After 25 Years Studying Lyme Disease, UToledo Researcher Gets His Biggest Shot at a Developing a Vaccine

After 25 Years Studying Lyme Disease, UToledo Researcher Gets His Biggest Shot at a Developing a Vaccine

Dr. Mark Wooten grew up raising cattle in rural Arkansas, wandered into bacteriology in college, and made a bet early in his career that Lyme disease was going to become a major public health problem.

Twenty-five years later, working out of The University of Toledo, he's still collecting on that bet.

Wooten, a professor in the Department of Medical Microbiology and Immunology in the College of Medicine and Life Sciences, has received a five-year, $3.7 million award from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health. The grant will help him continue developing an unconventional Lyme disease vaccine built around something he noticed while watching bacteria move inside living tissue under a microscope.

There is currently no Lyme disease vaccine available in the United States. The last one, LYMErix, was pulled from the market in 2002. Meanwhile, the CDC estimates approximately 476,000 people may be diagnosed with Lyme disease each year in the United States, and the tick populations that carry it have been steadily expanding their range, including into Ohio.

Lyme disease is caused by Borrelia burgdorferi, a bacterium that spends its entire life inside either the tick that carries it or the animal or human it infects.

"It's what's called a spirochete. It looks and moves like a snake," Wooten said. "It can't live outside of a host; it has to be inside either the tick that transmits it or some reservoir species like mice."

What makes the disease so damaging is what happens after infection takes hold. The bacteria spread through the body, triggering inflammation wherever they reach a critical threshold: Lyme arthritis in a joint, Lyme carditis in the heart, and neurological symptoms and brain fog when they reach the brain.

"Antibiotics can clear it, but there's damage already done to your heart or your brain that can cause chronic disease," Wooten said. "That's why there's a push for vaccines to keep it from ever being established."

Wooten's vaccine takes an unusual approach. While using advanced microscopy to study how the bacteria navigate through tissue, his team engineered a strain that could only move forward. Unable to reverse when they hit a dead end, the bacteria became trapped, stopped moving and were eventually cleared by the immune system.

"We engineered this one and it can't go in reverse, it can only go forward," Wooten said. "And so, because of that, they could last about three days, but eventually they're blocked. Once they stop moving, they can be seen by the immune system."

What Wooten calls a "crippled" version of the bacteria triggers a full immune response before being cleared from the body. It's the same principle behind attenuated vaccines like those for measles and chickenpox, in which a weakened form of a pathogen trains the immune system without causing disease. In previous studies funded by the U.S. Department of Defense, the strain produced an immune response as rich and complex as a natural infection, protected mice for up to a year after immunization and was cleared safely even in animals with severely compromised immune systems.

UToledo filed a provisional patent application for the approach in December 2025, with research assistant John Presloid named as co-inventor. A decision on converting it to a full utility or international patent application is expected by the end of the year, a step that would position the technology for potential licensing or commercial partnerships.

The new grant will allow Wooten's team to refine the attenuated vaccine by testing different doses, timing schedules and immune-boosting additives called adjuvants. They'll also work to identify which proteins on the bacteria's surface are most responsible for triggering protective immunity, with the goal of building a cleaner recombinant vaccine containing just those key proteins.

"Some people don't want attenuated bacteria in their body," Wooten said. "But if I can identify a handful of candidates that promote protective immunity, I can make a cocktail with two or three recombinant proteins. It'll be cleaner."

By the end of the grant, Wooten hopes to have at least one candidate ready to attract pharmaceutical interest and move toward clinical development.

"My hope is at the end of five years, we'll have either an attenuated vaccine that would be close enough to good that pharma would be interested, or a mix of individual recombinant proteins that pharma would probably be more interested in," he said.

The grant will also expand Wooten's lab, funding research associates, postdoctoral researchers and students and continuing his 25-year track record of training infectious disease scientists at UToledo.