Pseudomonas antibodies with designed glycans

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 whether using plant derived manufacturing techniques could enhance manufacturing productivity whether manipulating glycosylation can achieve enhanced potency against bacterial challenge in two mouse models and the effectiveness of using a cocktail of two mAbs to target two common PA serotypes PUBLIC HEALTH RELEVANCE We are developing two IgM monoclonal antibodies for the treatment of Pseudomonas aeruginosa infections The antibody manufacturing system involves plant based production and glycol engineering The goal is to develop a PA therapy using a cocktail of two mAbs to target two common PA serotypes