This project was a collaborative effort between Lawrence Livermore National Security, LLC as manager and operator of Lawrence Livermore National Laboratory (LLNL) and Syntiron LLC to develop novel vaccine formulations against bacterial urinary tract infections (UTIs). The project leveraged expertise at Syntiron to develop vaccine antigens for bacterial pathogens and nanoparticle technology at LLNL to enchance the efficacy of vaccine formulations. In particular, Syntiron has developed vaccine antigens by identifying and isolating specific proteins from the membranes of extraintestinal pathogenic <
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E. coli<
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, the bacteria responsible for the majority of UTIs. These membrane protein antigens consist of iron regulating proteins (IRPs), a class of highly conserved putative antigens. Membrane protein antigens are difficult to formulate for vaccine applications. The formulations typically required to solubilize membrane protein antigens often result in non-native protein folding, thereby masking the antigenic epitopes required for efficacy. LLNL's nanolipoprotein particle (NLP) platform provides a mimic of a membrane protein's native environment, greatly increasing the proteins' native attributes. In addition, the NLP can accommodate myriad other biomolecules in addition to the protein antigen, facilitating the co-localized delivery of both antigen and immune stimulating compounds necessary for eliciting a protective immune response in vivo. The goal of this project was to incorporate membrane protein antigens into NLPs and evaluate the efficacy of these formulations to protect against urinary tract infections in an animal model.