Evaluation of multiple platforms for the formulation of a multivalent vaccine against Borrelia burgdorferi 3064

Abstract Description Lyme disease (LD), caused by Borrelia burgdorferi, leads to an estimated 476,000 cases annually in the U.S. Furthermore, the presence of nonspecific LD symptoms frequently results in misdiagnosis and delayed treatment. Although LYMErix® showed initial promise with an rOspA vaccine approach licensed in 1998, it was withdrawn in 2002, and no FDA-approved LD vaccine is currently available. Our long-term goal is to develop an immunogenic and efficacious multivalent vaccine against B. burgdorferi, with long lasting protection. Moreover, recombinant protein may not be the optimal vaccine delivery platform for LD vaccines given LYMErix’s incomplete protection and short-term duration, despite an extensive vaccination schedule. We hypothesize that alternative delivery platforms, such as fusion proteins, virus-like particles (VLP), and mRNA constructs, developed in our laboratory, will serve as better delivery platforms. Additionally, we propose to combine OspA with other immunogenic, conserved outer surface proteins (OSPs) expressed at different stages of infection. Our data suggests that in mice, VLP and EcoCRM-conjugated delivery platforms produce higher serological responses than recombinant protein alone. We have observed that antigen localization affects immunogenicity in mRNA vaccine formulations. In addition, we identified three different immunogenic OSPs. This research is crucial as it can influence platform decisions and antigen selection in the development of a LD vaccine. Funding Sources Supported by NIH 5R01AI152219-05 Topic Categories Vaccines and Immunotherapy (VAC)