Lyme Disease Vaccine Pioneered by Yale Researchers, Developed by SmithKline Beecham, Receives FDA Approval

Yale School of Medicine
Tuesday, 22 December 1998

LYMErix* Becomes First Lyme Disease Vaccine on the Market

LYMErix*, pioneered by Yale University researchers and manufactured by SmithKline Beecham Biologicals, has received approval from the U.S. Food and Drug Administration (FDA) for the prevention of Lyme disease.

LYMErix*, the world's first vaccine to prevent Lyme disease, has been proven effective in the prevention of both definite Lyme disease (characteristic symptoms with serologic diagnosis) and asymptomatic infection (no symptoms, but serologic diagnosis of infection).

Lyme disease is a tick-borne illness first described in 1975 by Yale researchers. An emerging infectious disease, it is a potentially serious multi-stage bacterial infection with a wide range of symptoms -- from a characteristic skin rash and flu-like symptoms to arthritis and heart abnormalities.

The approval of LYMErix* is welcome news for people who live in or travel to tick-infested areas, or people who enjoy outdoor activities in these areas. Lyme disease has rapidly become the most common tick-borne illness, with cases reported in 48 U.S. states. More than 99,000 cases have been reported to the Centers for Disease Control and Prevention from 1982 to 1996.

People at highest risk include those living in, working in or traveling to endemic areas in the Northeast, upper Midwest and Pacific coastal areas. According to a recent study published in Clinical Therapeutics, the economic burden of Lyme disease in the United States is projected to be $2.5 billion in direct and indirect medical costs over a five-year period.

LYMErix* was evaluated in a landmark clinical trial that enrolled 10,936 individuals ranging from 15 to 70 years of age at 31 U.S. sites, including Yale University. Results from the multi-center, double-blind, placebo-controlled clinical trial demonstrated vaccine efficacy rates of 78 percent against definite Lyme disease and 100 percent against asymptomatic infection after three doses (after two doses, vaccine efficacy rates were 50 and 83 percent, respectively). Study participants received three doses of LYMErix* or placebo on a 0, 1 and 12 month schedule. Compliance in the study was high, with 95 percent of participants completing the 20-month study.

"This action by the FDA is an important milestone in the prevention of Lyme disease,'' said Eddie Gray, vice president and director, SmithKline Beecham's U.S. Vaccine Business Unit. "The approval of LYMErix* means the threat of Lyme disease may be significantly reduced for millions of Americans who spend time outdoors or plan to travel to endemic areas.''

LYMErix* is a genetically engineered vaccine that contains lipoprotein OspA, an outer surface protein of the Lyme disease bacterium, Borrelia burgdorferi. A novel hypothesis has been proposed to explain the effectiveness of lipoprotein OspA vaccination: When infected ticks bite humans who have been vaccinated with LYMErix*, the vaccine-induced antibodies are taken up by the tick and interact with the Borrelia burgdorferi in the midgut of the tick, thereby preventing transmission of the organism to the host.

LYMErix* may be associated with local injection-site reactions including redness and swelling, flu-like symptoms, arthralgias and myalgias. The vaccine should be available within weeks. For more information on Lyme disease and LYMErix*, call toll-free 1-888-LYMERIX, ext. 500.

Lyme Disease: A Widespread and Potentially Debilitating Disease
Lyme disease is a multi-stage disease caused by infection with a spiral- shaped bacterium (called a spirochete) known as Borrelia burgdorferi, which is carried by ticks that transmit the infection from animals to humans. Experts believe Lyme disease may be underreported by as much as 12 times (Maryland). In Connecticut, data indicate that, at best, only 16 percent of Lyme disease cases were reported over one year.

The onset of Lyme disease is commonly associated with a characteristic skin rash known as erythema migrans (EM), which can vary in size and location. EM is often accompanied by flu-like symptoms including headache, fever, fatigue, joint aches, muscle aches and a stiff neck. When diagnosed early, Lyme disease can usually be successfully treated with antibiotics without any long-lasting complications. However, diagnosis can be difficult because symptoms may imitate other illnesses.

