A reader responds to Wednesday’s post on the growing numbers of Lyme disease infections (“Finding Truth in a Tick Bite”) by asking:
I heard that there was a vaccine developed years ago but it was abandoned. What is the current status on a vaccine?
Dog owners might know that a Lyme disease vaccine is available for their pooches, but few of us remember that there was once a vaccine that was licensed to protect people from the Borellia burgdorferi bacteria transmitted by a deer tick bite. To learn more, we need to study The History of Vaccines:
The first and only licensed vaccine against Lyme disease was developed by SmithKline Beecham (now GlaxoSmithKline). Given in a three-dose series, the vaccine had an unusual method of action: it stimulated antibodies that attacked the Lyme bacteria in the tick’s gut as it fed on the human host, before the bacteria were able to enter the body. This was about 78% effective in protecting against Lyme infection after all three doses of the vaccine had been given.
The vaccine, called LYMERix, was licensed in 1998. By 2002 SmithKline Beecham had withdrawn it from the market, and Pasteur Mérieux Connaught decided not to apply for a license for its own Lyme vaccine candidate, despite having already demonstrated its efficacy in a Phase III clinical trial. Today there are no vaccines available to prevent Lyme disease, and it is unlikely that any will be licensed in the near future. The debut and subsequent withdrawal of the Lyme disease vaccine has lasting implications for future vaccine development and use.
Market forces, according to the National Institutes of Health (NIH), were the primary reasons for bringing LYMErix down:
In April 2002, GSK announced that even with the incidence of Lyme disease continuing to rise, sales for LYMErix declined from about 1.5 million doses in 1999 to a projected 10,000 doses in 2002. Although studies conducted by FDA failed to reveal that any reported adverse events were vaccine-associated, GSK discontinued manufacturing the vaccine.
Pediatrician Stanley A. Plotkin remembers things differently; LYMErix was doomed from the start:
In 1998 SmithKline Beecham (now GlaxoSmithKline) developed a vaccine that was about 80 percent effective for at least a year after three doses. But the Advisory Committee on Immunization Practices, which counsels the C.D.C. on vaccine use, was lukewarm about the real benefits and necessity of it. The committee made a weak recommendation to “consider” vaccination for high-risk persons, overlooking the fact that plenty of casual gardeners and hikers were being infected. Instead, the committee emphasized the use of protective clothing and insect repellents, despite little evidence that those measures prevent tick bites and even less evidence that people will constantly use them.
Nevertheless, the vaccine was put on the market and physicians had to decide what to do with the ambiguous recommendations. Then the manufacturer made a strategic error of its own, deciding to directly advertise the vaccination to the public, despite the fact that by and large people rely on their doctors’ recommendations to decide whether to receive a vaccine. In addition, the manufacturer put the vaccine on the market before it had been tested in children, so it could be prescribed only to adults.
The final straw leading to LYMErix’s withdrawal from the market, despite increased infections, serves as a cautionary tale for why, 13 years later, we haven’t seen another Lyme disease vaccine developed and marketed (and why it’s so hard to get vaccines for other diseases researched, developed, and into the pipeline):
But the biggest blow to the marketing campaign came from a group of volunteers who had been involved in the vaccine’s prelicensure studies and who reported developing arthritic symptoms after the vaccination. Although the rate of arthritis in the vaccinated volunteers was the same as the rate in the control group, some Lyme disease activists concluded that the vaccine caused, rather than prevented, Lyme disease. In 1999, a class-action suit was brought against the manufacturer. Retrospective studies have shown no connection between the vaccination and arthritis, but at the time, sales of the vaccine dropped precipitously, and in 2002 the manufacturer withdrew it from the market.
In an article reviewing the factors leading to LYMErix’s demise, Dr. Gregory A. Poland expressed his pessimism regarding development of a new Lyme disease vaccine in the journal Clinical Infectious Diseases in 2011:
The factors mentioned above conspire to create an unfavorable scientific, cultural, legal, and economic environment for the future development of a vaccine against Lyme disease. Although there has been variable and sporadic interest among manufacturers outside of the United States in developing such a vaccine, this interest has not been sustained and has not led to additional significant research to the point of developing a vaccine candidate ready for large-scale clinical trials.
Yet two years later came news of a new Lyme disease vaccine on the horizon. By summer 2013, a study in Europe was completing its initial phases:
The research team consisted of scientists from Stony Brook University, Brookhaven National Laboratory, and Baxter International Inc. They analyzed the safety and immune response potential of the vaccine in a range of doses among 300 people living in Germany and Austria.
Study volunteers received three primary immunizations and one booster. All types and doses – some of which had an adjuvent, an additive that triggers an immune response to the vaccine – resulted in significant antibodies against all species of Borrelia.
The vaccine caused mostly mild adverse reactions. No-vaccine induced serious events were documented in the sample population.
And that’s where the trail for a new Lyme disease vaccine goes cold. By 2014, Baxter was divesting itself of vaccine research and development and no one, apparently, had an interest in picking up on the promising research. Even Stony Brook University has very little to say about further research on the new vaccine they were studying, though they do mention an effort from the University of Tennessee to target the white-footed mouse — a rodent believed to be the reservoir of Borellia burgdorferi:
A pellet-sized vaccine called the Reservoir Targeted Vaccine was developed based on the outer surface protein A (OspA) of the bacteria. This bacteria triggers an immune response in the mice. Infection rates among ticks that were baited and not baited were recorded, and the reductions of infected ticks in the baited area ranged from 23-76%. The pellet was not associated with any harm to the environment. This vaccine seems promising and also seems like it is on its way to hitting the market.
Dogs and mice are pretty lucky; humans, who had a good vaccine going 13 years ago, not so much.