A Whole Cell Metal-Organic Framework Encapsulated Vaccine Against Septicemic UPEC Infection

Urinary tract infection, most often caused by uropathogenic (UPEC), is the second most common bacterial infection. Rates of antibiotic resistance among UPEC strains is high and front-line antibiotic therapies are losing efficacy. Untreated, UPEC can ascend to the kidneys and into the bloodstream to cause potentially fatal pyelonephritis and bacteremia, respectively. Vaccine development is hampered by the genetic diversity of UPEC strains making selection of antigens capable of inducing broad protection difficult. Whole cell UPEC vaccines offer a solution to the antigen selection problem, however, current inactivation methods are harsh and degrade surface antigens resulting in a weak immune response. Here, we demonstrate a method to gently inactivate whole cell UPEC by encasing them in a crystalline metal-coordination polymeric matrix called a Metal-Organic Framework. This process encapsulates read-to-use composites within 30 minutes in water and at ambient temperatures. We show this new formulation greatly improves survivability in a murine model of UPEC bacteremia compared to standard inactivated formulations. The simplicity of the preparation and use suggests this method could be applied as a point-of-care measure to create therapeutic and prophylactic vaccines against patient derived samples.