Developing a Potent Broad-Spectrum Prophylactic for Tickborne Disease

The product we are developing, Fc3/SCR(19-20), is a protein of our own design that will be administered as a yearly shot to prevent two tick-borne diseases, Lyme Disease (LD) and Relapsing Fever (RF). Unlike vaccines, it does not depend on stimulating the immune system, and thus should be equally effective in both healthy and immunocompromised recipients. We have shown that Fc3/SCR(19-20), injected into mice, prior to exposure to infected ticks, reduces the transmission of LD bacteria to the treated mice. For yearly Fc3/SCR(19- 20) injections to become a practical strategy for preventing tick-borne diseases in people, we need to improve the bioavailability, safety and longevity of the protein in the body, so that it provides effective season-long protection at a lower dose. To achieve these three objectives, this project brings together two research groups, each with their own unique qualifications. Under the direction of the PI, Planet Biotechnology (PBI), using plants grown in an indoor facility, will produce multiple variants of Fc3/SCR(19-20), with the goal of enhancing bioavailability, safety and longevity of protection. PBI has pioneered methods for producing, purifying and improving the function of proteins like Fc3/SCR(19-20) using a plant transient expression system, including the first plant-produced antibody tested in clinical trials. A research group at the New York State Department of Health, led by Dr Yi-Pin Lin, will test the relative ability of these new Fc3/SCR(19-20) variants to kill LD and RF bacteria in vitro and to block transmission of LD bacteria into mice from infected ticks. They will also evaluate the pharmacokinetics and pharmacodynamics of Fc3/SCR(19-20) in mice, in order to determine the duration of protection. Ultimately, we aim to develop Fc3/SCR(19-20) as an FDA-approved drug, for annual administration as an injection, to provide protection against LD and RF through a full tick season. Untreated, these diseases can have significant long-term health consequences. We expect that widespread adoption of our preventive strategy would significantly improve the quality of life for anyone living or working in high LD or RF risk areas. Although our focus now is on prevention, it is possible that Fc3/SCR(19-20) could be effective as a treatment for LD as well. To achieve FDA marketing approval, Fc3/SCR(19-20) will need to go through all of the pre-clinical and clinical testing typical of a biotechnology-derived new drug. Assuming successful completion of all the aims of the proposed project, follow-on studies will determine the minimally effective dose in rhesus monkeys (to predict the effective dose in humans), evaluate the long-term safety of Fc3/SCR(19-20) in rats and monkeys, and undergo rigorous clinical testing. We project that Fc3/SCR(19-20) could be commercially available in 5-6 years. Fc3/SCR(19-20) targets (and blocks) a mechanism that LD and RF bacteria normally use to evade the host immune response, so development of bacterial resistance may be less likely than with a monoclonal antibody.