T he term “mRNA vaccine” has entered the public lexicon since the rollout of COVID vaccines late in 2020. But the technology has other applications as well, including a potential Lyme disease vaccine that’s under development in a lab at the Yale School of Medicine.
For those who need a primer, traditional vaccines work by injecting a small dose of microbes or microbial proteins directly into the body, which then attacks that foreign agent and builds up antibodies in response. If it comes in contact with that antigen again, the immune system will be trained to handle it. In contrast, mRNA vaccines don’t inject microbes or proteins directly. Instead, they inject mRNA—messenger ribonucleic acid—coded to teach the body how to make a targeted protein itself and then respond to it.
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The mRNA in the Lyme vaccine being tested in the lab of Dr. Erol Fikrig at Yale encodes for 19 of the proteins found in the saliva of Ixodes scapularis, commonly known as the deer tick. When vaccinated guinea pigs in the lab were bitten by ticks, the vaccine prompted an immune response that was visible as skin redness, or erythema, at the site of the bite. This immune response prevented ticks from feeding properly and thereby reduced transmission of Borrelia burgdorferi, the bacteria that causes Lyme disease. The research team hypothesized that redness and itching at the site of a tick bite could serve an additional function: helping future human subjects/hosts recognize that they’ve been bitten and remove ticks quickly, which could also help reduce transmission, says Gunjan Arora, an associate research scientist in Fikrig’s lab and one of 14 authors of the paper “mRNA vaccination induces tick resistance and prevents transmission of the Lyme disease agent,” published in November in the journal Science Translational Medicine.
Researchers have been working on immunity to tick-borne diseases since the late 1930s, Arora says, and many more questions remain. For example, there are more than 100 proteins in the saliva of Ixodes scapularis, and the functions of some of them remain unknown. Are these 19 the right proteins to code for in a vaccine? How long does it take for the bacteria to transfer to the host? And—the next question for Arora and his colleagues—how will the vaccine work in other animal models? There are myriad ways in which researchers might choose to “improvise” on the vaccine. And before it could come to market for use in humans, the number of immunizations and their dosage would have to be worked out, too.
Nevertheless, Arora says Yale’s vaccine or a similar candidate could be “game-changing” because it isn’t targeted at a specific pathogen, such as Borrelia burgdorferi. Instead, it provokes an immune response to proteins in tick saliva itself and inhibits the transfer of other pathogens slowly transmitted by ticks, such as parasites and other bacteria. In essence, the vaccine would provide “a big umbrella,” Arora says, rather than “a small protection from one pathogen itself…”
Although the Yale vaccine uses the same mRNA technology as the COVID vaccine, it wasn’t inspired by it, Arora says. However, COVID vaccines are giving Lyme vaccine research a boost. When the Lyme studies began, mRNA vaccines had not yet been tested on a large-scale population. Thanks to COVID, that hurdle has now been jumped. One advantage of using mRNA in the case of the Lyme vaccine is that “you don’t have to make 19 antigens individually,” Arora says. And the mRNA itself is created through “a simple biochemical reaction,” which makes these vaccines easier and quicker to produce.
Research studies like this one are happening all the time, unseen and unsung, behind the School of Medicine’s walls. Arora himself co-authored another paper, published in December in the journal Vaccine, which studied a specific antigen in the tick saliva and helped to identify its role. But on a day-to-day basis, he says, researchers aren’t necessarily dreaming of their next big breakthrough.
“You have to know that things—they work very fast one day, and there will be times or years or months [when] you have to be really patient,” Arora says. Even when research isn’t groundbreaking, scientists are learning things that may be applicable to their contemporaneous or future work. (Arora, for example, also studies the immunopathogenesis of malaria.) No one person will solve a big problem like how to protect humans from Lyme disease or COVID, he says. “Everybody has a different background, so we come together, and then we use our skills which we have learned before.”
Written by Kathy Leonard Czepiel. Image by PhotoPixel Studio/Shutterstock.
