Promising ideas for preventing, diagnosing, and treating the most common vector-borne disease in America.

It’s the height of spring in the Northern Hemisphere, and for many people, that means spending more time outdoors. The longer days and warmer weather bring humans into closer contact with vector-borne diseases — infections transmitted by vectors such as mosquitoes, ticks, and fleas — which can include Zika virus, West Nile virus, dengue, malaria, plague, Rocky Mountain spotted fever, alpha-gal syndrome, and Lyme disease.

May is Lyme Disease Awareness Month, an opportunity to focus on the most common vector-borne disease in the United States. Many Americans live, work, and play in tick habitats — and the threat of Lyme disease looms large, especially now that a warming climate is increasing the geographic and seasonal distribution of ticks across the United States and environmental changes are making infectious diseases more dangerous around the world. Better prevention, diagnostic, and treatment options would bring greater peace of mind and improve public health. Current options are lacking — but thanks to an ongoing push for innovation, that may soon change.

What is Lyme disease?

The Centers for Disease Control and Prevention’s Lyme disease resource hub offers this description: “Lyme disease is caused by the bacterium Borrelia burgdorferi and rarely, Borrelia mayonii. It is transmitted to humans through the bite of infected blacklegged ticks. Typical symptoms include fever, headache, fatigue, and a characteristic skin rash called erythema migrans. If left untreated, infection can spread to joints, the heart, and the nervous system.”

Lyme disease isn’t just an East Coast problem: Blacklegged ticks (also known as deer ticks) are common in wooded and grassy areas, and Lyme disease can be found throughout the United States and in more than 60 other countries.

Prevention

The CDC’s current recommendations for Lyme disease prevention are largely behavioral: Avoid tick habitats; if you do go outside, wear long sleeves and pants and check yourself for ticks after you come back inside. The CDC also recommends checking pets for ticks and treating dogs and cats with tick-prevention products.

Tick-killing pills
Of course, completely avoiding the outdoors isn’t a reasonable option for people who live and work in areas with high tick populations. What if, like dogs and cats, people could take a preventative pill to protect themselves from infection? That’s the goal for a new oral medication that recently posted promising results from a human clinical trial. Normally, a tick carrying B. burgdorferi can only transmit the bacteria after it’s attached for more than 24 hours; with this pill, which is effective for 30 days, the tick dies and drops off before it has a chance to spread the disease.

Vaccines
Even easier than a monthly pill, vaccines could provide lasting protection against infection. More than two decades ago, a Lyme disease vaccine called LYMErix was available for only a few years; a “perfect storm of dismissive public-health experts, conspiracy theories, a class-action lawsuit, and a lack of consumer demand drove it off the market.” But now, a new crop of vaccine candidates are progressing through clinical trials. VLA15, from Pfizer and Valneva, has enrolled volunteers in a Phase 3 trial, with data expected in 2025; if the study is successful, the companies would submit regulatory filings in the U.S. and Europe the following year. Last year, Moderna announced two mRNA vaccine candidates, and researchers at the University of Pennsylvania published preclinical research on an experimental mRNA vaccine that produced promising results in animal models.

Monoclonal antibodies
MassBiologics, part of the University of Massachusetts, is researching a preventative shot for Lyme disease that would use human monoclonal antibodies as pre-exposure prophylaxis (PrEP) for Lyme disease. Unlike a vaccine, Lyme PrEP “prevents infection by delivering a single, human anti-Lyme antibody, or blood protein, directly to a person rather than triggering their own immune system to make many antibodies as vaccines do. If a person’s blood contains the correct antibody against the bacteria, the antibody can kill Borrelia in the tick’s gut before the bacteria has a chance to travel to the person.” The shot is immediately effective, but doesn’t last as long as a vaccine. Clinical trials are ongoing; MassBiologics hopes to make Lyme PrEP available by 2025.

Diagnosis

Each year in the United States, nearly half a million people are diagnosed with Lyme disease, but the true number of infections is unknown. The current diagnostic process is limited; it relies on a characteristic bulls-eye skin rash called erythema migrans or the CDC-recommended two-tiered antibody testing algorithm. Up to 30% of patients never present the rash, and it’s difficult to identify on darker skin, so clinicians sometimes misdiagnose patients of color. The two-tier antibody testing system — originally developed in 1994 for disease surveillance, not as a stand-alone diagnostic test — relies on the presence of antibodies and can only be used accurately four to six weeks after infection.

Diagnostic tests for active infection
There is currently no FDA-cleared test for active Lyme disease infection. Scientists have described the genome of Lyme disease-causing spirochetes as the most complex of all bacteria, and developing direct diagnostic tests is extremely difficult. The LymeX Diagnostics Prize, a $10+ million competition designed and produced by Luminary Labs on behalf of the U.S. Department of Health and Human Services and the Steven & Alexandra Cohen Foundation, is accelerating the development of Lyme disease diagnostics. Six teams have advanced to Phase 3 of the competition and are currently planning clinical performance studies for validating their proposed solutions. Over the next four months, the teams will have access to webinar modules, mentorship, and networking opportunities. The goal of the multiphase competition is to nurture the development of diagnostics toward Food and Drug Administration review.

Treatment

For those who receive an early diagnosis, the National Institutes of Health says a short course of antibiotics cures the majority of cases, with more complicated cases requiring three to four weeks of antibiotic therapy. (Of course, without diagnostics for active infections, cautious clinicians are apt to overprescribe antibiotics for potential Lyme disease cases, which may contribute to larger antimicrobial resistance problems.) Researchers are still trying to find an effective treatment for post-treatment Lyme disease syndrome (PTLDS), sometimes called chronic Lyme disease or persistent Lyme disease.

Novel antibiotics and anti-inflammatory treatments
Northeastern University has developed an experimental antibiotic treatment, hygromycin A, that specifically targets spirochetes including B. burgdorferi. Human trials are beginning this spring in Australia, with results anticipated later this year. Another team of researchers is studying how inhibiting fibroblast growth factor receptors (FGFRs), parts of a cell that help regulate key biological processes, may reduce brain inflammation and cell death associated with some Lyme disease cases where symptoms continue after antibiotic treatments.

Genomic and metabolic research
Tufts University has developed a genome-scale metabolic model of B. burgdorferi, and has used this “subway map” of key metabolic activities to identify compounds that could selectively target the disease-causing bacteria. Harvard University has conducted whole-genome sequencing on hundreds of samples of B. burgdorferi, shedding new light on the variability of symptoms and experiences — as well as potential strategies for diagnosis, treatment, and prevention.

Understanding the body’s response
A study funded by the Bay Area Lyme Foundation found that P66, a known surface protein in B. burgdorferi, can inhibit an important portion of the body’s immune response by sending a “don’t eat me” signal — which has also been found in some cancers. Researchers and funders are interested in the similarities and connections between Lyme disease and other conditions, including COVID-19. The University of California San Diego recently received a $1 million grant from the Steven & Alexandra Cohen Foundation to study tissue samples from patients with chronic and persistent conditions such as long COVID, relapsed Lyme disease, and chronic fatigue syndrome.

There’s no shortage of activity and innovation in Lyme disease research and development — and no better time to advance new ideas and promising solutions. Earlier this year, the U.S. Department of Health and Human Services released the National Public Health Strategy to Prevent and Control Vector-Borne Diseases in People, a collaboration with 17 federal departments and agencies, to continue accelerating patient-centered advancements through the use of strategic public-private partnerships and partner engagement. On May 23, CDC and HHS will host a public webinar to share information on the national strategy and a newly released multiyear plan: Learn more and join the livestream.