Center for Biologically Inspired Nano-scaffolds for Mitigating Chlamydia trachomatis Pathogenesis

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Abstract In order to address the critical need for a Chlamydia trachomatis vaccine, we propose to establish the NIH funded Sexually Transferred Infectious “Cooperative Research Center for NanoScaffold-Based Chlamydia trachomatis Vaccines.”, which is a collaborative center between LLNL, UCI and UCD. The Center is composed of scientifically diverse synergistic teams, which will be dedicated to developing new capabilities for expanding the application of nano-formulated vaccine technologies for mitigating health effects associated with Chlamydia trachomatis. Chlamydia trachomatis (Ct)is the most common bacterial sexually transmitted infection (STI), affecting over 130 million people every year, and is the most common cause of preventable blindness worldwide. The pressing public health need for a vaccine to prevent diseases caused by Ct is clear. Despite considerable efforts to develop a chlamydial vaccine, none have been forthcoming. While studies have shown that immunization with the Ct major outer membrane protein (MOMP) can induce significant protection, formulation and delivery of MOMP-related vaccines remains a major hurdle. This Center will focus on developing and testing a safe and efficacious Ct vaccine that overcomes the limitations of current efforts using LLNL nanolipoprotein particle (NLP) technology. NLPs are 10-25 nm disc we can engineer that will provide a unique path forward presenting functional Ct antigens as well as a novel tool for delivery of nucleic acids. We will evaluate two different types of nano-formulations with different delivery techniques, while validating an idealized mouse challenge model for Ct. Establishing this Cooperative Research Center (CRC) will further integrate LLNL's NLP-based nanotechnology with development of subunit vaccines and nucleic acid delivery, enabling us to accelerate the generation of a safe and efficacious Ct vaccine. The Center's efforts will include three research projects, which will tackle diverse approaches to vaccine development: § Project 1 will develop subunit vaccines based on serovar-specific forms of MOMP, as well as include polymorphic proteins, presented in nanolipoproteins. § Project 2 will demonstrate nanolipoprotein delivery of nucleic acid–encoded vaccines. § Project 3 will validate serovar-specific responses in mouse models, enabling us to refine, possibly combine, and apply formulations developed in Projects 1 and 2. The research projects will be supported by the Administrative Core and three scientific cores: 1) Bioinformatics and Statistics, 2) Protein Production and Characterization, and 3) Immunology. Overall, this CRC represents a unique approach to the development of vaccines against sexually transmitted infections (STIs) caused by Ct by establishing synergistic collaborations between experts in Ct and infectious disease with experts in structural biology and nanotechnology. Importantly, the proposed technology platform will form the basis for eradicating multiple infectious disease for which no vaccine is currently available.