Sequencing-driven identification of immunotherapeutics for treatment of Lyme disease 4155

Abstract Description Lyme Disease (LD) is the number one tick-borne disease in the U.S., with an estimated incidence rate of at minimum 60,000 individuals each year. In the U.S., LD is caused by the gram-negative spirochete B. burgdorferi (Bb) and is transmitted to humans through bite of a Bb-infected Ixodes scapularis tick. Bb has many mechanisms in which it can persist and disseminate through the human host, highlighting the importance of early diagnosis and antibiotic treatment for avoidance of the potential long-term multisystem effects of LD. However, an estimated 14% of individuals present with symptoms of LD post-treatment. In addition, regardless of treatment, prior infection with Bb does not result in protection from future infections. This is due in part to Bb’s effects on the host immune response. Therefore, we hypothesized that Bb infected mice could be treated with immunotherapies that stimulate the innate and adaptive response to Bb. To identify targets for therapeutic treatment, we performed single-cell RNA sequencing on the lymph nodes of Bb-infected mice 14 days post challenge. Targets for immunotherapy treatment are then formulated as mRNA, allowing their effect on the immune response and pathogen clearance to be assessed. If effective, we hypothesize that immunotherapies could be combined with current antibiotic treatments, to help improve their therapeutic efficacy. Funding Sources Supported by NIH 5R01AI152219-05 Topic Categories Vaccines and Immunotherapy (VAC)