A vaccine for Lyme disease could be on the horizon

Outdoor enthusiasts hoping to avoid catching a potentially debilitating bacterium from a tick bite could soon have another layer of defense joining bug sprays and long clothing. 

New clinical trial data from vaccine makers Pfizer and Valneva show that their Lyme disease shot reduced cases by about 70 percent compared with a placebo, the companies reported March 23 in a press release. If regulatory agencies give the vaccine, dubbed LB6V, the green light, it would help fend off Lyme disease in hikers, gardeners and others at risk for tick bites.

The results are the latest advance in the decades-long effort to develop a human vaccine for the tick-borne disease. LB6V is the first shot to make it this far on the path to approval since another vaccine was pulled from the market in 2002, in part because of low demand. 

Lyme disease, caused by Borrelia burgdorferi bacteria, is on the rise in parts of the United States, Canada and Europe. Ticks that ferry the bacteria are spreading to new areas as temperatures climb, and more are surviving the winter. In the United States alone, an estimated 476,000 people are diagnosed and treated every year. 

If approved, the new vaccine could help make a dent in the overall number of cases in people older than 5. But researchers are working to come up with other options, too, says Maria Gomes-Solecki, a microbiologist and immunologist at the University of Tennessee Health Science Center in Memphis, who has developed a vaccine for wild mice, to stop the bacteria before it gets to humans. “I am a big believer in a multipronged approach.”

The new Lyme vaccine works in ticks

Many people don’t realize that they’ve been bitten by a tick until they see the bull’s-eye rash that is a hallmark of Lyme disease. Pfizer’s and Valneva’s vaccine prevents the disease at its earliest stages by stopping ticks from transmitting Lyme bacteria through their bite. The shot trains people’s bodies to churn out antibodies that target a bacterial protein called OspA, found on B. burgdorferi’s outer shell. As ticks gorge on a vaccinated person’s blood, they also suck up antibodies that attach to OspA and prevent the bacteria from exiting the tick. 

One drawback is that “you have to maintain very high levels of antibody for [such] vaccines to work,” says Richard Marconi, a vaccinologist and microbiologist at Virginia Commonwealth University School of Medicine in Richmond. It takes four doses of LB6V to get full protection, and people might need occasional boosters to top up antibody levels on a regular basis.

The vaccine would fill a gap in preventing Lyme disease. “It’s been a generation since we’ve had a Lyme vaccine that’s been approved in the U.S.,” says Nicholas Mantis, an immunologist at the New York State Health Department’s Wadsworth Center in Albany. “These results from Pfizer and Valneva are promising.” 

The news of LB6V’s 73 percent efficacy comes with another caveat: Fewer trial participants than expected got sick, so the study did not meet its main statistical goal. Still, Pfizer and Valneva plan to submit the data to regulatory agencies in the United States and Europe that will scrutinize the data and make final decisions on approval. 

The vaccine could give people who spend time outdoors in areas where bacteria-carrying ticks are common some protection against Lyme disease. “This is not a mandatory vaccine. It’s a vaccine of choice,” Gomes-Solecki says. But because some vaccinated people might still fall ill and ticks also carry other pathogens, safeguards including bug spray, tick checks and showering after spending time outdoors remain important.

The new vaccine grew out of past lessons

LB6V grew out of work on a previous vaccine, and LB6V’s clinical trial performance is “consistent with what was observed with the one and only vaccine that has actually made it to market to date,” Marconi says. 

That older vaccine, called LYMErix, also used OspA to prevent transmission from ticks and had an efficacy of 76 percent. The U.S. Food and Drug Administration approved its use in 1998, but manufacturer SmithKline Beecham (now GlaxoSmithKline) voluntarily pulled the shot from the market in early 2002 after reports surfaced of arthritis after vaccination. 

Lyme disease can itself cause arthritis, and it was possible that the vaccine prompted the body to make antibodies that attacked both OspA and joint tissues. Follow-up studies from both the FDA and SmithKline Beecham, however, showed similar numbers of arthritis cases in both vaccinated and control groups, suggesting that the vaccine was not the cause. Lab studies also cast doubt on the link. Still, Valneva omitted from their new vaccine the part of OspA that was the purported culprit to reduce any risk.

The link between LYMErix and arthritis was never proven, but more people have become skeptical of vaccines since the early 2000s, says Marconi, who developed a Lyme disease vaccine for dogs and is working on one for people. He worries that increasing vaccine hesitancy and the need for four doses, with the possibility of boosters, could deter some people from getting vaccinated. “LYMErix was on the market before vaccine hesitancy was really starting to peak. Now we have that, and it raises the question: How successful will [LB6V] be?”

More Lyme strategies are taking shape

Although it’s unclear whether a new vaccine will be available any time soon, researchers are working to find other ways of protecting people from Lyme disease. 

Vaccines such as LYMErix and LB6V are “conceptually very attractive, because you prevent the pathogen from ever entering the body in the first place,” Marconi says. But one drawback is that B. burgdorferi bacteria have OspA on their surface only when inside a tick. Once bacteria make their way into a mammal, the protein disappears from the surface. Vaccine-built immunity can’t attack the bacteria that slip past those defenses.

Including parts of B. burgdorferi other than OspA is one way to make vaccines even more effective. The canine vaccine that Marconi and colleagues developed, for instance, includes both OspA and another protein found on the bacterium’s outer shell that sticks around in mammals. Such shots can teach the body to kill bacteria even after OspA goes away, Marconi says. 

Another drawback of LB6V is that people don’t get maximum protection immediately. Each of the four doses is given over a span of about a year and a half, and the body builds up antibodies over that time. But a dose of antibodies made in the lab would provide fast protection, Mantis says. “One shot at the beginning of the season should confer immunity for an entire tick season.” Such antibodies cost more than vaccines, Mantis notes, but could one day be an option for people who can’t wait a year for protection, such as travelers.

Some researchers such as Gomes-Solecki are aiming to hit B. burgdorferi before it makes it to the tick. In nature, ticks feeding on white-footed mice pick up and ferry the bacteria to other mammals including people. Gomes-Solecki and colleagues have tested a vaccine for those mice. The mice don’t get a physical shot. They instead feast on bait spiked with an OspA-based vaccine that stops the bacteria inside the tick. 

Field trials show that parts of Maryland with vaccinated mice end up with fewer ticks carrying the bacteria, the team reports in a paper to appear in npj vaccines. Over a span of five years, the researchers found that 43 percent fewer immature ticks in treated sites carried B. burgdorferi. The population of immature ticks capable of transmitting Lyme bacteria in untreated sites, however, more than doubled. 

“We’re not killing ticks,” Gomes-Solecki says. But as the population of infected mice gets smaller, “your likelihood of encountering a tick that is infected with Borrelia is lower.” 

Deploying many approaches at once will be key to keeping people safe. “Nature is smarter than we can ever be,” Gomes-Solecki says. Eradicating B. burgdorferi completely from mice is probably impossible. But “the more [protective] strategies you add to the entire system,” Gomes-Solecki says, “the better you are.”