Human monoclonal antibodies against Shigella (ShiMabs), for therapy and vaccine acceleration

The project is expected to contribute significantly to a flagship approach to Shigella and to accelerate the development of an ultimate remedy to shigellosis. This will be done by i) developing human monoclonal antibodies (mAbs) against Shigella that overcome antimicrobial resistance (AMR) and are affordable in low- and middle-income countries (LMIC); ii) establishing standard correlates of protection which will accelerate development and recommendation of antibodies and vaccines; iii) providing the bases for universal vaccines by identifying novel protective antigens common to all serotypes or common epitopes present in the lipopolysaccharide of all serotypes. We will take advantage of the recent possibility of high-throughput cloning of human B cells from convalescent or vaccinated people to find targets difficult or impossible to be discovered using conventional technologies. We will apply for the first time high-content confocal microscopy screening of human mAbs interacting with bacteria and we will use machine Learning and artificial intelligence to analyze high-quality digital images to detect antibodies that bind, intoxicate or kill bacteria. The development of effective mAbs and vaccines against AMR bacteria is one of the best approaches to fight AMR since they can reduce the overall use of antibiotics and decrease the incidence of resistant infections.