Why Don’t We Have A Vaccine For Lyme Disease?

FLORA LICHTMAN: This is Science Friday. I’m Flora Lichtman.

It is peak tick in some parts of the country. And data suggests it may be the worst tick season in years. Fordham’s Tick Index even rates concrete jungle New York City as high-risk at the moment.

Of course, the big concern is diseases ticks carry, including Lyme disease. Without quick treatment, Lyme disease can be debilitating, spreading to the joints, muscles, and nervous system, prompting arthritis symptoms with a side of brain fog.

So here is the question on my mind. Why is there no vaccine for Lyme disease? There’s a Lyme disease vaccine for dogs. We’ve had it for years. Why not one for people?

Here to take a bite out of this question is Dr. Linden Hu, an immunologist and Lyme disease specialist at Tufts Medical School in Boston, Massachusetts. Linden, welcome to Science Friday.

LINDEN HU: Oh, thanks so much. Glad to be here.

FLORA LICHTMAN: Why is this year so bad for ticks?

LINDEN HU: I’d say that’s really hard to say. There are probably lots of different factors involved. But things like how cold the winter was, how much snow cover there was– so typically, more snow has an insulating effect. So it helps keep the ticks alive a little bit better. Very cold weather will kill the ticks.

Once we get out of winter, one of the big things that affects it is how much moisture there is. Ticks survive heat pretty well. But they do not survive lack of moisture. So when we have a dry spell, it often will wipe out tick populations. So even seasons that start out very robust with lots of ticks– if we hit a dry spell, the tick populations will crash.

FLORA LICHTMAN: Let’s talk a little bit about Lyme disease. It’s a bacteria. But what does it do in the body?

LINDEN HU: So it’s actually a really wimpy bacteria, in a lot of ways. It’s very dependent on its environment to survive. And it can’t survive outside a tick or mammalian host. So typically, what happens is an infected tick will bite you or bite an animal. Most of how this is maintained in the wild is through small rodents and passed between ticks and rodents. And we’re kind of incidental to all of this. We get accidentally infected.

But when it passes to a human, it usually starts at the site of the tick bite. The bacteria exit the tick and enter into the skin. And it starts to replicate in the skin. From there, it goes pretty quickly to other parts of the body. It can go to other skin sites. It can go to the brain. It can go to the heart. It can go to the central nervous system.

FLORA LICHTMAN: And I know it can feel like arthritis. Does that mean it’s going to the joints, too?

LINDEN HU: Yeah. So true arthritis– it does go to the joints. True arthritis, in medical parlance, is inflammation. Very often in early disease, people will get joint aches. And that may not necessarily be the bacteria itself. That may be part of the illness with fevers and other things like that. But it definitely does get to the joints– tends to get to the joints and cause true arthritis a little bit on the later side. So it’s not one of the first manifestations, but something that happens a month or so into the infection.

FLORA LICHTMAN: When was Lyme disease first identified?

LINDEN HU: So it was identified here in the United States in the 1980s, where they saw an unusual cluster of juvenile arthritis in children in Old Lyme, Connecticut.

FLORA LICHTMAN: That surprises me. And I’m wondering, why the ’80s? Was it not here before, or was it that tick populations have changed? What happened?

LINDEN HU: So probably a combination of a lot of things. A very similar disease was present in Europe and first identified in the 1940s. And it’s probably been there even longer than that. And I think the best guess that most people have is that it came over from Europe, established itself in certain areas. But then it takes a while to get enough ticks infected to pass it in the rodent population so that people start to get infected. And then you need enough people infected so that we notice that there’s a new disease going on.

FLORA LICHTMAN: I want to get to my personal burning question. There is a vaccine against Lyme for dogs. Why is there not one for humans?

LINDEN HU: So there was one for humans. And it actually is very similar. It came out before the one for dogs. And it’s actually very similar to the one for dogs. The reasons for why it’s no longer available for humans are complex.

When it first came out, it was first approved in 1998. The incidence of Lyme disease was a lot lower than it is now. And the recommendations for use were pretty limited. So it wasn’t very widely used at that point.

And then there came reports that linked it, potentially, to the development of an autoimmune arthritis. And then when that came out, as they were sorting it out, that really tanked the sales and it was pulled from the market. The approval was never withdrawn. But it was pulled from the market because of low sales.

FLORA LICHTMAN: And did it cause arthritis?

LINDEN HU: So subsequent studies have shown that it really does not cause arthritis. It was a theoretical risk. And the original studies were based on studies from cells from one patient and, subsequently, have not proven to be the case.

FLORA LICHTMAN: Where are we in development with new Lyme vaccines?

LINDEN HU: So there is a vaccine very similar to the original vaccine, although they’ve engineered out the part that might have caused autoimmune arthritis out of an abundance of caution, that is in current phase III trials. And the initial reports from the phase II look very promising.

FLORA LICHTMAN: When might we see it in the market?

