New anti-tick vaccine prevented Lyme disease (in guinea pigs)

A new vaccine prevented guinea pigs from catching Lyme disease from infected ticks in a recent study. Whether it works in humans remains to be seen.

Black-legged ticks (Ixodes scapularis) transmit the bacterium Borrelia burgdorferi, which causes Lyme disease, to about 40,000 people in the U.S. each year, but those are only the cases we know about. The Centers for Disease Control and Prevention (CDC) estimates that the true number of annual cases may be eight- to 10-fold higher than reported, according to a Morbidity and Mortality Weekly Report published in 2018. And with black-legged ticks now expanding into new territory, the pests may soon carry Lyme disease to regions where it wasn't previously a problem, Live Science previously reported.

Now, scientists have developed a tool to prevent the spread of Lyme disease: A vaccine that stops ticks from feeding properly once they latch onto a host's skin, which stops the pests from transmitting B. burgdorferi. In guinea pigs, the new vaccine provided "robust tick immunity," but more research is needed to see if it provides similar protection to humans, the research team reported Wednesday (Nov. 17) in the journal Science Translational Medicine. 

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"This is the proof-of-concept that this is possible," said Petr Kopáček, a senior scientist at the Institute of Parasitology at the Czech Academy of Sciences in South Bohemia, who was not involved in the study.

Triggering anti-tick immunity

Some animals, including guinea pigs and rabbits, develop a natural resistance to tick bites after being repeatedly bitten by the parasitic pests, said senior author Dr. Erol Fikrig, a professor of medicine who runs an infectious disease lab at the Yale School of Medicine. These resistant animals develop an inflamed, red welt at the tick bite site, and this immune reaction interferes with the tick's ability to slurp down the animal's blood. Often, the tick will fall off the animal without completing its meal — and before pathogens can be transferred. 

And anecdotal evidence suggests that humans can build up such resistance to ticks, as well, Fikrig told Live Science. So Fikrig and his team wondered if humans could be granted tick immunity, through a vaccine, and thus become better protected from tick-borne pathogens like B. burgdorferi. 

"When a tick feeds, it takes a bit of time for the Lyme vector to be transmitted," Fikrig said. Typically, a tick must remain attached to its host for 36 to 48 hours for the bacteria to transfer over, according to the CDC. The tick's spit actually helps it to avoid discovery during its feeding, because the pest's saliva contains proteins that suppress the host's immune response, which reduces the amount of pain and inflammation triggered by the bite.

Fikrig and his team decided to use these ticks' spit proteins against them, by designing a vaccine that mounts an immune response specifically against those proteins. 

In total, they chose 19 tick spit proteins to target, some of which suppress the host immune response and others that help the tick feed — for example by dilating the host's blood vessels and preventing the blood from clotting. The team then generated mRNA, a type of genetic molecule, that contained instructions on how to build each spit protein, and packed that mRNA in lipid nanoparticles, or tiny bubbles of fat. Once injected into guinea pigs, the mRNA directed the guinea pig cells to build the tick saliva proteins and trigger a subsequent immune response.

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The COVID-19 vaccines designed by Pfizer-BioNTech and Moderna also use mRNA, but those vaccines instruct human cells to build coronavirus proteins. "Reviewing this manuscript, I was quite excited, because it's the first effort to get an mRNA vaccine against ticks," Kopáček said.

Two weeks after vaccinating the guinea pigs, the team examined their blood and found specific antibodies against 10 of the 19 tick proteins included in the vaccine. The researchers then placed uninfected black-legged ticks on the animals to see if their bites would trigger an immune response. The vaccinated guinea pigs developed "substantial" redness around the tick bites within 18 hours, and this redness peaked at 24 hours. By comparison, a group of unvaccinated guinea pigs showed little redness around their bites.

The ticks attached to the vaccinated guinea pigs consumed little blood and began to detach within 48 hours; 80% had completely detached after 96 hours, while only 20% of ticks on the unvaccinated guinea pigs fell off within the same time period.

To see whether the vaccine could help reduce the risk of Lyme disease from a tick bite, the team conducted a second experiment, in which they placed three B. burgdorferi-postive ticks on each guinea pig. (It only takes one infected tick to cause Lyme disease.)

Given that humans would likely notice and remove a tick if it caused substantial redness on their skin, the team removed the ticks from the guinea pigs once redness developed around their bites. Following the experiment, six of the 13 unvaccinated guinea pigs tested positive for B. burgdorferi, but none of the vaccinated guinea pigs did.

"The authors demonstrated that early tick removal, together with the [vaccine]-driven inflammatory reaction around the tick bite, is a key step toward the development of a vaccine for preventing Lyme disease transmission," Kopáček and several colleagues wrote in an accompanying commentary, also published in Science Translational Medicine.

Theoretically, the new vaccine may not only guard against Lyme disease but also prevent the transmission of other tick-borne pathogens, such as Babesia microti — a parasite that causes the illness babesiosis, which destroys red blood cells, according to the CDC. But this would need to be demonstrated in future studies, Fikrig said. He and his colleagues hope to pursue such studies in animal models, and in the meantime they are studying each of the tick saliva proteins in the vaccine, to see which are most important for generating immunity from ticks. 

This research is in its early stages, so a human version of the anti-tick vaccine likely won't be available anytime soon. The authors suspect that humans may respond to the vaccine "in a manner similar to guinea pigs," because neither people nor guinea pigs are important to the natural life cycle of I. scapularis and both show (at least anecdotal) resistance to tick bites over time. Mice, on the other hand, act as one of the primary food sources for young ticks, and don't build up resistance to their bites; as part of the new study, the authors tested their vaccine on mice and found they did not develop any skin redness after tick exposure. 

For humans, "I think showing safety would be the most important thing," on top of showing that the vaccine works, Fikrig said. For instance, it's unclear whether the vaccine could trigger hypersensitivity to other biting arthropods. "If there's hypersensitivity, I'd expect it to be another tick species," rather than another blood sucker, such as mosquitoes, but this still needs to be tested, Fikrig said.

A future vaccine for humans could potentially combine the new, tick-targeting vaccine with one that targets the B. burgdorferi bacteria directly, Kopáček said. "I can imagine that this mRNA technology can easily combine both approaches," which together would provide even more protection against Lyme disease, he said. 

Several vaccines that target B. burgdorferi are now in clinical trials, and one such vaccine was actually approved in the 1990s, but it was discontinued in 2002 due to "insufficient consumer demand," according to the CDC. But the threat of Lyme disease seems to be better recognized now, and federal institutions are once again investing in Lyme disease vaccine development, Time reported.

Originally published on Live Science.