From mice to men: breaking the transmission cycle of Lyme disease

A tick bite during a walk in the woods or any bushy areas may have serious consequences if the tick is carrying Borrelia burgdorferi, the bacteria responsible for Lyme disease. The infection often results in a skin rash, fever, and headache. If left untreated, it can also spread to the heart and the nervous system, and some patients may develop arthritis.

B. burgdorferi expresses outer surface proteins (Osp) that are key to transmission between hosts. Scientists have used some of them as antigens to develop vaccines to prevent Lyme disease. In the 1990s, for instance, researchers developed an OspA-based vaccine that successfully completed clinical trials. Although the FDA approved the vaccine in 1998, some reports of adverse reactions, including arthritis, raised concerns among the population (1). While there was not enough evidence of a causal relationship between the vaccine and those adverse effects, the media coverage of the vaccine’s risks and its reduced sales led the company to withdraw it from the market (2).

A person wearing glasses, a white (blouse) and a blue scarf is using a pipette in a lab background

Maria Gomes-Solecki and her colleagues developed an oral vaccine for mice to prevent transmission of Lyme disease to humans.

Credit: Jialei Jia, UTHSC Communications and Marketing

These events 20 years ago prompted Maria Gomes-Solecki, a Lyme disease vaccine researcher at the University of Tennessee Health Science Center, who was part of the team that developed that vaccine, to try something different. She used all of the knowledge on OspA to instead develop a vaccine for mice, the major reservoir animal for B. burgdorferi in nature, with the goal of breaking the transmission cycle between hosts. After nearly two decades working on that project, last year, the USDA conditionally approved this oral vaccine for mice, meaning that it will soon head to the market.

How did you become interested in studying Lyme disease?

When I secured my degree in veterinary medicine at the University of Lisbon, I first explored the clinical aspect of it. However, I soon transitioned to research. Given my background in veterinary medicine, I have been mostly interested in developing vaccines and diagnostic assays. I first focused on leishmaniasis because that disease caused significant concern among dogs at that time in Portugal. When I moved to the US to work at Stony Brook University in the mid-1990s, I realized that Lyme disease was the most important issue to tackle there.

Why is the OspA a good antigen for developing vaccines against Lyme disease?

Borrelia transits between the host — a mouse, a dog, or a person — and the tick and then back to another host. OspA expresses on the surface of Borrelia, mostly as the bacteria transit through the tick. If we vaccinate people or mice with OspA, they will produce antibodies targeting the protein. When the tick ingests the blood, these antibodies will neutralize Borrelia inside of the tick, rendering the bacteria unable to travel from the tick to the host. We call this a transmission blocking vaccine.

This is not achievable if the vaccine is based on other Osp proteins, such as OspC, which express on Borrelia as it transits into the host. In that case, the host will produce antibodies to OspC that neutralize the protein once it is inside the host, but it is difficult to prevent infection at that stage. This is similar to the vaccines for COVID-19. In contrast, OspA-based vaccines prevent transmission from the tick to the host; that’s why it is so efficient. It really is beautiful the way it works.

How did you conceive the idea of developing a vaccine for rodents?

I remember very well the day we read the reports on the potential side effects of the vaccine for humans. I recall sitting with my colleagues. We concluded that while the vaccine had been approved, its success in the market was now uncertain. That’s when we started to think of alternative paths.

I decided to continue working on OspA-based vaccines. I had been doing research for enough time to understand that OspA is the best candidate that we have, and there’s not going to be another one any time soon. I thought that we could still use it to tackle the disease, albeit not directly in people. We could use OspA to break the transmission cycle of Borrelia by vaccinating mice.

How was the process from developing the vaccine in the lab to obtaining approval from the USDA?

The development process was relatively straightforward; all I had to do was to modify the intramuscular injection to oral delivery. I conducted those first experiments around 2002.

OspA-based vaccines prevent transmission from the tick to the host; that’s why it is so efficient.
- Maria Gomes-Solecki, University of Tennessee Health Science Center

Once we saw that it worked, we tested the oral vaccine in a controlled environment in the wild. By 2012, we knew that the oral vaccine for mice worked the way that we intended (3). At that point, together with some colleagues, I cofounded US Biologic, Inc., based in Memphis, so that we could license this technology to the company, and its team could work to get the approval from the USDA.

The USDA granted provisional approval to our vaccine in 2023. It was a great accomplishment.

How will people make use of this vaccine?

People spray the vaccine on the outside of dry mouse food. They can deliver these pellets in various ways. For instance, we have considered arranging them in carousels that can be placed in grassy areas. Mice can take one pellet and run with it without being trapped. It smells like food, except that it doesn’t have much protein, so mice will remain hungry and go on foraging as they usually do. That’s how they get vaccinated.

There are some potential strategies for selling these pellets with the vaccine. People may buy them to distribute them in their backyards, or workers maintaining lawns can place them around. Another option is bulk sales to state or local park authorities for trail distribution.

In the end, mice vaccinated in all of those public or private areas will help block transmission of Borrelia burgdorferi from the tick to the hosts.

What else are you working on these days?

I chose to shift my focus away from intramuscular vaccines. I didn’t want to follow that same path since there are plenty of people working in that area. Instead, I’ve mostly worked on approaches that target mucosal immunity, which includes oral and intranasal vaccines. An advantage of these vaccines is that individuals can self-administer them.

We’re now working on an intranasal vaccine for humans that is also a based in OspA (4). In contrast with other human Lyme disease vaccines currently under testing, this one requires only two inoculations: prime and boost. We still need to do further work in mice to define the best scheme for delivering the vaccine before moving into clinical trials.