Lyme disease diagnostics cleared by the Food and Drug Administration (FDA) rely on a long-lasting protein antibody—but could a short-lived lipid antibody provide a new way to diagnose infection? Building upon decades of research into Lyme disease, Tufts University launched the Tufts University Lyme Disease Initiative in 2019 with a clear mission: eradicate Lyme disease by 2030. Now, the team is one of 10 Phase 1 winners that have advanced to Phase 2 of the LymeX Diagnostics Prize, a prize competition to accelerate the development of Lyme disease diagnostics.

Through September 2023, the Phase 2 cohort is participating in a virtual accelerator designed to help them refine their concepts for detecting active Lyme disease infections in people. The goal of the multiphase LymeX Innovation Accelerator (LymeX) competition is to nurture the development of diagnostics toward FDA review.

We spoke with Tufts University’s Lyme Disease Initiative Director for Translational Research Dr. Peter Gwynne to understand how the team is translating antibody research from other infectious diseases such as syphilis, looking ahead to future work in Lyme disease, and considering the potential to use short-lived lipid antibodies for testing in other diseases—including long COVID.

Tufts University has a long history of studying Lyme disease. What led you personally to begin your research, particularly in diagnostics?
Gwynne: “For me personally it was intellectual—it’s a weird bacteria. Once I’d started doing the work, I had moved out to Boston, where everyone you meet has an uncle or a cousin who has had Lyme disease. You realize what a big problem it is; it exists in the U.K. where I’m from, but it’s not a huge public health crisis in the same way as it is here. You realize there are all these black holes in terms of management, diagnosis, and treatment. So it’s really exciting that you can do interesting science, but also there are still improvements to be made and a need for translational work.

The current tests are really good at telling if someone’s got Lyme disease—with the caveats around current antibody testing—but weirdly, what they’re less good at is telling if someone hasn’t got Lyme disease. You stay positive after you’ve been treated. That has a huge impact on everyone, not just on the people who get treatment and then don’t recover, but also on the people who get treatment and do recover. You still want to be able to point at something and say it’s definitely gone away. 

That’s what really surprised me when I started looking into the diagnostics—you don’t have anything that gives you the all-clear. We’re really interested in making the first diagnosis. But I think we also have a really good shot at a test that can give people the all-clear.”

While your diagnostic concept relies on antibodies, it’s significantly different from current testing. What does your test look at, and how do you hope patients and providers will use this test?
Gwynne: “We’re not trying to reinvent the wheel in terms of the technique and the assay and the system—we’re looking at what has been successful for other diseases. In particular, we’re looking at syphilis as a model. Syphilis has a measure that shows the treatment is working or not working. The unique aspect of our concept is it could help track people as they recover and offer that peace of mind.

Our research found a new set of antibodies which haven’t been described before in Lyme disease, but which are similar to the ones they use for syphilis tests and sort of behave in the same way as they do in syphilis. The current antibodies used in testing are protein antibodies, and they’re long-lived. Obviously that makes them a bad diagnostic test because you can’t tell if it’s a new infection or an infection from 30 years ago. 

What we are looking for is a different type of antibody that gets strongly induced in the middle of an infection, but then declines quickly. These are targeted to lipids in fat molecules, which make up the cell membrane in both bacteria and humans. They have a very strong primary induction, but then the antibodies are produced by a different set of white blood cells. The end result is that you get a really strong primary antibody response, but you don’t get the memory. So the antibodies tail off—they have a short half life because they’re not being constantly produced. The antibodies might be useful in the initial stages of an infection, but then you don’t want them hanging around for ages because they are going to start signaling to your body to attack itself. As part of our work, we’re testing for these antibodies in a bunch of samples from people with all kinds of different diseases. They’re pretty specific, but not super specific to Lyme disease, so we think these antibodies may be induced by all kinds of different diseases to some extent.

What we’re looking at is having an initial diagnosis and then adding our test after that as a tool in the disease management pipeline. So if you get treatment, you presumably go back to your doctor a month later. At that point they can do the clinical workup, but they would also get a diagnostic test with an antibody number. And in the ideal situation, the number keeps going down. But for people who aren’t getting better and the antibody titer is staying high, maybe it’s just a marker of disease. Then you’ve got some information that informs treatment.”

