Ziel
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.
Wissenschaftliches Gebiet
- social sciencesmedia and communicationsgraphic design
- medical and health sciencesbasic medicineimmunologyimmunisation
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsvaccines
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantibiotics
- medical and health sciencesbasic medicinepharmacology and pharmacydrug resistanceantibiotic resistance
Schlüsselbegriffe
Programm/Programme
Thema/Themen
Finanzierungsplan
ERC-ADG - Advanced GrantGastgebende Einrichtung
53100 Siena
Italien