Project description DEENESFRITPL Dissecting the invasiveness of meningococcal infections Recent years have witnessed a re-emergence of the meningococcal serogroup W type-11 strain which demonstrates increased invasiveness. To address this medical challenge, the EU-funded EpIg Men project will investigate the virulence factors responsible for the invasiveness of this strain and whether antibodies can still clear the pathogen. In particular, researchers will study the mechanisms underlying the interaction of meningococcal bacteria with epithelial cells and evaluate the ability of antibodies from different age groups to protect against infection. Results will help formulate novel public protection measures and potentially identify novel targets for therapies as well as vaccine design. Show the project objective Hide the project objective Objective 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. Fields of science social sciencessociologydemographymortalitymedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsvaccines Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2018 - Individual Fellowships Call for proposal H2020-MSCA-IF-2018 See other projects for this call Funding Scheme MSCA-IF-EF-RI - RI – Reintegration panel Coordinator RIJKSINSTITUUT VOOR VOLKSGEZONDHEID EN MILIEU Net EU contribution € 187 572,48 Address Antonie Van Leeuwenhoeklaan 9 3721 MA Bilthoven Netherlands See on map Region West-Nederland Utrecht Utrecht Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 187 572,48
