Yale University researchers have developed a novel vaccine that in guinea pigs offers protection against infection by the bacterium that causes Lyme disease and may also combat other tick-borne diseases, they report Nov. 17 in the journal Science Translational Medicine.

Instead of triggering an immune response against a particular pathogen, the new vaccine prompts a quick response in the skin to components of tick saliva, limiting the amount of time that ticks have to feed upon and infect the host, the study shows.

The vaccine is delivered by the same mRNA technology that has proved so effective against COVID-19.

In the United States, at least 40,000 cases of Lyme disease are reported annually, but the actual numbers of infections could be 10 times greater, researchers said. In addition, other tick-borne diseases have also spread in many areas of the U.S.

"There are multiple tick-borne diseases, and this approach potentially offers more broad-based protection than a vaccine that targets a specific pathogen," said senior author Erol Fikrig, the Waldemar Von Zedtwitz Professor of Medicine (infectious Diseases) at Yale and professor of epidemiology (microbial diseases) and of microbial pathogenesis. "It could also be used in conjunction with more traditional, pathogen-based vaccines to increase their efficacy."

The saliva of the black-legged tick Ixodes scapularis, which transmits the Lyme disease pathogen Borrelia burgdorferi, contains many proteins. The investigators focused on 19 separate proteins.

In search for the basis of the vaccine, the Yale researchers, in collaboration with a team led by Drew Weissman at the University of Pennsylvania, analyzed bits of mRNA that produce all 19 of the saliva proteins. A similar strategy was used in vaccines that effectively combat the SARS-Cov-2 virus. And in a series of experiments, they tested the vaccine on guinea pigs, which can be infected with the Lyme disease agent and have also been used as a model to study tick resistance.

Unlike non-immunized guinea pigs, vaccinated animals exposed to infected ticks quickly developed redness at the tick bite site. And as long as ticks were removed when redness appeared, none of the immunized animals developed Lyme disease. In contrast, about half of the control group became infected with B. burgdorferi after ticks were removed. When a single infected tick was attached to immunized guinea pigs and not removed, none of them was infected while 60% of control animals did become infected. If three ticks remained attached to the guinea pigs, however, protection waned even in immunized animals.

In addition, ticks attached to immunized animals were unable to feed aggressively and dislodged more quickly than those on guinea pigs in the control group.

The vaccine enhances the ability to recognize a tick bite, partially turning a tick bite into a mosquito bite. When you feel a mosquito bite, you swat it. With the vaccine, there is redness and likely an itch so you can recognize that you have been bitten and can pull the tick off quickly, before it has the ability to transmit B. burgdorferi."

Erol Fikrig, Senior Author

Researchers did note a caveat in their findings: In similar experiments, mice, which are unable to acquire natural tick resistance after infection, were not protected against Lyme disease after vaccination. In fact, in contrast to guinea pigs, mice are a natural reservoir for I. scapularis ticks, suggesting that ticks may have evolved to develop ways to specifically feed repeatedly on mice. Another possibility may be that guinea pig skin, like human skin, is more layered than the skin of mice.

Fikrig said more study is needed to discover ways that proteins in saliva can prevent infection. Ultimately, human trials would need to be conducted to assess its efficacy in people.

Yale's Andaleeb Sajid, Jaqueline Matias, and Gunjan Arora are co-first authors of the research. Weissman at UPenn is also a co-author. The research was primarily funded by the Cohen Foundation and the National Institutes of Health.