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Lyme Vaccine Lymerix Leaves Market, but Others in Wings

Borrelia burgdorferi, the causative agent of Lyme disease. (© Jeffrey Nelson, author. Licensed for use, ASM MicrobeLibrary.)

Drug and vaccine producer GlaxoSmithKline quietly pulled Lymerix, the only U.S.-licensed vaccine for preventing Lyme disease, from the market last February, citing poor sales and shrinking demand. Critics of that vaccine contend that its use caused odd and damaging side effects, while several researchers who are developing alternative vaccines say that different approaches will be needed to protect individuals against a broader spectrum of this and other insect-borne infectious diseases.

A few days before GlaxoSmithKline dropped Lymerix, representatives of the Lyme Disease Association (LDA) and International Lyme and Associated Disease Society (ILADS) met with officials from the Food and Drug Administration (FDA) to express concerns about the vaccine's safety. These events represent "an interesting series of coincidences," says LDA president Patricia Smith, whose organization is based in Jackson, N.J.

When Lymerix was released in 1999, "we were neither for or against it," Smith says. She and others from LDA and ILADS presented evidence to FDA officials indicating that numerous individuals experienced adverse reactions, including joint and muscle pain, after receiving the vaccine. In others with Lyme disease who were treated with antibiotics and later received the vaccine, its use appeared to trigger a return of Lyme symptoms, such as fatigue or memory loss, she says. However, when patients complained of such side effects, many of them were told that the symptoms were not related to the vaccine. Hence, few reports were sent into the federal Vaccine Adverse Events Reporting System (VAERS).

The active antigen in Lymerix is a major outer surface protein, OspA, from Borrelia burgdorferi, the spirochete that causes Lyme disease via tick bites. Noting that OspA sometimes causes autoimmune reactions when administered to animals, LDA representatives warned officials at FDA and GlaxoSmithKline that the vaccine might trigger similar responses in humans and might also produce other adverse effects among individuals with subclinical cases of Lyme disease. "Unfortunately, these concerns have come home to roost," Smith says. The two main complaints among vaccine recipients are reactions similar to rheumatoid arthritis, an autoimmune disease, and the development of Lyme disease symptoms among otherwise asymptomatic individuals.

The abrupt removal of Lymerix from the market surprised infectious disease specialist Benjamin Luft, Chairman of Medicine at the State University of New York at Stony Brook. Moreover, the events and accusations about its safety that preceded its removal "do not serve the vaccine world very well," he says. For example, many of the adverse reactions attributed to the vaccine are based on anecdotal accounts from patients whose claims did not reach VAERS. "There's confusion over why the reporting system broke down," says Luft, and the "controversy needs clarification to prevent stigmatizing other vaccines."

Luft, who is developing a multivalent vaccine to protect recipients against Lyme disease, says that simpler vaccine formulations, such as Lymerix, "with a single protein won't work." To be effective, he explains, vaccines need to be designed to protect against a variety of Borrelia species that spread Lyme disease worldwide. Hence, he and his collaborators are engineering a vaccine with broad specificity containing epitopes from various Borrelia species. The current experimental vaccine protects animals from Lyme infection when challenged with tick species carrying Borrelia varieties from the United States and Europe. However, the experimental vaccine that Luft described earlier this year in The Journal of Infectious Diseases [105(Suppl.):S46-S51, 2002] is several years away from being tested in humans.

Stephen Wikel, director of the Center for Microbial Pathogenesis at the University of Connecticut in Farmington, received $2.5 million from the Department of Defense in January 2002 to explore an even broader approach to developing a vaccine to protect against Lyme disease. Researchers in Wikel's laboratory and colleagues in the U.S. Navy find that blocking key molecules in saliva of insect vectors prevents transmission of Borrelia or other pathogens responsible for causing diseases in humans whom such insects bite. Rather than needing individual vaccines to target each pathogen, the saliva-based method may prevent blood-feeding insects from spreading bacteria, viruses, and other pathogens.

Tick saliva contains a range of molecules, including anticoagulants, modulators of the immune response, and inhibitors of adhesion. These factors help ticks circumvent defense responses of the animals, including humans, upon which they feed. "It's really remarkable how ticks have taken on hemostasis and the innate immune system," says Wikel, who reviewed several of these complex defense-undermining mechanisms late last year [Ann. Trop. Med. Parasitol. 95:755-771, 2001]. Ideally, a vaccine could be designed to carry a mix of factors that block the greatest number of diseases spread by ticks. "It's not exactly one-size-fits-all, but one-size-fits-many," Wikel says. In Lyme disease, he adds, the infectious agent is not transmitted until the tick has fed for at least 24 hours, so counteracting saliva components early on "could make a big difference."

Carol Potera
Carol Potera is a freelance writer in Great Falls, Mont.