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


ABSTRACT: 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.The OMV vaccine MenPF-1 was generated by genetically modifying N. meningitidis strain 44/76 to constitutively express FetA. Three doses of 25 ?g or 50 ?g of MenPF-1 were delivered intra-muscularly to 52 healthy adults.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.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.

SUBMITTER: Marsay L 

PROVIDER: S-EPMC4535279 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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

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

The Journal of infection 20150515 3


<h4>Objectives</h4>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.<h4>Methods</h4>The OMV v  ...[more]

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