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Vaccinating Mice May Finally Slow Lyme Disease

Kirby Stafford, Connecticut’s state entomologist, knows only one surefire way to reduce tick populations enough to cut Lyme disease rates: killing deer. Otherwise, he says, “very little by itself really reduces tick numbers enough.”

But in some Connecticut neighborhoods Stafford has been testing a new strategy, one he hopes might show real promise after years of stymied efforts to drive new Lyme infections down: a vaccine for mice.

Roughly half of ticks carrying Borrelia burgdorferi, the bacteria that cause Lyme disease, pick it up by biting infected white-footed mice. That makes these fist-size fuzz balls the most important carriers of the bacteria and a prime target for a Lyme vaccine, Stafford says. In theory, vaccinating enough mice should lower the number of ticks that acquire Borrelia in the first place. And fewer infected ticks means fewer infected bites on humans.

The U.S. Centers for Disease Control and Prevention learns of roughly 30,000 cases of Lyme disease each year, but not every diagnosis gets reported to the CDC, and the actual number of new infections is likely over 40,000. That makes Lyme the most common disease transmitted by ticks, mosquitoes or fleas in the U.S. If untreated, it can go from rashes, swelling and joint pain to brain damage, weakened muscles and numbness that, in rare cases, can sometimes linger or recur for years.

Researchers began looking into wildlife vaccines for the disease shortly after problems developed with a human Lyme vaccine, says Maria Gomes-Solecki, an immunologist at the University of Tennessee and the creator of the mouse vaccine Stafford is testing in Connecticut. The human version, brand-named LYMErix, came onto the market in 1998 and was effective in adults after three doses. But it quickly became controversial as lawsuits emerged alleging it caused severe joint inflammation, along with other Lyme symptoms it was supposed to prevent.

Gomes-Solecki claims those allegations were never supported by statistical evidence but were “blown out of proportion” and stoked by anti-vaccine sentiment. “There are many reasons why vaccines are pulled from the market,” she says. “I don’t think these reasons were scientifically justified [in this case].” Still, the concerns halted sales enough that SmithKline Beecham (now GlaxoSmithKline) pulled the vaccine off the market four years after its introduction.

Gomes-Solecki and other immunologists began searching for new Lyme vaccines for humans, but she says nothing worked as well as the original. LYMErix is based on a protein called outer surface protein A (OspA), found on the surface of Borrelia bacteria. The vaccine trains the immune system to recognize that protein and manufacture defenses against anything carrying it. And when a tick slurps up blood from a vaccinated individual, those defenses also destroy any Borrelia inside the tick—preventing it from infecting a new host.

Gomes-Solecki—who was a veterinarian before becoming an immunologist—says she found the science around Lyme disease fascinating, and emigrated from Portugal to the U.S. to study it. “With my background being veterinary medicine, I started thinking, ‘If we can’t use [the vaccine] in humans, maybe we can target the animals that cause the illness,’” she says.

That hunch got its first real test in 2004 when a team of Yale University scientists (of which Gomes-Solecki was not a part) tested an OspA vaccine, designed for mice, on the rodents. It proved effective against Borrelia infection and in clearing the bacteria from ticks that bit an immunized mouse—but it was impractical. “Part of the problem with previous methods is they would capture wildlife and do injections,” says Joyce Sakamoto, a tick biologist at The Pennsylvania State University who is not involved with Gomes-Solecki’s research. “It’s incredibly laborious. Animals sometimes die in traps; that doesn’t help. Injections are very difficult.” In short, no one could ever vaccinate enough mice to make a dent in the Lyme epidemic using needles, Sakamoto says.

So Gomes-Solecki came up with something that could be broadcast into the environment like seeds: kibble that contains an oral vaccine but would be tasty to white-footed mice. “It’s our secret sauce, if you will,” says Mason Kauffman, a spokesperson with US BIOLOGIC, the company that Gomes-Solecki helped found to manufacture the mouse Lyme vaccine. The company designed the vaccine with layers “like a peanut M&M,” Kauffman says. In this case the “peanut” is a gray pet food pellet animal food–maker Purina Mills custom manufactured for the vaccine. “The ‘chocolate coating’ around the peanut is the vaccine, then the ‘candy coating’…is a coating that protects the vaccine from stomach acids,” Kauffman says. The vaccine enters the bloodstream through the animal’s intestines.