LINDEN HU: I think the hopes are that they’ll finish data collection in– sometime in early 2026 and then hopefully, if the data looks good, bring it before the FDA in 2027– so probably another couple of years before we have a vaccine available.

FLORA LICHTMAN: You work in this vaccine world. Are people optimistic that a new vaccine will be approved under this administration?

LINDEN HU: I certainly hope so. I think the politics of what’s going on may affect how well a vaccine is taking up by the public and seen. There are certainly risks there. But I think given the long history of similar types of vaccines for Lyme disease, as well as the use in animals– hopefully provides enough of a safety window to make people feel comfortable. Obviously, I’m not on the FDA panel that reviews it. But I would hope that it would get approved. But then the uptake on the back end is questionable.

FLORA LICHTMAN: Right. That’s a whole other piece of it. How do these vaccines work? Do they work like the vaccines we’re familiar with, where you introduce the bacteria and then you’re– you have antibodies to that bacteria?

LINDEN HU: Yeah. So I’m going to geek out here for a second because it’s a really–

FLORA LICHTMAN: Please, yes.

LINDEN HU: It’s a really interesting vaccine. It’s a protein vaccine against protein that the bacteria make called outer surface protein A. But the way that this protein gets expressed– it’s only expressed by the bacteria when it’s inside the tick. When that bacteria moves into a human host, it turns off expression of that protein, which means that you need to kill the bacteria while it’s still in the tick.

So the idea is that the tick takes up the antibodies that get made to the vaccine. And it kills it inside the tick. If it makes it past that level, the protein production shuts off and your antibody has nothing to recognize, and it’s too late.

So it’s really different than the vaccines we have for viruses and COVID, things like that, because those vaccines are all based on allowing you to get infected, ramping up quickly your immune response because it’s now seen it because of the vaccine so that you get infected. But what you get is a much more attenuated disease, whereas with the Lyme vaccine, you’re really preventing getting Lyme disease.

FLORA LICHTMAN: Let me just get this straight. My antibodies would have to go into the tick?

LINDEN HU: Yes, that is correct. So the tick, as it feeds on you, is taking up parts of you. And it’s taking up the antibody with it.

FLORA LICHTMAN: Why this approach for this disease?

LINDEN HU: So I don’t think this necessarily needs to be the approach. This was the most promising target that was first developed. And so this is the one that got carried forward. For animals, for example, there are other vaccines that are based on proteins that are expressed once they get into your body. And so there, you would have a more traditional ability to have what’s called an anamnestic response, where your body ramps up its immune system because it’s seen it before and ramps it up faster and can kill the bacteria, even after it enters the host.

FLORA LICHTMAN: I guess I just– how likely is it that my antibodies are going to go into the tick every single time? Does that always happen?

LINDEN HU: So it happens pretty often. So the vaccine, the original vaccine in the trials, was probably about 80% to 90% effective. So it does happen quite often. I think the thing that’s important to remember, though, is it means that you need to have high antibody levels at the time the tick bites.

So that’s different than a lot of these other vaccines, where your antibody levels dwindle over time. But when you get exposed to it again, they rapidly increase. So here, you can’t have that. And that’s one of the things that made the vaccine difficult in the original vaccine because you needed to get boosters on a regular basis to make sure that you were protected.

FLORA LICHTMAN: Like annually, or more often than that?

LINDEN HU: For the original vaccine, it was annually. I think it remains to be determined for the new vaccines that are coming out.

FLORA LICHTMAN: Why has it taken so long to develop a new Lyme vaccine?

LINDEN HU: I think, honestly, a lot of us didn’t think there would ever be another Lyme vaccine after the first one got pulled. I think there’s the economics of it. These are really expensive trials to do because you need to administer them to a lot of people. And we actually didn’t think another company would invest the money into doing it.

But the demographics of Lyme disease have changed. It’s grown quite a bit. I think that’s probably changed the interest for companies in developing a Lyme vaccine. And now there are multiple companies working on different Lyme vaccines or other preventative measures.

FLORA LICHTMAN: So I was diagnosed with Lyme disease 15 years ago. And I had the signature bullseye rash and symptoms. So the doctor was pretty sure. But I remember the blood tests being a little bit unclear. Am I remembering right? And what’s the state of the diagnostics now?

LINDEN HU: So I think part of it’s right. And a lot of the difficulty with diagnosis is just based on the timing of your own immune response. It takes time for you to form an immune response to the bacteria after you get infected. And so at the time where you still have that– where you have that bullseye rash, you’re usually really early in infection. And it usually takes a couple of weeks to develop a full immune response.

So testing during that early period, right after you’ve been bitten, often is negative. Tests are probably positive around somewhere between 25% and 50% in the first couple of weeks. And then it goes up after that.

A negative test, though, doesn’t mean that you don’t have the disease. So the current recommendations are if you live in a Lyme-endemic area and you have that bullseye rash– and I should mention it’s most commonly not a bullseye rash.

So bullseye rash occurs in a minority of the cases. It’s usually a round, red, oval rash. But if you have that rash, even if your tests– we don’t actually recommend doing the test. We actually recommend just going ahead and treating people at that point.

