In the not-so-distant future, campers and hikers may be able to get a shot that not only protects them from Lyme disease but also from the bloodsucking ticks that spread it—at least if Yale-led research into an anti-tick vaccine continues to show promise. In a new study involving guinea pigs, an experimental mRNA-based vaccine induced an immune response to tick bites that made it harder for the bugs to finish feeding from hosts and to infect them with Lyme bacteria.
Tickborne illnesses are the most common diseases spread by insects or arachnids in the U.S. every year, with Lyme disease being number one. More than 30,000 cases of Lyme are diagnosed annually, though the true toll is likely 10 times higher, according to the Centers for Disease Control and Prevention. Though these infections are largely treatable with antibiotics, undiagnosed cases can lead to serious complications like chronic joint inflammation and nerve damage. Longer summers and warmer winters fueled by climate change have also expanded the range and survivability of disease-carrying ticks, leading to more cases over time.
As with most infectious diseases, a vaccine would be the most practical way to handle the threat of Lyme. There is a vaccine available for dogs, and for a time during the early 2000s, there was one for humans as well. But by 2002, the human vaccine, called LYMERix, was pulled from the market by its makers, who cited “insufficient consumer demand.” The vaccine’s lack of popularity was largely fueled by members of the modern anti-vaccination movement, who spread subsequently debunked claims about its lack of safety.
There are other Lyme vaccines now being developed, with the furthest along by Pfizer having reached Phase II trials this year. But researchers at Yale University School of Medicine and elsewhere are working on a novel type of vaccine that could go beyond just preventing Lyme. Instead of training the immune system to simply recognize Lyme bacteria, their vaccine is meant to make the immune system hone in on its source of transmission: the bite of a female tick.
“All human vaccines directly target pathogens. This would be the first vaccine that does not target the pathogen. Rather by targeting the tick, you prevent the transmission of a pathogen. In this case the Lyme disease agent,” study author Erol Fikrig, an epidemiologist and vector-borne disease specialist at Yale, told Gizmodo in an email. It would also ideally prevent the transmission of other tickborne bacteria and viruses, of which there are many.
The vaccine is supposed to work by immunizing the body to the saliva of a disease-carrying tick. To do this, the vaccine uses a mRNA-based delivery system—the same type used for the Pfizer and Moderna covid-19 vaccines. The mRNA delivers instructions to cells for producing several of the antigens (proteins) found in tick spit that are the most likely to get the immune system’s attention. These antigens will then goad immune cells into a short-lived fight, one that will leave a lasting memory.
Once a tick tries to bite a vaccinated person, the hope is that its saliva will set off an almost immediate immune reaction. This reaction should then make it harder for the tick to naturally finish its meal, which can take up to three days, as well as alert the human to the presence of an ongoing blood theft so that they can safely pull the tick off. Usually, it takes over a day or longer for a bite to pass on Lyme, so interrupting the tick’s dinnertime should also protect against infection. The immune reaction would be most plainly felt as noticeable inflammation and redness at the bite site.
In their latest study, published Wednesday in Science Translational Medicine, Fikrig and his team injected guinea pigs with the experimental vaccine, then introduced them to hungry and sometimes Lyme-carrying ticks. As expected, the skin of these vaccinated pigs reacted to the ticks soon after they munched down. And when compared to control ticks, the ticks on the vaccinated animals could barely feed at all, with many detaching early on their own. Most importantly, when infected ticks were removed from pigs as soon as the reaction was apparent, they avoided Lyme infection.
“We showed that by altering the ability of a tick to take a blood meal, you can prevent an animal from being infected with the Lyme disease agent,” said Fikrig.
Because guinea pigs, like humans, aren’t natural hosts of the ticks that spread Lyme, it’s hoped that the group’s vaccine would create a similar immune response to tick bites in humans (natural hosts tend not to produce much of an immune response to bites in the wild, perhaps a sign of the complex give-and-take dance between a parasite and host). But there’s still more to be done before we can expect an anti-tick vaccine to be available at a doctor’s office.
Some of the saliva proteins the group tested here didn’t generate much of a immune response in this study, for instance, so there may be room for improvement. And even before human trials might start, the team is looking for evidence that the vaccine will reliably work in people. The safety of any experimental drug or vaccine also has to be vetted as much as possible. But the team is moving full steam ahead with their work.
“We are testing the vaccine in other animals,” Fikrig said, “and determining if people with Lyme disease and other evidence of tick exposure have antibodies to some of the targets in the vaccine.”