Researchers at the Tufts Lyme Disease Initiative recently received grants totaling more than $7 million to build on an already impressive array of discoveries that Tufts' teams have made to combat tick-borne diseases.

While Lyme disease can often be successfully treated with antibiotics, 10-20% of patients experience persistent fatigue, joint pain, and mental impairments that last months or years. For some, it is never clear whether symptoms signal persistent infection, reinfection, or malfunction by the body's immune system.

Researchers Linden Hu, Peter Gwynne, and colleagues will use grants from the Department of Defense (DoD) and National Institutes of Health (NIH) totaling $4,555,445 to understand the underlying causes of chronic Lyme disease and conduct a large test of a promising screening tool to diagnose Lyme disease sooner, show when people are cured of an initial infection, and diagnose reinfection. Hu is the Paul and Elaine Chervinsky Professor of Immunology and a professor of molecular biology and microbiology at Tufts University School of Medicine. Gwynne is a research assistant professor in molecular biology and microbiology at the School of Medicine.

Along with Samuel Telford III, a professor in the Department of Infectious Disease and Global Health at Cummings School of Veterinary Medicine, Hu and other colleagues also received an $885,000 grant from Tarsus Pharmaceuticals to help develop an oral drug that could be used to kill ticks that are feeding on humans, thereby preventing transmission of Lyme disease.

Klemen Strle, a research assistant professor in molecular biology and microbiology at the School of Medicine, will use a $475,000 grant from the Global Lyme Alliance to study whether abnormally high levels of the immune system component interferon-alpha (IFN-alpha) signals an increased likelihood of developing the long-term effects of Lyme. Elevated IFN-alpha levels are also seen in people with long COVID. This research could lead to new screening tools and treatments for those with persistent Lyme, long COVID, or other diseases with similar symptoms. Anti-IFN-alpha therapies are already used in autoimmune conditions such as lupus.

Tanja Petnicki-Ocwieja, a research assistant professor in molecular biology and microbiology at the School of Medicine, is studying another facet of an altered immune response that may trigger persistent symptoms. Like Strle, her efforts may help scientists better understand both chronic Lyme and long COVID. Petnicki-Ocwieja's $200,000 grant from the Global Lyme Alliance focuses on innate immune memory, also known as trained immunity, which alerts the immune system to a foreign invader and helps the immune system quickly respond to intruders that it believes could be harmful. The new research will characterize whether and how an innate immune memory malfunction may cause chronic Lyme symptoms. Discoveries could lead to new tests to detect those susceptible to persistent Lyme caused by this mechanism.

Jeff Bourgeois, a postdoctoral scholar in molecular biology and microbiology at the School of Medicine, will use a $210,372 grant from the NIH to study interactions between the Lyme disease bacterium and one of its natural hosts, the Peromyscus leucopus mouse, which does not show symptoms of infection despite remaining infected for life. By better understanding the bacteria's life cycle, he hopes to identify drug targets in rodents that could prevent spread of the bacteria and find ways to make humans respond more like the mice and avoid Lyme disease symptoms altogether.

Edouard Vannier, an assistant professor of medicine at the School of Medicine and in the Division of Geographic Medicine & Infectious Diseases at Tufts Medical Center, and his colleagues have received two grants from the NIH and the DoD totaling $1,048,885 for research to prevent another tick-borne disease, babesiosis. In one study, he and colleagues will test the ability of an anti-malarial drug, tafenoquine, to prevent babesiosis in mice. In limited human testing, tafenoquine has been effective in treating babesiosis. In a second study, they will test whether immunization with one of three potentially promising antigens protects young mice from infection, and whether protection is as strong in older mice. If successful, these studies could lay the groundwork for clinical trials to determine whether one or more of these antigens could prevent human disease.