Objectif Antimicrobial Resistance (AMR) is perhaps the most emerging alarm in health. It already causes 700,000 deaths per year and the forecast for 2050 is 10 million deaths, more than cancer today. WHO, UN General Assembly, World Bank, G20, EU, UK and USA governments call for new antibiotics, but the pipeline for new antibiotics is not very promising. Here we propose to use new technologies to develop human monoclonal antibodies and vaccines against three AMR bacteria such as gonococcus, pneumococcus and E.coli. The technology defined as reverse vaccinology 2.0 already successful for viral infections, will be used for bacterial vaccines. Taking advantage of the recent possibility of high throughput cloning of human B cells from convalescent or vaccinated people we aim to find targets difficult or impossible to be discovered using conventional technologies. B cells will be cloned from people convalescent from target infections and from people vaccinated with Men B vaccine which confers some protection against gonococcus. The antibodies produced by the clones will be screened for their ability to bind, intoxicate or kill bacteria using a novel high-throughput microscopy platform that rapidly captures digital images and also with conventional, lower throughput technologies such as bactericidal, opsono-phagocytosis and FACS assays. The selected antibodies, will be expressed as full length and used for passive immunization in animal models and tested for protection in vivo. Finally, those antibodies that will provide the best protection in the above assays, will be used to identify the recognized antigens. Selected antigens will be expressed and tested in vaccine formulations. Fab fragments can be used to make co-crystals with the antigen and determine the crystal structure of the new antigens, for the development of structure-based antigen design. In conclusion we expect to enable development of human monoclonal antibodies and vaccines against AMR. Champ scientifique natural sciencesbiological sciencesmicrobiologybacteriologymedical and health sciencesbasic medicineimmunologyimmunisationmedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsvaccinesmedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantibioticsmedical and health sciencesbasic medicinepharmacology and pharmacydrug resistanceantibiotic resistance Mots‑clés Vaccines Infectious Diseases Monoclonal antibodies Antimicrobial resistance (AMR) Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Thème(s) ERC-2017-ADG - ERC Advanced Grant Appel à propositions ERC-2017-ADG Voir d’autres projets de cet appel Régime de financement ERC-ADG - Advanced Grant Institution d’accueil FONDAZIONE TOSCANA LIFE SCIENCES Contribution nette de l'UE € 2 432 500,00 Adresse VIA FIORENTINA 1 53100 Siena Italie Voir sur la carte Région Centro (IT) Toscana Siena Type d’activité Research Organisations Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 2 432 500,00 Bénéficiaires (1) Trier par ordre alphabétique Trier par contribution nette de l'UE Tout développer Tout réduire FONDAZIONE TOSCANA LIFE SCIENCES Italie Contribution nette de l'UE € 2 432 500,00 Adresse VIA FIORENTINA 1 53100 Siena Voir sur la carte Région Centro (IT) Toscana Siena Type d’activité Research Organisations Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 2 432 500,00