The vaccine should erode Lyme disease’s pervasiveness steadily each year it is deployed, Gomes-Solecki says. Black-legged ticks only eat twice in their lives. Their first blood meal comes when they are larvae and feed exclusively on small animals like mice, shrews or birds. They pick up Borrelia if they bite an infected host, so the key is to immunize mice before black-legged larvae bite them. The next year, when the larvae have grown into nymphs and are looking for a second meal—either from small animals or larger ones such as humans or deer—fewer of them should carry Lyme.

Gomes-Solecki tested the kibble vaccine from 2007 to 2011 using seven fields, each roughly the size of a football field. In each one she set box traps so she could capture and study the local mice. She put the vaccine inside the traps in four of those fields. After five years the prevalence of infected ticks in some of the fields had dropped by 76 percent, but had risen by 94 percent in the fields without the vaccine. “[The results] were massive. If we could see that in deployment, it would be incredible,” she says. “I thought, ‘Yes, maybe—maybe this could work.’” It was a moment that paid off in a literal sense, she adds. The study had overextended its funding, leaving insufficient funds for the last year of experiments. “To finish the last plot, I [had] put in $20,000 of my own money,” she says.

The results, published in 2014, are “encouraging but also a bit puzzling,” says Marm Kilpatrick, a disease ecologist at the University of California, Santa Cruz, who has not worked on the vaccine. “You should see this steady decline from year to year,” he says. “The slight challenge of that is the data don’t completely support that going on.” Data from two fields where Gomes-Solecki’s team used the vaccine show a gradual fall in infected ticks, Kilpatrick notes, but data from a different vaccinated field showed no effect from the vaccine until the third year of the experiment. “It falls to 13 or 14 percent [from 55 percent], which is awesome and fantastic,” he adds. But those fluctuations give him pause because unvaccinated fields in Gomes-Solecki’s experiment also showed significant variations from year to year. Therefore, “you better be very careful when interpreting fluctuations on your treated plots,” Kilpatrick says.

On the other hand, Gomes-Solecki says when averaging all fields that had the vaccine together, a sustainable decline in Lyme prevalence was evident. The fields without the vaccine only saw more Lyme appear during the study period.

In any case, Kilpatrick is optimistic about the vaccine’s future for two reasons: First, if the kibble is placed in open containers rather than traps, more mice might be willing to eat it. A true deployment of the vaccine would also cover more ground, he says, whereas this study might have been tainted by rogue mice traveling in and out of Gomes-Solecki’s small plots. “I think this study design represents the lower estimate of [the vaccine’s] efficacy,” Kilpatrick adds.

That idea seems to be on the right track, according to study results from Stafford—the Connecticut entomologist—who has been testing the vaccine on a larger scale. When Stafford deployed the kibble across the lawns of 22 homes in Redding, Conn., he says the researchers were able to show over 90 percent of mice were eating it. The final results from that study, to be published later this year, are promising but not magical, he notes. “I think [the vaccine] will be a valuable tool in the tick management box,” he says. Using it in areas where Lyme prevalence is extreme—including his home area in suburban Connecticut—could yield a lot of bang for the buck, he says.

There are likely two things standing in the way of the kibble vaccine becoming an ultimate solution for Lyme disease, Kilpatrick says. The first is scientific: The vaccine targets white-footed mice—but shrews, chipmunks and birds also carry Lyme bacteria and can transfer them to ticks as well.

The second reason, Kilpatrick says, is social: “For reasons that are not clear, mosquito control is usually done by county or state health departments, where tick control is not,” he notes. “The result of that is it’s beholden upon you and I, as the lay public, to do our own control of ticks.” He adds there are known ways to manage the arachnids, including the use of fipronil bait (a tick-killing agent commonly known by the brand name Frontline). “The reason why we don’t do it is because people are scared or lazy or both—and then it just doesn’t get done.” Even if the mouse vaccine works spectacularly, Kilpatrick says, it will hardly make a difference unless there is a concerted effort to deploy it.

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