Development of antibody treatment of MDR ESKAPE Pathogen, P. Aeruginosa.

In Phase I, Fabrico Technology and Professor Jennifer Maynard, the Z. D. Bonner Professorship of Chemical Engineering, of the University of Texas at Austin, provided proof-of-concept in the development of state-of-the-art infrastructural systems, methods and protocols to identify and isolate bacterial surface antigens of P. aeruginosa that elicit strong response of antibodies from infected patients. Fabrico Technology and Professor Maynard proposes to generate nanobodies targeting unique epitopes of these antigens identified and isolated in the Phase I. The Maynard lab will develop a novel antibody-like protein therapeutic to potently redirect human immune responses to bacterial killing. Specifically, transgenic nanomice will be immunized with the selected antigens and the mouse spleens will be used as a source of nanobodies. These nanobodies will be optimized and then tested and evaluated for bacterial killing in-vitro and in-vivo mouse model of the disease. Nanobodies represent a novel approach which are characteristically stable, can withstand high temperature conditions that are present in battlefield environments, and can be multimerized to increase affinity and simultaneously target multiple antigens. Fusing nanobodies to human IgG1 Fc domains will enhance the product manufacturability and confer long in vivo half-lives. Moreover, we will use Fc domains engineered to potently mediate bactericidal activities (phagocytosis and complement-mediated killing). We envision this product can be freeze-dried for deployment to battlefield situations, where it can be combined with recently FDA-approved freeze-dried blood before administration to injured soldiers to prevent this common wound infection and other future MDR ESKAPE pathogens and infections.