Read: Lyme disease is baffling, even to experts

Valneva’s Lyme vaccine isn’t the first designed for people. Twenty years ago, Reeder could have been immunized. From 1999 to 2002, SmithKline Beecham—now GlaxoSmithKline—sold a Lyme vaccine called LYMErix. But the company pulled LYMErix off the market after public backlash and a spate of lawsuits.

As Stat reported on August 22, any new Lyme vaccine will face intense public scrutiny. But even getting the new vaccine to market could prove challenging. Valneva is currently seeking a partner to help develop and commercialize the vaccine, and at least one major manufacturer is out of the running. GlaxoSmithKline had been supporting the new vaccine’s research and development, but in June the two companies terminated their partnership.

If the new vaccine does make it to market, will it fare any better than LYMErix? According to Gregory Poland, the director of the Vaccine Research Group at the Mayo Clinic in Rochester, Minnesota, who has given scientific advice to Valneva, that’s “a multimillion-dollar question.”

One factor that led to LYMErix’s demise was how the vaccine worked. Lyme disease, named for the Connecticut town where it was first discovered, is caused by a corkscrew-shaped bacterium called Borrelia burgdorferi that travels in the bellies of ticks. LYMErix prompted the immune system to generate antibodies against a protein on the surface of the bacteria called outer surface protein A (OspA). When a tick fed on someone who had been immunized, it ingested blood containing the Lyme-killing antibodies. Those antibodies traveled to the tick’s gut and wiped out the bacteria before they could enter the human body.

LYMErix worked, although imperfectly. A 1998 study in The New England Journal of Medicine looked at nearly 11,000 people who lived in Lyme-endemic areas and found that those who received three doses of LYMErix had a 76 percent reduction in Lyme disease the following year compared with those who didn’t receive the vaccine. But just a week after the study was published, another paper came out showing that one particular portion of the OspA gene bears a striking resemblance to a portion of a human gene that plays a role in the body’s immune response. While the second paper didn’t address vaccination, the researchers posited that because of the similarity, some people infected with Lyme disease might develop an immune response against the human protein, leading to lingering inflammation and treatment-resistant Lyme arthritis. It wasn’t a stretch to imagine that vaccination, which also prompts an immune response against OspA, might produce the same effect.

The Food and Drug Administration never found any compelling scientific evidence to support this theory, but that didn’t stop people who believed they were harmed by the vaccine from speaking out and filing a class-action lawsuit. Sales of LYMErix tanked, and in 2002 SmithKline Beecham withdrew the vaccine. The following year, the company paid more than $1 million in legal fees to settle the class-action lawsuit.