Brissette Co-Investigator on 2 NIH Grants

Dr. Catherine Brissette, Associate Professor with the Department of Biomedical Sciences at UND's School of Medicine & Health Sciences, has the role of Co-Investigator on 2 National Institutes of Health (NIH) grants beginning this year.

Tick-borne pathogens cause more than 77% of the vector-borne disease cases in the US, with the annual reported cases more than doubling since 2004. Among these tick-borne diseases, Lyme disease (LD) is escalating, due in part to range expansion by the tick vector Ixodes scapularis. Although LD patients can be successfully treated by a course of oral antibiotics, a sizeable number of individuals continue to suffer long-term, debilitating sequelae, including pain, fatigue, cognitive dysfunction and other symptoms. With no vaccine available, clearly novel intervention strategies are needed.

One strategy to prevent LD is pre-exposure prophylaxis (PrEP). In a Phase I STTR (R41AI152954 awarded 7/17/20), Keith Wycoff (Planet Biotechnology, CA) Yi-Pin Lin (Wadsworth Center, NY) and Catherine Brissette (UND SMHS) will develop an innovative PrEP that turns the pathogen complement evasion system against itself. The complement system is a critical component of innate immune defense. Host cells are protected from complement attack by host complement regulatory proteins. The Lyme disease pathogen Borrelia burgdorferi produces outer surface proteins that recruit the soluble complement inhibitor Factor H (FH) to their surface to inactivate complement. A recombinant fusion protein combining domains of FH and immunoglobulin Fc (FH-Fc) will be tested against several tick-borne pathogens, including Lyme Borrelia. A PrEP based on FH-Fc has commercial potential, with the target market being individuals at high risk for LD.

Another approach to tackle LD is to eliminate the ticks that carry the pathogen. In a recently funded R21 (R21AI154045, awarded 8/25/20), Jefferson Vaughan (PI; UND) and Catherine Brissette (Co-I) propose to employ large-scale, strategic placement of treated bait to break the zoonotic transmission cycle of many tick-borne diseases including LD. Recently, a new class of systemic drugs, the isoxazolines, have been introduced into the veterinary market for flea-and-tick control in dogs and cats. These drugs can be administered orally, possess extremely low mammalian toxicity, and have long residual activity against a variety of tick species, including Ixodes scapularis. The overall goal of this R21 proposal is to test the efficacy of the available isoxazoline drugs against ticks in a controlled, laboratory setting using actual rodent reservoir species. This project will determine the feasibility and likelihood of success for a targeted deployment of rodent baits to suppress the spread of Lyme disease and other tick-borne zoonoses across the northern Great Plains.