We Used to Have a Lyme Disease Vaccine. Are We Ready to Bring One Back?

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Photo: Sol Cotti for TIME

At my animal hospital in upstate New York, an epicenter of the U.S. tick epidemic, my dog Fawn lets out a whimper as the veterinarian injects her with her annual Lyme disease shot. I roll my eyes. She doesn’t know how good she has it.

The injection means that if a tick bites her (and in rural New York, a tick always does), the creepy crawly will feast on dog blood that’s been supercharged with a Lyme bacteria-killing substance, and Lyme disease won’t be transmitted to Fawn.

I wish I could be shot up with that superpower. Currently, there is no human vaccine for Lyme disease—even though more than two decades ago, people could get a safe and effective preventative shot similar to Fawn’s. Now, thanks to potent anti-vaccine pushback, all we can do is try to avoid getting bitten by the tiny, vampiric nightmares. A tick can’t fly or jump; instead, it “quests,” or waits on a blade of grass or on the leaf of a bush for you, your dog, or any other furry host to brush by. It then crawls up your body, finds a good place to feed, cuts your skin open with tiny incisors, and sticks in a feeding tube, through which it slowly takes a blood meal. You don’t feel any of this, thanks to a numbing substance in tick saliva that lets it feed in secret (so good luck trying to swat a tick away).

And that’s the benign part. Once a tick starts sucking your blood, its saliva—which can carry all sorts of pathogens—enters your bloodstream. That’s how people contract Lyme disease, by far the most common vector-borne illness in the U.S., according to the U.S. Centers for Disease Control and Prevention. A bullseye-shaped rash shows up at the bite site in about 70-80% of people who ultimately are determined to have Lyme. In those cases, it’s relatively straightforward to diagnose and treat with several weeks of antibiotics, which work best when given early on in the infection. But if you don’t get that rash, you might not even know you’ve been bitten, and fever, headache, fatigue, chills, and joint pain can come on with no warning. Later signs of Lyme can include nerve pain, neck stiffness, sudden weakness in facial muscles, arthritis, heart palpitations, cognitive problems, and brain and spinal cord inflammation. Some cases become chronic—what the CDC calls “post-treatment Lyme disease syndrome”—with mysterious symptoms lasting more than six months after treatment.

Lyme disease is rarely fatal, but it can make life extremely unpleasant. Not every case responds well enough to antibiotics, and prolonged illness is more common and serious than once thought, shows research from the Johns Hopkins Bloomberg School of Public Health published in 2015 in the journal PLOS One. Lyme disease costs the U.S. health care system between $712 million and $1.3 billion every year—an average of about $3,000 per patient—in testing costs and repeat doctor visits. In the analysis, people with Lyme disease had 87% more doctors’ visits and 71% more visits to the emergency room in the year after their diagnosis compared to demographically similar people who didn’t have Lyme.

Lyme disease, discovered in Lyme, Conn., in 1975, is caused by a tick-transmitted bacterium called Borrelia burgdorferi. Though it is often associated with the northeastern United States, the illness is found in many parts of North America and in Asia and Europe, and several different strains of the B. burgdorferi bacteria can cause it depending on the region. Tick-borne diseases are on the rise across the U.S. and around the world, with reported cases in the U.S. reaching record highs in recent years. The number of reported Lyme disease cases in the U.S. has at least tripled since the late 1990s, the latest CDC data suggest. Each year, about 476,000 Americans are diagnosed and treated for Lyme disease.

A warming climate is one reason for the explosion in human exposure to ticks; another is increased land development on previously forested areas, putting people in closer contact with deer, mice, chipmunks and other tick hosts. U.S. cases of Lyme outnumber any other mosquito- or tick-borne disease by many thousands per year, but scientists have identified at least a dozen other such illnesses in the U.S., plus more abroad. Some are caused by bacteria transmitted by ticks, others by viruses. And some have truly weird effects in humans, like alpha-gal syndrome, in which a bite from an infected tick can trigger a red-meat allergy. Others, like the recently discovered Powassan virus, can be deadly and have no known treatment.

The best way to protect against the growing threat of tick-borne diseases is through vaccines, as Dr. Anthony Fauci and his colleagues at the National Institute of Allergy and Infectious Diseases argued in a 2018 paper published in the New England Journal of Medicine. No human vaccines for Lyme exist. But that wasn’t always the case. Before Lyme disease shots went to the dogs, people had a safe and effective vaccine, approved by the U.S. Food and Drug Administration (FDA) in 1998. But anti-vaccine forces claimed it was dangerous, tanked its popularity and sued it out of existence after just a few years on the market.

However, there are now several new options in the pipeline, and scientists are crossing their fingers that these don’t meet the same fate.