Through a range of monetary and non-monetary resources, the LymeX Diagnostics Prize is incentivizing transformative partnerships and catalyzing additional investment. How has participating in the prize competition impacted your team’s work?
Gwynne: “This was a project that we’d already been working on a relatively small scale. The LymeX Diagnostics Prize really pushed us into developing the next stage and starting to think about going through the FDA and setting up a real translational team rather than a research team. It is something that I’ve always been interested in, in principle, but is not what’s normally funded. 

In traditional academic labs, it’s hard to find opportunities to do translational research [because traditional funding sources like the NIH are focused on funding basic science]. There are really no prizes for doing something useful. The project and the team came together around the LymeX Diagnostics Prize because finally, there’s a natural reason to start thinking about translation at work and building those networks of clinicians, tech development people, and people who can do the intellectual property. 

The LymeX Diagnostics Prize gives all of us the impetus. It’s certainly given me personal justification to spend more time thinking about the translational work. How do we put this together into a package that would be usable in a hospital? The nuts and bolts of actually making a device or a test that you wouldn’t normally get the opportunity to do. Otherwise the last slide of your talk is you saying, ’Oh, we did this basic science, and then in theory someone could make a diagnostic test’ and then you don’t do it. 

And it’s all doable. What I’ve found is that it’s all things that you can do, it’s just not the things that universities traditionally think of. So the LymeX Diagnostics Prize has justified spending a whole load of my time to actually do the stuff that we wouldn’t normally do, which is interesting. It’s fun. Everyone started studying science because they want to be doing useful stuff, they want to be impacting clinical care and impacting real people.”

Your team’s participation in the LymeX Diagnostics Prize is part of Tuft University’s larger investment in Lyme disease research. What comes next?
Gwynne: “Tufts has a particular connection with Lyme disease. A bunch of the super early work, back to the discovery of the disease, was done at Tufts. It was long before my time, but Tufts was involved in the vaccine development, in the development of the initial diagnostic test, treatment regimes, all kinds of stuff. 

We’re building that into a kind of center for Lyme disease with the Tuft Lyme Disease Initiative to pull together all of that expertise. This project is the first funded concrete piece of research with a clear end point from the Tufts Lyme Disease Initiative. We’re really excited to take the team and see what it can do. A network of people who are clinicians and basic science and ecologists and all of the people hitting all of the different aspects of Lyme is a really great team.”

As you noted, this antibody is not unique to Lyme disease. How could your research be applied to other infectious diseases?
Gwynne: “What’s really interesting is that we’re seeing some overlap in the production of these antibodies and diseases that are kind of lookalike conditions with Lyme disease. We’re seeing that lupus and multiple sclerosis produce a similar kind of antibody, which is really interesting because it’s possible that these antibodies are a marker and correlate with disease. And if they correlate with disease, maybe they have a role in causing the actual disease itself. So we’re really focused on whether these antibodies are correlating with disease because they’re playing a role in actually triggering the disease. What’s particularly interesting with the kind of long-term symptoms that some people describe is that those symptoms do look a lot like some autoimmune diseases.

Other people have also reported similar kinds of antibodies showing up in long COVID. Again, it’s part of that idea that the antibodies seem to correlate with all kinds of diseases. I’m not a clinician and I never worked with COVID-19 patients, but long COVID has a lot of overlap with long Lyme.”

Looking ahead: Expert judging panel to convene in October 2023

Following the accelerator, the cohort will submit concept papers that detail solution refinement, clinical and patient input, and a roadmap from lab to market. The competition judging panel—composed of experts across biology, clinical and technology translation, patient experience and advocacy, diagnostic science and technology, exponential innovation, and ethics—will evaluate eligible submissions according to official Phase 2 evaluation criteria. Based on the judges’ evaluations, the panel will recommend up to five Phase 2 winners of the LymeX Diagnostics Prize.

To receive all Phase 2 updates, subscribe to the LymeX Diagnostics Prize newsletter and follow @Lyme_X on Twitter.