Objective 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. Fields of science medical and health sciencesbasic medicineimmunologyimmunisationmedical and health scienceshealth sciencesinfectious diseasesnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsvaccinesnatural sciencesbiological sciencesbiochemistrybiomoleculescarbohydrates 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-2014-GF - Marie Skłodowska-Curie Individual Fellowships (IF-GF) Call for proposal H2020-MSCA-IF-2014 See other projects for this call Funding Scheme MSCA-IF-GF - Global Fellowships Coordinator UNIVERSITA DEGLI STUDI DI MILANO Net EU contribution € 244 269,00 Address Via festa del perdono 7 20122 Milano Italy See on map Region Nord-Ovest Lombardia Milano Activity type Higher or Secondary Education Establishments 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 Other funding € 0,00 Participants (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all GLAXOSMITHKLINE VACCINES SRL Participation ended Italy Net EU contribution € 0,00 Address Via fiorentina 1 53100 Siena See on map Region Centro (IT) Toscana Siena Activity type Private for-profit entities (excluding Higher or Secondary Education Establishments) 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 Other funding € 0,00 Partners (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all Partner Partner organisations contribute to the implementation of the action, but do not sign the Grant Agreement. PRESIDENT AND FELLOWS OF HARVARD COLLEGE United States Net EU contribution € 0,00 Address Massachusetts avenue 1350 02138 Cambridge See on map Activity type Higher or Secondary Education Establishments 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 Other funding € 160 130,40
