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

Leanne Marsay, Christina Dold, Christopher Green, 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

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)
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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 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 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.

Original languageEnglish
Pages (from-to)326-337
Number of pages12
JournalJournal of Infection
Volume71
Issue number3
Early online date15 May 2015
DOIs
Publication statusPublished - Sept 2015

Keywords

  • Neisseria meningitidis
  • Vaccine
  • outer membrane vesicles
  • FetA
  • Molecular epidemiology

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