FLORA LICHTMAN: I want to talk a little bit about chronic Lyme. I’ve heard there’s controversy about whether chronic Lyme even exists. And I know CDC doesn’t call it chronic Lyme, for example. They have a different name for it. Can you parse this for me?

LINDEN HU: That’s a really difficult and touchy question. I think chronic Lyme has been one of the trickiest things to deal with with Lyme disease. Somewhere between 5% and 30% of patients report continued symptoms after their treatment for Lyme disease. It’s really unclear what the cause of those symptoms are. And over the years, I would say there have been lots of different hypotheses and different arguments between different groups about what might be causing it, with not a lot of consensus.

I’ve been working on this for 30 years. And I can say that part of my career is filled with abject failure. So we, unfortunately, don’t have a good diagnostic test for chronic Lyme or what we call Post-Treatment Lyme Disease Syndrome, PTLDS.

So there’s no good diagnostic test, which is the first thing you need to be able to make progress because without it, especially for some of the symptoms that people get long-term with Lyme disease, which are fatigue, brain fog, things that are pretty common in the population in general with or without Lyme– it gets really hard to define a population to study. And I think that’s been one of the big hurdles to trying to make progress on chronic Lyme, or PTLDS. We have currently no consensus treatments, no consensus tests, nothing, unfortunately. And that is a big area that we need to work on.

FLORA LICHTMAN: Is that the big challenge, that you can’t– if you don’t have a diagnostic, you can’t say who has it, and therefore you can’t study what’s causing it?

LINDEN HU: Yeah, that’s one of the big problems, definitely. And so I think if you try to do it just on the basis of symptoms that are pretty common, you end up with people with different causes for those symptoms. So if you end up trying something on those patients, you’re going to get a mixed signal. So I think that is one of the complications.

FLORA LICHTMAN: Does that mean in folks who’ve had Lyme disease, but still have symptoms of Lyme after treatment, that the bacteria are gone? You don’t see any sign of the bacteria anymore?

LINDEN HU: So that’s one of the big areas of controversy. It’s been very difficult to find persistent bacteria after antibiotic treatment. However, there are anecdotal reports of people getting better with antibiotics.

The controlled trials have not shown improvement with antibiotics. But that doesn’t rule out the possibility that there’s a subset of patients that might have improved. So if we’d had that diagnostic and could identify patients, is it possible? Yes. But it’s just one of many hypotheses that are out there about what might be causing symptoms in these patients.

And the CDC is moving towards a characterization calling these infection-associated chronic illnesses. And we see those after a lot of different types of infections. We see similar symptoms. Long COVID would be a classic example of that. And so it’s unknown what’s– what the cause is of all of these, what are called IACIs, Infection-Associated Chronic Illnesses.

FLORA LICHTMAN: What do you think needs to happen scientifically, medically, to make meaningful progress on Lyme?

LINDEN HU: I think a lot of it starts with a well-defined patient population. Can I do a pitch here for what we’re doing?

FLORA LICHTMAN: Sure.

LINDEN HU: So one of the things that’s really hampered studies is that there isn’t a large database or a large biorepository of samples for researchers to use for their studies of well-characterized patient specimens. And so NIH has taken a lot of interest in this recently.

So we have just started a study this month to collect up to 1,000 patient samples from the very first time they get diagnosed with Lyme disease, usually with the erythema migrans rash, which is that classic– I think people think of it as a bullseye, but not often a bullseye, and follow them for a year and a half and see what happens to them in terms of do they get better or do they continue to develop PTLDS, and then use those samples to try and identify things that might define better diagnostic tests or mechanisms that would allow us to test treatments.

FLORA LICHTMAN: Besides vaccines, are there other preventative approaches in the works?

LINDEN HU: Yeah, there are a couple of interesting ones that are in human trials already. So one actually does use antibodies. But instead of giving you a vaccine, it gives you the antibodies preformed. And this was a strategy that was used in COVID. So for people who are vaccine-adverse, this is an option where you can just administer the antibodies. And that will offer protection for three to six months.

The other approach that’s in human trials now is one that’s, again, an– treatment that’s available for your dogs, but not available for humans. And those are anti-tick medications. And so you can give medications that will kill the ticks as they start to feed on you.

Many of the diseases that are transmitted by these ticks require that the ticks be attached and feeding for 24, 48, 72 hours, depending on the disease. And so if you can kill the ticks very quickly, and these drugs do kill the ticks quickly, you can prevent transmission of these diseases. And you can prevent– the nice part about that is you can prevent transmission, potentially, of multiple diseases. So that would be a game-changer if that turned out to be effective.

FLORA LICHTMAN: That’s really fascinating. Well, thank you for joining us. I really appreciate it.

LINDEN HU: Oh, thank you so much for inviting me.

FLORA LICHTMAN: Dr. Linden Hu is an immunologist and Lyme disease specialist at Tufts Medical School in Boston, Massachusetts.

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