Peptide-vaccine development against Lyme disease Supplement

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Project Summary Lyme disease is an endemic tick-borne disease associated with debilitating manifestations such as arthritis, muscle pain, carditis, meningitis, and encephalomyelitis. Despite extensive efforts in the field, there is still no vaccine for the prevention of this infection available for human use. To address this problem, our laboratory has developed novel methodologies to identify antigens relevant during bacterial infection in ticks and mammals and design peptide antigens based on extracellular and conserved regions of these proteins. Through the work proposed in the parent application, we are selecting and evaluating outer-membrane proteins expressed in various phases of the enzootic cycle of B. burgdorferi as vaccine antigens against Lyme disease. This is currently performed using peptide and recombinant protein-based vaccines. In this supplement, we propose to expand vaccine formulations to the mRNA vaccine platform. We have secured partners that will generate mRNA constructs encoding the antigens of interest and encase them in world class clinical grade lipid nanoparticles. We will first validate the mRNA technology for in vitro and in vivo expression and immunogenicity, and perform head-to-head comparisons with the peptide and recombinant formulations. We will use veterinary Lyme vaccines for comparison. At the conclusion of this work, we will have evaluated a novel platform for Lyme vaccine development and generated essential pre-clinical data to enable transition to clinical studies for the development of a vaccine against Lyme disease in humans.