DEVELOPMENT OF CHIMERIC ANTIGENS FOR THE DETECTION AND PREVENTION OF EHRLICHIOSIS

Ehrlichiosis is a significant tick-borne zoonotic disease affecting both humans and companion animals, with increasing prevalence across the United States. Despite its public health importance, no effective vaccine exists for Ehrlichia, and current diagnostic methods remain limited by sensitivity, specificity, and accessibility challenges. This study explores innovative approaches to address these gaps by identifying, testing, and optimizing antigenic targets for vaccine and diagnostic development. Immunoprecipitation and LC-MS/MS analyses identified over 50 candidate antigens from Ehrlichia chaffeensis and Ehrlichia canis. Focused evaluation revealed that outer membrane proteins, including P28, P30, and Omp-1C, demonstrated robust immunogenicity and infection-blocking efficacy. A chimeric vaccine construct, HVR1-CHI, incorporating hypervariable regions from multiple Ehrlichia strains, exhibited superior performance, achieving up to 97-100% infection blocking in vitro. Furthermore, HVR1-CHI was successfully co-administered with chimeric Lyme vaccinogens Chv2M and BAF, supporting its potential integration into a multi-pathogen vaccine formulation. Chimeric constructs incorporating immunodominant regions of TRP47, TRP36, and Omp-1H were developed for diagnostics to improve sensitivity and specificity across diverse Ehrlichia species. Additionally, the importance of evaluating diagnostic specificity through multifaceted serum panel characterizations was emphasized, given the limitations of current diagnostic standards. Future directions include in vivo validation of vaccine efficacy using animal models, refinement of diagnostic tools for broader applicability, and detailed investigation of vaccine mechanisms to guide next-generation designs. By addressing critical challenges in preventing and detecting Ehrlichiosis, this work provides a foundation for advancing tick-borne disease management and mitigating its impact on human and animal health.