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Two schools of thought reign, according to Tulane's Embers: On the one hand, there are doctors who say that Lyme symptoms will persist in some patients even after antibiotic treatment, and that will lead to chronic Lyme. (In other words, there's an active infection. A study published in 2018 found "persistent Borrelia infection despite antibiotic therapy in patients with ongoing Lyme disease symptoms.") On the other hand, some medical professionals argue that antibiotics always treat Lyme symptoms, and therefore any lingering issues a patient has afterward must be due to something else.

Still, science can agree on one thing: not contracting Lyme disease in the first place is best. To that end, some scientists have mobilized to tackle the Lyme problem by flipping the script. Forget treating Borrelia in the body. What if you could immobilize it while it was still inside the tick?

Enter Mark Klempner. A physician and infectious-disease scientist at the University of Massachusetts, he's embarked on an experiment that could upend the field of Lyme treatment. Klempner is the lead creator of a first-of-its-kind antibody shot for preventing Lyme infection. The idea is to administer the injection annually, so that people are protected from late spring through early fall.

Bespectacled and friendly, Klempner, now in his early seventies, has a reassuring air about him. He comes across as insatiably curious, the product of a life spent trying to unravel medical conundrums.

A trip to Nigeria in 1972 decided the trajectory of his career in health care. While working in a field hospital, he treated patients with malaria, measles, and tuberculosis. When he graduated from Cornell University Medical College in 1973, he knew he wanted to study infectious diseases. In his third year of medical school he applied for a fellowship at the NIH, at the encouragement of the college's chief resident, Anthony Fauci. (You may have heard of him.) Klempner arrived for a three-year stint in 1975--the same year that juvenile arthritis was first reported in Lyme, Connecticut.

"I spent quite a bit of time looking at the host response to infectious agents, so I knew a lot about how the body fought off infections," he says. "Then came Lyme disease, and nobody knew how your body fought it off."

Klempner spent years researching Lyme disease. He even took a summer sabbatical in 1990 to work with Burgdorfer at Rocky Mountain Laboratories in Montana, where the pioneering studies on Borrelia took place. Klempner went on to head up MassBiologics, the country's only nonprofit vaccine manufacturer licensed by the Food and Drug Administration. (In July, he transitioned from that role into one that focuses on the clinical development of medicines in the nonprofit's pipeline.) Having learned how the body fights Lyme, Klempner turned his attention, in 2014, to coming up with a preventative medication.

The Lyme microbe is a tough adversary, with a wide reach. There are 18 known species of Borrelia across North America, Europe, and Asia that cause Lyme disease. But it does have a weakness, which Klempner aimed to exploit: the bacterium's exterior is covered with outer surface proteins that govern its behavior. Outer surface protein A (OspA) coats the microbe while it's inside the tick, allowing it to stick to the gut walls. Once the tick bites someone and starts drinking blood, microbes slowly shed OspA in favor of outer surface protein C (OspC), which helps the bacteria move from the gut to the salivary glands and, from there, to the bloodstream, where this new protein jacket further helps it evade the human immune system.

Klempner's idea was simple: find an antibody that neutralizes OspA, spin it up into an injectable solution, and inoculate someone. The discovery and development involved a host of scientists and clinicians from MassBiologics and elsewhere. Called Lyme PREP (for "pre-exposure prophylaxis"), the treatment delivers many identical Lyme-microbe-fighting antibodies directly into the bloodstream. (It's the same sort of monoclonal antibody approach that's used to treat some COVID-19 patients.) When a tick latches on and starts drinking, it sucks the antibodies right into its gut, stopping Borrelia bacteria. "You're trying to block transmission before you even get the bacteria in you," Klempner says.

At its highest dosage, Lyme PREP was 100 percent effective in mice and nonhuman primates. (Embers actually helped Klempner and his team conduct studies on nonhuman primates in Massachusetts.) Still, that's no guarantee of crossover success in people. Mice are carriers of Lyme microbes, and yet they don't get sick from the infection. And while primates are our close mammalian cousins, they're just a substitute for the real test. Earlier this year, Lyme PREP entered its first clinical trials in humans.

A decade ago, 300,000 Americans would contract Lyme in a year. Now, with numbers rising, and because of how tricky the disease is to eradicate in some people, a pre-Lyme treatment that works well could be huge. "It's pretty well accepted that the longer the infection goes, the more difficult it is to treat," Embers says. "If we can prevent infection, that would really be a game changer."

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