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 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.

Original publication

DOI

10.1016/j.jinf.2015.05.006

Type

Journal article

Journal

J Infect

Publication Date

09/2015

Volume

71

Pages

326 - 337

Keywords

FetA, Molecular epidemiology, Neisseria meningitidis, Outer membrane vesicles, Vaccine, Adolescent, Adult, Antibodies, Bacterial, Bacterial Outer Membrane Proteins, Carrier Proteins, Female, Humans, Male, Meningococcal Vaccines, Middle Aged, Molecular Epidemiology, Neisseria meningitidis, Serogroup B, Porins, Receptors, Cell Surface, Serum Bactericidal Antibody Assay, Young Adult