Research Project
8833215
DESCRIPTION (provided by applicant): Pseudomonas aeruginosa (PA), an opportunistic Gram-negative bacterium, is one of the leading nosocomial pathogens worldwide. PA is responsible for localized infections of a variety of organ systems including respiratory, urinary, gastrointestinal, skin, eye, ear and joints and also systemic infections in susceptible individuals Because PA is highly adaptable to survive in common environments, mechanical ventilators, intravenous lines, urinary and dialysis catheters, pacemakers, and endoscopes can all be potential reservoirs for PA infections. Despite the widespread presence and growing significance of PA and the increasing rates of antibiotic treatment failure, no efficient and marketable vaccine is currently available. Recent advances in the development of anti-PA monoclonal antibodies (mAbs) have offered the possibility that passive immunotherapy may be a viable clinical modality. We are examining the treatment effectiveness of a combination of mAbs that can target two common PA LPS serotypes in one formulation using animal models infected with two virulent PA strains. The results will provide the basis for pre-clinical development of a combination PA therapy with an optimized glycosylation profile. The proposed work scope will allow us to determine 1) whether using plant derived manufacturing techniques could enhance manufacturing productivity, 2) whether manipulating glycosylation can achieve enhanced potency against bacterial challenge in two mouse models, and 3) the effectiveness of using a cocktail of two mAbs to target two common PA serotypes.
