Objective This proposal intends to apply Synthetic Biology to create a new bacterial species, Vaccinobacter, devoted to the production of multivalent, highly effective vaccines. The project originates from the evidence that Outer membrane Vesicles (OMVs) naturally produced by all Gram-negative bacteria can induce remarkable protective immunity, a property already exploited to develop anti-Neisseria vaccines now available for human use. OMV protection is mediated by the abundance of Pathogen-Associated-Molecular Patterns (PAMPs), known to play a key role in stimulating innate immunity. Moreover, OMVs can be engineered by delivering recombinant proteins to bacterial periplasm and outer membrane. Intrinsic adjuvanticity and propensity to be manipulated potentially make OMVs an ideal vaccine platform, particularly indicated when antigen combinations (for pathogens with genetic variability) and strong potentiation of immunity (for the elderly and cancer) are needed. However, full exploitation of OMVs as vaccines is prevented by: i) presence of potentially reactogenic compounds such as LPS, virulence factors, and toxins, ii) presence of several irrelevant proteins, which dilute immune responses, iii) lack of broadly applicable molecular tools to load OMVs with foreign antigens. Scope of the project is to provide novel solutions to solve these limitations and demonstrate the unique performance OMVs as vaccines by testing them on complex pathogens and cancer. Main project activities are: 1) remodelling of E. coli genome to create “Vaccinobacter”, a “living factory” of OMVs deprived of all unnecessary components but carrying the relevant immune potentiators, 2) characterization and optimization of the immune stimulatory properties of OMVs, 3) development of novel methods to incorporate foreign antigens into Vaccinobacter-derived OMVs, 4) loading of OMVs with selected pathogen- and cancer-derived antigens and demonstration of their protective efficacy in appropriate animal models. Fields of science natural sciencesbiological sciencesmicrobiologybacteriologynatural sciencesbiological sciencessynthetic biologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsvaccinesmedical and health sciencesclinical medicineoncology Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-AG-LS7 - ERC Advanced Grant - Diagnostic tools, therapies and public health Call for proposal ERC-2013-ADG See other projects for this call Funding Scheme ERC-AG - ERC Advanced Grant Host institution UNIVERSITA DEGLI STUDI DI TRENTO EU contribution € 1 859 840,07 Address VIA CALEPINA 14 38122 Trento Italy See on map Region Nord-Est Provincia Autonoma di Trento Trento Activity type Higher or Secondary Education Establishments Administrative Contact Vanessa Ravagni (Mrs.) Principal investigator Guido Grandi (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (3) Sort alphabetically Sort by EU Contribution Expand all Collapse all UNIVERSITA DEGLI STUDI DI TRENTO Italy EU contribution € 1 859 840,07 Address VIA CALEPINA 14 38122 Trento See on map Region Nord-Est Provincia Autonoma di Trento Trento Activity type Higher or Secondary Education Establishments Administrative Contact Vanessa Ravagni (Mrs.) Principal investigator Guido Grandi (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data EXTERNAUTICS SPA Participation ended Italy EU contribution € 255 837,88 Address VIA FIORENTINA 1 53100 SIENA See on map Activity type Private for-profit entities (excluding Higher or Secondary Education Establishments) Administrative Contact Paolo Sarmientos (Dr.) Links Contact the organisation Opens in new window Total cost No data FONDAZIONE TOSCANA LIFE SCIENCES Italy EU contribution € 497 150,05 Address VIA FIORENTINA 1 53100 Siena See on map Region Centro (IT) Toscana Siena Activity type Research Organisations Administrative Contact Ilaria Niccolai (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
