Yale Researchers Advance Work in Diagnosing and Preventing Tick-Borne Diseases

New research led by Yale School of Medicine (YSM) advances the goals of creating a diagnostic test and vaccines for tick-borne diseases. The study was published March 26 in Science Translational Medicine.

Ixodes scapularis, also known as the deer tick and black-legged tick, is the primary vector for several tick-borne diseases, including Lyme disease, babesiosis, anaplasmosis, and Powassan virus disease. Tick-borne diseases are a big and growing public health problem. Lyme disease alone infects 500,000 Americans annually, and warmer temperatures from climate change mean tick species are expanding beyond their traditional habitats.

The current research focuses on two challenges in preventing and diagnosing tick-borne diseases, said Erol Fikrig, MD, Waldemar Von Zedtwitz Professor of Medicine (Infectious Diseases) and professor of microbial pathogenesis at YSM, who led the research. Fikrig is also a professor of epidemiology (microbial diseases) at the Yale School of Public Health.

“We asked what targets we can recognize following a tick bite to develop tests to improve the diagnosis of tick-borne disease, and if we can use the immune response to those targets to develop an anti-tick vaccine,” he said.

To evade detection, ticks emit proteins that numb the bite site and suppress an immune response. Some animal species have developed tick resistance, which interferes with the ticks’ feeding and makes them detach. The team had heard from hikers, gardeners, and people studying and collecting ticks who thought they had developed a similar form of resistance.

This evidence of developed resistance seemed to mean a vaccine could be effective. But ticks secrete thousands of proteins, and figuring out which the human immune system recognizes has been a research challenge.

To help solve it, the researchers built what they call the I. scapularis rapid extracellular antigen monitoring, or IscREAM, library. The library is made up of yeast cells engineered to display each of the 3,000 possible I. scapularis antigens on their surfaces. For one step of this project, the researchers combined the yeast cells with serum from people with recent Lyme disease. The antigens the human antibodies attached to could be targets for a vaccine or a tick bite test.

“It’s a powerful way to map the immune response to a vast number of tick proteins all at once,” said Thomas Hart, a former Yale postdoctoral research fellow who led the work to create IscREAM. “Previous methods could only examine a handful of known proteins at a time or relied on crude mixtures of tick proteins, which left many potential targets unexplored."

Serum from 52 patients was tested. Serum from 33 people recognized at least one and an average of eight antigens per person, for a total of 177 antigens recognized.

Another aspect of the research confirmed what the team had heard anecdotally about human tick resistance. Serum from a volunteer who had reported resistance was transferred to guinea pigs, who then showed resistance.

The team also vaccinated guinea pigs with an mRNA vaccine encoding 25 antigens in tick cement, the substance ticks secrete to attach themselves to their hosts. Vaccinated guinea pigs showed signs of tick resistance.

Because the immune responses from the people with Lyme disease varied, more work will need to be done to determine which targets could be biomarkers for a tick bite, Fikrig said. But the mRNA vaccine results are encouraging, he said.

“An anti-tick vaccine based on the cement targets in this paper is promising, and I’m hopeful one will be available in the next five to 10 years,” he said.

The research reported in this news article was supported by the National Institutes of Health (awards R01AI126033, P01AI138949, U19AI089992, and 1S10OD030363-01A1). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This work was also supported by the Steven and Alexandra Cohen Foundation, the Howard Hughes Medical Institute Emerging Pathogens Initiative, Tito’s Handmade Vodka, VIDI, and the Netherlands Organisation for Health Research and Development.

Yale School of Medicine’s Department of Internal Medicine Section of Infectious Diseases engages in comprehensive and innovative patient care, research, and educational activities for a broad range of infectious diseases. Learn more at Infectious Diseases.