Therapeutic human monoclonal antibodies against multidrug resistant bacteria via combined high-potential target identification, single B cell antibody isolation and structural approaches – HUMABACT

Multi drug resistant (MDR) bacteria, notably Klebsiella pneumoniae (Kp) and Pseudomonas aeruginosa (Pa), are a major global threat. The development of alternative anti-infectious therapies is thus crucial. In this respect, monoclonal antibodies (mAbs) targeting bacterial virulence factors offer highly promising perspectives. To accelerate the discovery of antibacterial therapeutic mAbs, we propose a highly innovative pipeline combining: i) the identification - through combined reverse vaccinology and functional genetics - and careful selection of virulence factors as high potential targets and design of associated robust functional assays; ii) the rational design, based on structural studies, of corresponding baits for an optimized specific B cell isolation; and iii) state of the art mAb isolation methods from single B cells from infected and convalescent individuals. The program will yield a large panel of fully human mAbs with strong therapeutic potential against Pa and Kp.