The Role of Antibodies (Ig) and the Respiratory Epithelium in the Prevention of Invasive Meningococcal Infections in Different Age Groups

ended

Highly invasive meningococcal infections with serogroup W of clonal type cc11 are rapidly increasing and have a high (16-25%) mortality rate. The aim of this project is to investigate why recent isolates are invasive and how different antibodies can protect. Special focus will be on protection of epithelial cells of the wall of the respiratory tract as prevention of infection may be key to protect the public against infection with MenW cc11. Recent clinical isolates of different clinical invasiveness will be subjected to pangenetic analyses to identify virulence factors. The ability of these isolates to infect epithelial cells will be evaluated to compare virulence factors with functional invasiveness. I then will analyse meningococcal-specific antibody levels in serum and saliva in different age groups with increased carriage and/or risk of meningococcal invasive disease. The antibodies will be evaluated for their ability to protect against infection in two different functional assays: prevention of infection of respiratory epithelial cells and the gold standard serum bactericidal assay that predicts the ability to clear invaded meningococci. Finally, epithelial responses to meningococci and modulation of these responses will be investigated. These studies will analyse cytokine and chemokine production, and the production of antibodies by B cells in epithelial-B cell co-cultures. Together, these data will a) help to identify meningococcal virulence factors and the invasiveness of MenW cc11 relative to other isolates, b) identify levels and functional ability of antibodies to protect against infection in groups at increased risk, c) help in defining a novel correlate of protection and d) reveal meningococcal-epithelial interactions. The results will provide insight for vaccine design, vaccination policy and surveillance strategies.