Proof-of-concept study for the development of next generation vaccines for tick-borne intracellular diseases 3171

Abstract Description Development of effective vaccines for tick-borne diseases (TBD) is crucial, as there are currently no licensed human vaccines. Most TBD vaccines under development are humoral (antibody-based). However, as many of these pathogens are intracellular, we expect cell-mediated immunity (CMI) is required. Indeed, current candidate vaccines for intracellular TBD microbes don’t provide heterologous protection, likely because the responses to extracellular antigens are humoral, which provides constant evolutionary pressure on these antigens to change. We hypothesize that intracellular virulence factors, which may be conserved between multiple pathogens, are appropriate candidate vaccine antigens for intracellular pathogens. Further, we believe TBD vaccine development for intracellular pathogens fails for a specific immunological reason: the tick bite (site of infection) induces local Th2 immunity, which can inhibit development of Tc1/Th1 vaccine responses. Using rickettsial antigens as proof-of-concept, we have rationally selected two novel candidate antigens for which there are no published Tc1 or Th1 epitopes. For this work, we use BALB/c mice, since they are more Th2-prone, and they can be infected by Rickettsia parkeri, the BSL2 mouse model of the human BSL3 pathogen, R. rickettsii. Here, we are identifying the H-2d-restricted (BALB/c-specific) immunodominant epitopes and performing an immunogenicity study using the candidate vaccine antigens delivered by multiple delivery systems. Funding Sources Supported by Virginia Commonwealth Research Board 221-01-22. Topic Categories Vaccines and Immunotherapy (VAC)