Lyme disease vaccines are back, one in trials from Pfizer and another in early tests at Penn. But will people get them?

Seamus Naughton Mergner started running a fever one day when he was 3 years old, and he also complained of a stiff neck. His mother, recalling that she had recently removed a tick from his skin, feared that the eight-legged bug had infected the boy with Lyme disease.

The doctor said she was right — and to her relief, Seamus soon recovered after being treated with antibiotics.

But four years later, wary of the tick-laden woods and tall grasses near their central New Jersey home, Taylor Naughton signed up her son for a potential safeguard against another infection. In April, he was injected with the first of four doses in a trial of a vaccine.

That vaccine is being developed by the French biotech firm Valneva and U.S.-based Pfizer, using a traditional protein-based approach that’s been used in other vaccines for decades. If all goes well, physicians predict it could be available to the public within several years.

Another Lyme vaccine is being tested at the University of Pennsylvania, using the school’s messenger RNA technology that worked so well in the Pfizer and Moderna vaccines against COVID-19. So far, Penn’s mRNA Lyme vaccine has been studied only in mice — a long way from proof that it would work in people — but early results are promising.

Yet despite the potential to prevent a widespread disease that can cause severe pain, arthritis, and brain inflammation, a big question about the vaccines remains: Will there be much public demand?

The first time a Lyme vaccine was approved, in 1998, a small number of recipients said it caused arthritis and other adverse effects. Lawsuits were filed. An FDA review found no evidence that the vaccine was at fault, but demand fell off sharply. Manufacturer GSK pulled the product from the market in early 2002, little more than three years after it was approved.

Infectious-disease specialists are optimistic that acceptance of Lyme vaccines will be stronger this time around, despite growing circulation of misinformation about vaccines during the COVID-19 pandemic.

That’s because Lyme disease has become even more widespread in the two decades since the last vaccine was discontinued, as ticks carrying the culprit bacteria are now firmly established across Pennsylvania and much of the eastern United States. The CDC estimates that 476,000 people were diagnosed with Lyme in 2018, up from about 290,000 a decade earlier. A minority of patients have lingering pain and other symptoms for months afterward, a poorly understood phenomenon called post-treatment Lyme disease syndrome.

In a 2018 CDC survey of more than 3,000 U.S. residents, 64% said they were willing to get a Lyme disease vaccine, while 30% were uncertain and 7% were unwilling.

For Naughton, who had Lyme disease herself two years before her son, it was an easy choice. The family raises chickens in a semirural part of Monmouth County, adjacent to a state wildlife management area near Allentown, N.J., and Seamus and his two younger siblings often play outside.

“Our kids are always in the woods or in the tall grass,” she said. “We’re a pretty safe bet for exposure.”

The three children wear long pants and use bug spray when going outside for extended periods. But when Naughton heard about the Valneva-Pfizer vaccine trial earlier this year, she was eager to enroll Seamus, then 6, hoping he could get an extra layer of protection. (The other two children were too young for the trial, which is open to ages 5 to 17.)

Three-quarters of trial participants are randomly selected to get the vaccine. The rest get a placebo, so that researchers can compare the outcomes in the two groups.

Study volunteers are not told which injection they receive, but because Seamus developed a slight fever after his second dose this summer, Naughton is hopeful that he got the real thing. He is scheduled to get his third of four doses in October, at the Pediatric Clinical Research Center at Rutgers Robert Wood Johnson Medical School in New Brunswick.

Sunanda Gaur, a pediatric infectious-disease specialist who is running the Rutgers trial site, predicted that demand for the vaccine will be stronger this time, citing public interest in the trial.

Rutgers planned to enroll more than 50 children. But Pfizer closed enrollment in the trial weeks ahead of schedule, after easily reaching its goal of 3,000 participants nationwide, so Rutgers had to stop with just 13 children, Gaur said.

“Typically, these things are extended, not shortened,” she said.

In September, Pfizer and Valneva reported results from a separate arm of the trial that already was underway with both children and adults. Researchers determined that vaccine recipients had formed a strong immune response, as measured by the antibodies that their immune systems had made against the bacteria that cause Lyme disease. Further study will be needed to see if those who get the vaccine are less likely than placebo recipients to contract the actual disease.

Later that month, Penn and Yale University scientists reported promising results from testing the mRNA-based Lyme vaccine in mice.

Unlike the Pfizer-Valneva vaccine being tested in humans, that mRNA-based Lyme vaccine does not “teach” the immune system by exposing it to proteins from the bacteria that cause the disease.

Instead, the mRNA in the vaccine carries a genetic recipe so that the recipient’s cells can make those proteins inside the body. But it’s the same goal — teaching the immune system by exposing it to a harmless protein fragment from a disease-causing microbe.

The protein in question, called OspA, is located on the surface of the disease-causing bacteria, allowing the microbe to “anchor” itself inside the tick’s gut, said Paul Auwaerter, a Johns Hopkins University infectious-disease specialist. But when a bacteria-carrying tick bites someone who has been vaccinated, antibodies bind to that protein in such a way that blocks transmission.

As with most vaccines, the concept is not foolproof. The vaccine that was discontinued two decades ago contained the same protein, and was about 75% effective, he said. But that is nevertheless a potent level of protection.

The mRNA approach, meanwhile, seems to induce an even stronger response in mice than a traditional protein-based vaccine, said Norbert Pardi, an assistant professor of microbiology at Penn’s Perelman School of Medicine.

Mice that received the mRNA vaccine responded by making both antibodies and T-cells, another key agent of the immune system, he and colleagues reported in the journal Molecular Therapy. And when mice were injected with the bacteria that cause Lyme disease, animals that had received the mRNA-based vaccine were better able to fight off infection than animals injected with a traditional protein-based vaccine.

For COVID, one plus of the mRNA-based vaccines was that they could be quickly updated to match emerging variants. That advantage is less important for the bacteria that cause Lyme, as the circulating strains are more genetically stable, Pardi said.

“The most important advantage is that it works really well,” he said.

Further animal studies are needed before the mRNA Lyme vaccine can be tested in humans. The Pfizer-Valneva vaccine is likely to be approved before then. And Moderna, the other big player in the COVID vaccine realm, also is developing a Lyme vaccine.

It’s a lot of activity in a field that was given up for dead two decades ago. But it can’t come soon enough, said Gaur, the Rutgers pediatrician.

“The more approaches that are in development, the more chances you find something” that works, she said.

Naughton agreed with Gaur that public interest will be higher this time around. She said that once such a vaccine is approved, she planned to get it. In the meantime, when she tells others that Seamus may already have gotten a vaccine, they are envious.

“When we tell family members,” she said, “they’re like, `When can we get our dose?’”