Objective Tuberculosis is a leading killer world-wide, and the proportion of Paediatric tuberculosis is expanding. Although the BCG vaccine triggers specific T and B cell responses in neonates, it only confers protection from severe forms of tuberculosis in the firs t years of life. BCG does not significantly protect adults from pulmonary tuberculosis. There is therefore an urgent need to develop novel vaccines against tuberculosis, which would provide a long lasting protection following neonatal inoculation. One appr oach to this crucial aim is to decipher the mechanisms involved in neonatal immune responses to mycobacteria. For this purpose, we have established a consortium of experts in Genetics, Immunology, Microbiology and Paediatrics, as well as a biotechnology co mpany. Our objective is to dissect the molecular and cellular immune responses in neonates and infants, combining three complementary models, namely mice, humanized mice, and human patients. We will compare the innate and adaptive immune responses, with an emphasis on dendritic cells and T-cells. We will investigate neonatal and adult mice during mycobacterial infection and following inoculation of a novel and promising candidate vaccine, methylated HBHA. In addition, we will investigate such responses usin g mice reconstituted de novo with human lymphoid and myeloid hemopoietic-derived cell lineages, allowing for the first time an experimental dissection of human immunity to mycobacteria. The immune responses of naturally infected humans in the corresponding age groups will also be monitored and compared. Finally, the human molecular basis of hyper-susceptibility to live BCG in rare neonates with disseminated BCG disease will be investigated, in order to discover novel mycobacterial susceptibility genes, whic h will then be tested in the humanized mouse model. The feasibility of this research programme is attested by the high scientific quality and remarkable complementarity of the participants. Fields of science natural sciencesbiological sciencesgeneticsmedical and health sciencesbasic medicineimmunologymedical and health sciencesclinical medicinepneumologytuberculosismedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsvaccinesmedical and health sciencesclinical medicinepaediatrics Programme(s) FP6-LIFESCIHEALTH - Life sciences, genomics and biotechnology for health: Thematic Priority 1 under the Focusing and Integrating Community Research programme 2002-2006. Topic(s) LSH-2004-2.3.0-5 - Neonatal immunity Call for proposal FP6-2004-LIFESCIHEALTH-5 See other projects for this call Funding Scheme STREP - Specific Targeted Research Project Coordinator KAROLINSKA INSTITUTET EU contribution No data Address Nobels väg 5 STOCKHOLM Sweden See on map Links Website Opens in new window Total cost No data Participants (7) Sort alphabetically Sort by EU Contribution Expand all Collapse all STOCKHOLMS UNIVERSITET Sweden EU contribution No data Address Universitetsv. 10 STOCKHOLM See on map Links Website Opens in new window Total cost No data UNIVERSITY OF GLASGOW United Kingdom EU contribution No data Address University Avenue GLASGOW See on map Links Website Opens in new window Total cost No data INSTITUT PASTEUR DE LILLE France EU contribution No data Address Rue du Pr. Calmette 1 LILLE See on map Links Website Opens in new window Total cost No data UNIVERSITE LIBRE DE BRUXELLES Belgium EU contribution No data Address 50 Avenue Franklin Roosevelt BRUSSELS See on map Links Website Opens in new window Total cost No data LIONEX DIAGNOSTICS & THERAPEUTICS GMBH Germany EU contribution No data Address Mascheroder Weg 1b BRAUNSCHWEIG See on map Links Website Opens in new window Total cost No data INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE France EU contribution No data Address 2 rue d'Alesia PARIS See on map Links Website Opens in new window Total cost No data INSTITUTO SUPERIORE DI SANITÀ Italy EU contribution No data Address Viale Regina Elena, 299 ROME See on map Links Website Opens in new window Total cost No data
