A novel meningococcal outer membrane vesicle vaccine with constitutive expression of FetA: A phase I clinical trial.

Research output: Contribution to journalArticle

Authors

  • Leanne Marsay
  • Christina Dold
  • Christine Rollier
  • Gunnstein Norheim
  • Manish Sadarangani
  • Milensu Shanyinde
  • Carina Brehony
  • Amber Thompson
  • Holly Sanders
  • Hannah Chan
  • Kathryn Haworth
  • Jeremy Derrick
  • Ian Feavers
  • Martin Maiden
  • Andrew Pollard

External organisations

  • Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, United Kingdom.
  • Nuffield Department of Primary Care Health Sciences
  • Department of Zoology, University of Oxford
  • National Institute for Biological Standards and Control (NIBSC)
  • University of Manchester

Abstract

Objectives: 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 pro- tection 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 mg or 50 mg of MenPF-1 were delivered intra-muscularly to 52 healthy adults. Results: MenPF-1 was safe and well tolerated. Immunogenicity was measured by serum bacte- ricidal 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 FetAonPorAoff compared to 51% in the strain 44/76 FetAoffPorAoff, demonstrating that vaccination with MenPF-1 simultaneously induced FetA and PorA bactericidal antibodies. Conclusion: 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.

Details

Original languageEnglish
JournalJournal of Infection
Publication statusPublished - 2015
Externally publishedYes