National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Potters Bar, Hertfordshire, United Kingdom.
authors.forename: H
authors.initials: H
authors.lastname: Chan
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, CCVTM, Churchill Lane, Oxford OX37LE, United Kingdom.
authors.forename: K
authors.initials: K
authors.lastname: Haworth
authors.affiliation: Michael Smith Building, Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: J P
authors.initials: JP
authors.lastname: Derrick
authors.affiliation: National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Potters Bar, Hertfordshire, United Kingdom.
authors.forename: I M
authors.initials: IM
authors.lastname: Feavers
authors.affiliation: Department of Zoology, University of Oxford, South Parks Road, United Kingdom.
authors.forename: M C
authors.initials: MC
authors.lastname: Maiden
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, CCVTM, Churchill Lane, Oxford OX37LE, United Kingdom.
authors.forename: A J
authors.initials: AJ
authors.lastname: Pollard
mesh_terms: D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D001425:Bacterial Outer Membrane Proteins / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology; D002352:Carrier Proteins / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D022401:Meningococcal Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D008875:Middle Aged; D017720:Molecular Epidemiology; D038541:Neisseria meningitidis, Serogroup B / Q000235:genetics* / Q000276:immunology*; D018272:Porins / Q000235:genetics / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology*; D058248:Serum Bactericidal Antibody Assay; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; C093120:FrpB protein, bacteria; D022401:Meningococcal Vaccines; D018272:Porins; D011956:Receptors, Cell Surface; C029489:enterobactin receptor; C057699:porin protein, Neisseria
keywords: FetA; Molecular epidemiology; Neisseria meningitidis; Outer membrane vesicles; Vaccine