How mRNA technology could create a new vaccine — against ticks

Climate change, a negative force for so many types of native flora and fauna in the U.S., has been an enormously positive development for ticks. As temperatures rise across the nation, more of the U.S. has become hospitable to ticks, and the prevalence of diseases carried by ticks has increased. Approximately 500,000 Americans are now diagnosed with Lyme disease, the most common tick-borne disease, annually — double the number of cases reported in the 1990s. Rocky Mountain spotted fever, a previously rare bacterial disease that can cause fever, rash, headache and, in very severe cases, death in humans, is on the rise. So is babesiosis, a parasite that infects red blood cells and causes malaria-like symptoms.

Right now, there is no coordinated national response, as there is for sexually transmitted diseases or COVID-19, to tick-borne disease in the U.S. State health departments are required to report cases of Lyme and some other tick-borne illnesses to the Centers for Disease Control and Prevention, but the burden of protecting oneself from ticks and seeking out a diagnosis and treatment for a tick-borne illness is still shouldered almost entirely by individuals. 

A vaccine against tick-borne illnesses would help alleviate some of that burden. But prior attempts to distribute such a vaccine have failed spectacularly. A moderately effective vaccine for Lyme disease, called LYMErix, was used in the late 1990s and early 2000s, but its manufacturers withdrew it after just a few years on the market after a lawsuit from a group that claimed the vaccine caused arthritis problems, despite negligible evidence that it did anything of the sort. The saga had a chilling effect on tick vaccine research for decades. 

Now, a group of researchers at Yale University is trying to revive a Lyme vaccine — and their new effort looks nothing like the LYMErix of years past. In fact, if it ends up working in humans, it won’t just protect against Lyme disease; it would protect against ticks more generally. 

By using messenger RNA — the same technology that Pfizer and Moderna used in their COVID-19 vaccines — the researchers were able to pack 19 different kinds of proteins found in tick saliva into a single vaccine. Then, they administered those vaccines to guinea pigs and attached Lyme-carrying black-legged ticks to the animals. Once ticks attach to a host, they don’t let go until they’ve filled up on blood, which can take days. The researchers found that the vaccine, currently called 19ISP, may be effective in preventing not just Lyme disease in guinea pigs but other types of other tick-borne illnesses, too. 

The vaccine works in two ways. First, it makes tick bites inflamed, itchy, and red. Tick bites usually don’t itch, which makes it hard for humans to notice them and pull ticks off. The longer a tick gets to feed undetected, the higher the chances that it will impart whatever disease it’s carrying into the bloodstream of its host. Not all ticks carry disease, but if they are harboring Lyme bacteria or some other pathogen, transmission of that disease can be stopped in its tracks if the tick is removed early. 

The vaccine also works by decreasing the amount of time that a tick wants to feed on its animal host. Ticks that attached to guinea pigs that had received 19ISP fed poorly, the study showed, and started to detach from the animal by themselves 48 hours after they started sucking blood. By the 96th hour, 80 percent of the ticks that had been attached to guinea pigs that had received the vaccine were detached. By comparison, only 20 percent of the ticks that had attached to guinea pigs in the control group had detached by themselves within 96 hours. The researchers found that when Lyme-infected ticks were removed from the guinea pigs when the tick bite became itchy and inflamed, mimicking what a human would do once they noticed an inflamed tick bite, none of the animals later tested positive for the disease. Almost half of the control group of guinea pigs tested positive for Lyme.

“This tick usually feeds for three to five days,” Erol Fikrig, a professor of epidemiology at Yale University and one of the study’s authors, told Grist. “This vaccine makes it so that those ticks feed for half that time. It’s like if I gave you a rotten apple, you wouldn’t eat it all. So these ticks don’t feed properly.” 

The combination of better detectability and less efficient feeding has the potential to make this vaccine effective not just in preventing Lyme disease, but other tick-borne illnesses, too. “Other tick-borne diseases are transmitted more slowly or more rapidly,” Fikrig said. “We’re likely to get some degree of protection if the target is something that is transmitted slowly from a tick. But protection is likely to be less if the infectious agent is transmitted rapidly from a tick.” 

Fikrig and his coauthors don’t have data yet that would show whether their vaccine could be effective against other types of tick-borne illnesses, though they feel comfortable hypothesizing that it could be. They also haven’t tested it on ticks other than black-legged ticks yet, so future experiments need to be done on the American dog tick as well as other ticks found in the United States. The next phase of their research will focus on identifying which of the 19 agents in 19ISP produced the immune response in the guinea pigs and turning that strain or multiple strains into its own vaccine. 

It’s worth noting that this vaccine hasn’t been tested in humans yet. The idea for the vaccine was sparked by evidence that some animals develop natural immunity to ticks. In other words, some ticks feed poorly on animals that have been bitten several times. There’s anecdotal evidence that the same may be true for humans who have been bitten a lot, Fikrig said. But not all animals develop this natural immunity. Guinea pigs, for example, can develop it. Mice, however, don’t. 

“One big question to ask when it comes to taking next steps is whether the human immune system behaves more like guinea pigs or more like mice,” Richard Ostfeld, a disease ecologist at the Cary Institute of Ecosystem Studies in New York who was not involved in the vaccine research, told Grist. “If we’re more like mice, then this might not work for us. If we’re more like guinea pigs, it might. And I don’t think we know the answer to that question yet.” 

Despite the caveats, Ostfeld is heartened by the research thus far. “This could be central to a national response that would actually begin to take the responsibility off of individual patients. Right now, we’re responsible for buying our own DEET, buying our own protective clothing, and doing our own tick checks,” he said. “Prevention is really where it’s at. We should be leaving no stone unturned and I think some kind of centralization of our response has to happen to take away that individual burden that is so problematic.”


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