A novel meningococcal outer membrane vesicle vaccine with constitutive expression of FetA: A phase I clinical trial - 03/08/15
, G. Norheim a, M. Sadarangani a, M. Shanyinde b, C. Brehony c, A.J. Thompson a, H. Sanders d, H. Chan d, K. Haworth a, J.P. Derrick e, I.M. Feavers d, M.C. Maiden c, A.J. Pollard aSummary |
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.
Le texte complet de cet article est disponible en PDF.Highlights |
• | MenB OMV vaccines' efficacy is strain-restricted by the variable antigen PorA. |
• | FetA is another variable antigen, but has iron-dependent expression. |
• | The combination of only a few PorA and FetA can induce broad-protection. |
• | A mutated OMV was created containing one PorA and one FetA. |
• | FetA induces bactericidal antibody response in addition to the PorA response in a Phase I trial. |
Keywords : Neisseria meningitidis, Vaccine, Outer membrane vesicles, FetA, Molecular epidemiology
Plan
Vol 71 - N° 3
P. 326-337 - septembre 2015 Retour au numéro
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