The only Lyme disease vaccine ever approved by the FDA was developed in the 1990s. Called LYMErix and manufactured by GlaxoSmithKline (then SmithKline Beecham, or SKB), it worked in a unique way. Unlike most vaccines, which stimulate a person’s immune system to make antibodies that fight off a germ once it enters the person, LYMErix instead “immunized” the tick against its own dangerous bacteria. If a tick were to take a sip of a vaccinated person’s blood—now full of bacteria-neutralizing antibodies—the pathogens in the tick’s gut would be killed before they could be transferred to the human. “It had a very sexy, interesting mechanism of action,” says Dr. Robert Aronowitz, a physician and medical historian who wrote a detailed account of the history of Lyme disease vaccines for a 2012 issue of the health journal The Milbank Quarterly. LYMErix, which was given in a series of three shots, proved to be safe and about 75% effective in reducing the risk for infection in clinical trials.

The FDA approved LYMErix in 1998, but with a great deal of ambivalenceEven after the vaccine’s approval, members of a CDC advisory committee disparagingly called it a “yuppie vaccine” for affluent suburbanites who “will pay a lot of money for their Nikes and their Esprit and shop at L.L. Bean’s (sic) [and] will have no consideration for cost-effectiveness when they want a vaccine because they’re going to travel to Cape Cod.” In other words, Lyme was seen as a champagne problem: a mild, treatable disease that affected a small number of people only in certain—wealthy—regions.

Federal regulators and advisory boards were also concerned about LYMErix for other reasons, Aronowitz points out. Booster shots to the three-dose regimen were thought to be needed at some point. The trials hadn’t yet included children. Most of all, regulators were worried that LYMErix might cause some unknown side effects down the line. The fear was that the vaccine might, hypothetically, trigger an autoimmune reaction in some people that would cause the very same long-lingering symptoms of Lyme disease cases that don’t always respond to antibiotics, like arthritis and chronic fatigue.

Scientists took the speculation seriously, but it was later disproven in long-term follow-up studies. Still, the very notion had been enough to turn the public against the vaccine. Lyme advocacy groups “latched onto the vaccine as being a horrendous thing, a cause of chronic fatigue and other persistent Lyme [symptoms],” says Dr. Neal Halsey, founder and former director of the Institute for Vaccine Safety at the Johns Hopkins Bloomberg School of Public Health, who chaired SKB’s data and safety monitoring committee for the LYMErix Phase 3 trial. “They quickly became anti-vaccine, even though you would think they would be pro-vaccine.”

In 1999, more than 100 people who had taken LYMErix filed a class-action lawsuit against SKB for the perceived negative side effects they experienced. The CDC and FDA continued to monitor adverse events in the years following the vaccine’s approval but found no higher incidence of arthritis or any other serious side effect in vaccinated people. Neither did post-licensure safety trials conducted by SKB. Yet the negative attention pummeled vaccine sales. LYMErix sales dropped from about 1.5 million doses in 1999 to about 10,000 in 2002, and that year, SKB (by then GlaxoSmithKline) voluntarily pulled it from the market. A year later, the company settled the class-action lawsuit, while continuing to deny that the vaccine had caused harm.

Lyme vaccine scientists felt burned after more than a decade of work. “I was surprised and annoyed and even a bit angry,” Halsey says. “I really thought settling the class-action lawsuit and taking it off the market was a mistake. I still believe that.” Most scientists moved on to different pursuits, and some find it hard to discuss those painful years even now. “Lyme disease is the only infectious disease that I know of for which we have a vaccine that’s been shown in Phase 3 trials to be safe and effective, but that is not available to the public,” says Dr. Allen Steere, professor of medicine at Harvard Medical School and director of translational research in rheumatology at Massachusetts General Hospital. Steere is credited with discovering Lyme disease and was the principal investigator of the Phase 3 LYMErix vaccine trial. “When is the scale finally going to tip? When are there going to be enough cases and enough people affected that [Lyme vaccination] really becomes a potent, societal force?”

That time may be now. In 2020 and 2021, the U.S. National Institutes of Health funded more than $6 million in tick disease-prevention projects—many of them for vaccine development. Several new vaccines for Lyme disease are on the horizon, and in exciting but early work, researchers are even trying to develop vaccines that target ticks themselves, potentially protecting against a wide range of illnesses the tiny arachnids carry.

The furthest along is a vaccine candidate co-developed by Pfizer, the U.S.-based pharmaceutical giant, and Valneva SE, a French biotech company. In March, the companies kicked off a Phase 2 trial in 600 people ages 5-65. The vaccine, which would be given in two to three doses, is very similar to LYMErix, but it targets six strains of Lyme bacteria—not just those common in North America, but in Europe as well—instead of the single strain that LYMErix targeted. Finding volunteers to take it has been easy, aside from a lull during COVID-19 lockdowns, says Thomas Lingelbach, president and CEO of Valneva. “The tick issue has reached a completely different scale,” he says. “Ticks are everywhere. Fortunately, there is a high and increasing level of awareness.”

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