Objetivo Glycoconjugate vaccines have provided enormous health benefits globally, but they have been less successful in some populations at high risk for developing disease. They are composed by a sugar antigen covalently linked to a carrier protein. The traditional hypothesis of immune activation by glycoconjugate vaccines suggests that only peptides generated from glycoconjugate processing can be presented to and recognized by T cells, and this contribution is crucial for their immunogenicity. In most cases, conjugation processes have been set-up empirically.Recently, new findings offer a rational explanation for how conjugates work and may render vaccine development a more straightforward process. In contrast with the classical mechanism, this new model suggests that carbohydrate presentation to the T cell by antigen-presenting cell may strongly enhance antibody response. The keystrategy is to conjugate the carbohydrate to peptides which anchor the conjugate via MHC class II and allow the sugar epitope to be presented via the T cell receptor. Application of this principle resulted in a GBSIII vaccine strongly protective in a mouse model and 50–100 times more immunogenic than a traditional vaccine composed byrandom linking of the sugar on a protein carrier. Although the principle has been demonstrated much remains to be done to generally apply the concept to generate vaccines for clinical use. In the proposed study, we will extend the approach by analysing different variables (peptide carrier, glycan chain length, conjugation chemistry and microbial antigen), with the aim of using the increased understanding of basic immunological mechanisms to develop a new translational platform for optimized and cost-effective carbohydrate-based vaccines. Innovative strategies of conjugation chemistry will be also evaluated to generate new therapeutics with chemical properties designed in light of specific information on antigen presentation. Ámbito científico medical and health sciencesbasic medicineimmunologyimmunisationmedical and health scienceshealth sciencesinfectious diseasesnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsvaccinesnatural sciencesbiological sciencesbiochemistrybiomoleculescarbohydrates Programa(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 Tema(s) MSCA-IF-2014-GF - Marie Skłodowska-Curie Individual Fellowships (IF-GF) Convocatoria de propuestas H2020-MSCA-IF-2014 Consulte otros proyectos de esta convocatoria Régimen de financiación MSCA-IF-GF - Global Fellowships Coordinador UNIVERSITA DEGLI STUDI DI MILANO Aportación neta de la UEn € 244 269,00 Dirección Via Festa Del Perdono 7 20122 Milano Italia Ver en el mapa Región Nord-Ovest Lombardia Milano Tipo de actividad Higher or Secondary Education Establishments Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Participación en los programas de I+D de la UE Opens in new window Red de colaboración de HORIZON Opens in new window Coste total € 244 269,00 Participantes (1) Ordenar alfabéticamente Ordenar por aportación neta de la UE Ampliar todo Contraer todo GLAXOSMITHKLINE VACCINES SRL La participación finalizó Italia Aportación neta de la UEn € 0,00 Dirección VIA FIORENTINA 1 53100 SIENA Ver en el mapa Región Centro (IT) Toscana Siena Tipo de actividad Private for-profit entities (excluding Higher or Secondary Education Establishments) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Participación en los programas de I+D de la UE Opens in new window Red de colaboración de HORIZON Opens in new window Coste total Sin datos Socios (1) Ordenar alfabéticamente Ordenar por aportación neta de la UE Ampliar todo Contraer todo Socio Las organizaciones asociadas contribuyen a la aplicación de la acción, pero no firman el acuerdo de subvención. PRESIDENT AND FELLOWS OF HARVARD COLLEGE Estados Unidos Aportación neta de la UEn € 0,00 Dirección MASSACHUSETTS AVENUE 1350 02138 Cambridge Ver en el mapa Tipo de actividad Higher or Secondary Education Establishments Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Participación en los programas de I+D de la UE Opens in new window Red de colaboración de HORIZON Opens in new window Coste total € 160 130,40
