Yale researcher: Lyme vaccine is first of its kind
Yale University researcher Erol Fikrig says the Lyme disease vaccine he’s developing is the first of its kind in two ways.
Unlike any previous attempt to vaccinate against Lyme, it’s based on mRNA technology, the same used to build the Pfizer and Moderna vaccines developed to fight COVID.
But to Fikrig, that is not the most interesting part. The real breakthrough, Fikrig says, is that his vaccine is the first that does not target the disease itself.
“Every vaccine that you and I have had, every vaccine that has ever been made, is directed against the pathogen, against a microbe,” he said. “This is the first example of a vaccine against an infectious disease that does not target a microbe.”
Instead, the vaccine being developed by Fikrig and his team targets the disease carrier — in this case, the deer ticks that transmit the disease.
More specifically, the vaccine targets the tick’s saliva, and exploits the time it takes for the Lyme bacteria to go from the tick into your bloodstream.
Unlike with mosquitoborne illnesses like malaria, transmission of Lyme is not fast. In fact, it takes about two days.
“When it bites you, it feeds for about four to five days. And it really starts engorging, taking the blood meal, at about 24 to 48 hours,” Fikrig said.
All the while, the bacteria that causes Lyme, a spirochete called Borrelia burgdorferi, “lives inside the tick gut, and it stays there sort of sleeping, resting,” Fikrig said.
“In response to the blood meal, it gets activated, then it moves out,” he said. “It doesn't move out of the tick until about day one or day two. So there's a window of one to two days where the tick is attaching to you, feeding, but the spirochete has not yet been transmitted.”
When a mosquito bites, it injects a proboscis, and you feel it immediately, Fikrig explained. The response is usually to slap the bug in the hopes of dislodging it. Ticks do the same, inserting something called a “hypostome,” but you don’t feel it.
“Most likely, it's because when ticks bite you, they inject salivary components that have the ability to numb you locally,” he said. “That's part of it. That's one of the hypotheses, and it's a likely one.”
Fikrig’s vaccine does two things: It takes the silencer off the tick bite, making it red and itchy before the bacteria has the chance to move from the tick to a new host, and makes the ticks feed poorly and fall off the body far sooner.
“I don't think that’s as important as identifying redness, and recognizing the tick bite, because I've never heard of anybody who's noticed the tick on them and hasn't pulled it off within three, four minutes,” he said.
Fikrig had been investigating what he called “tick resistance” for more than a decade with limited success. It wasn’t until mRNA technology became available that his breakthrough happened.
“We've been using mRNA since 2019, about eight months before the pandemic occurred,” he said.
The idea of tick resistance is an old one. Sixty years ago, a researcher named Bill Trager noticed that animals develop resistance to tick bites. Trager’s research, like Fikrig’s, involved intentionally putting ticks on guinea pigs.
“He let them feed, and they all fed happily. He came back a month later, put another bunch of 30 ticks on those same guinea pigs, they fed poorly,” Fikrig said of Trager. “And he came back another month later, none of them fed at all. So animals naturally acquire tick resistance.”
The question then became how does resistance occur, biologically, and how to exploit it.
“The hypothesis we had is that when a tick bites you, it secretes saliva to the bite site, and your body develops an immune response to that saliva,” Fikrig said. “So, if we could reproduce that by taking salivary protein targets and putting them in an mRNA vaccine, that might elicit the same phenomenon.”
Fikrig is leaving commercial development of his vaccine, including human trials, to private interests. He’s now hoping to use the same strategy to fight other slow transmitting tick-borne illnesses, like babeosis.
The more difficult proposition is whether his strategy can be used to fight fast transmitting tick-borne illnesses, like powassan or anaplasmosis, which are also found in Connecticut.
“They are transmitted within usually 30 minutes,” Fikrig said. “We're going to try those as well. My expectation is it will not work against those because unless the tick recognition is seconds or minutes, I don't think it will work against those.”
There is some hope, though. Longer term, Fikrig is developing a different strategy, also based on mRNA technology, to fight mosquitoborne illnesses like dengue and malaria. In that case, the method is to make the mosquito saliva less likely to infect human plasma.
If that is successful, it might mean a way to fight fast-transmitting illnesses borne by both ticks and mosquitoes.
“We're working on ways to target mosquito salivate proteins that influence the bite site to enhance plasmodium infectivity,” he said. “By blocking that we hope to reduce malaria. So we're addressing malaria, but the principle is somewhat different.”