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

Marsay L., Dold C., Green CA., Rollier CS., Norheim G., Sadarangani M., Shanyinde M., Brehony C., Thompson AJ., Sanders H., Chan H., Haworth K., Derrick JP., Feavers IM., Maiden MC., Pollard AJ.

© 2015 The British Infection Association. 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 25μg or 50μg 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. 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.

DOI

10.1016/j.jinf.2015.05.006

Type

Journal article

Publication Date

2015-01-01T00:00:00+00:00

Permalink More information Close