If undetected and left untreated, the Lyme bacteria can spread to other parts of the body months to years following a tick bite and progress to late-stage Lyme disease. The bacteria can affect the joints, tendons, heart or nervous system, potentially resulting in arthritis, heart abnormalities such as heart block and myocarditis (inflammation of the muscular walls of heart) and Bell's palsy (paralysis of one or both sides of the face). Previous infection with Borrelia burgdorferi may not confer protective immunity. Therefore people with a prior history of Lyme disease may benefit from vaccination with LYMErix*.

In addition to getting vaccinated, people can decrease their risk by avoiding tick-infested areas, tucking in pants and shirts, wearing light-colored clothing to spot ticks, using insect repellent containing DEET and checking family members and pets for ticks.

* Trademark (TM) ** or Richard Koenig, SmithKline Beecham, (215) 751-3415

Timeline of Lyme Disease Discoveries at Yale University

Yale School of Medicine researchers first identified Lyme disease 23 years ago, and another team of Yale researchers more recently pioneered a vaccine to prevent the debilitating tick-borne disease. The vaccine, which is called LYMErix*, is based on Yale discoveries and is being marketed by SmithKline Beecham. It was approved Dec. 21, 1998, by the Food and Drug Administration, making it the first vaccine for Lyme disease to reach the market. (SmithKline Beecham is exclusively licensed under Yale's Lyme disease patent applications).

During the past two decades, Yale has assembled a Lyme disease dream team of 20 advanced investigators and clinicians -- the largest and arguably the finest concentration of Lyme disease researchers anywhere in the world. Yale's Lyme Disease Consortium, established in 1991, has emerged as the foremost center for Lyme disease research and treatment.

The consortium's efforts have focused on exquisitely precise basic research into the activities of the bacteria that cause the disease and the body's response to them as well as on public health initiatives, including the study and control of the carrier deer tick in its natural woodlands habitat.

Advances have included:

1975 Yale Professor Stephen E. Malawista, M.D., and research fellow Allen C. Steere, M.D., identify the disease after mothers in Lyme, Connecticut, insist that an infectious agent is responsible for the arthritic swelling of their children's joints.

1975-1980 Malawista and Steere, along with their colleagues, describe the disease's natural history, epidemiology, and immunopathology.

1980 Malawista and Steere show that antibiotics almost always cure the disease in its early stages. They subsequently show that later stages usually are curable as well.

1983 First biennial international conference hosted by Yale (last held in 1996 in San Francisco) for educating medical professionals and the public.

1986-88 Mouse model for Lyme disease, which was developed at Yale, still is the most widely used for basic research.

1989 Erol Fikrig, M.D.; veterinarian Stephen Barthold; Fred S. Kantor, M.D.; and Richard A. Flavell, Ph.D., discover potential Lyme disease vaccine at Yale.

1991 Yale's Lyme Disease Consortium founded. The National Institutes of Health, G. Harold and Leila Y. Mathers Charitable Foundation, Arthritis Foundation, Community Foundation of Greater New Haven and Eshe Foundation of New York are among funding sources for Yale's Lyme disease research over the years.

1992-1998 Researchers affiliated with Yale's Lyme Disease Consortium author more than 300 papers on the disease and related topics.

1994-1997 Vaccine (LYMErix*) undergoes clinical trials in humans to establish safety and efficacy.

1995 Number of reported cases in the Northeast declines 30 percent, mostly through public education. The disease is still prevalent, with 13,000 cases reported annually in the United States. Although reported in 48 states as well as Europe and Asia, 80 percent of the U.S. cases occur in just 10 counties.

1996-1998 Epidemiologist Durland Fish, Ph.D., tracks spread of the disease worldwide by satellite. A total of 16,461 cases are reported to the Centers for Disease Control and Prevention in 1996.

1997 Two rare, sometimes fatal forms of tick-borne diseases -- human granulocytic ehrlichiosis and babesiosis -- reportedly are on the rise. Both are treatable.

1998 Yale develops sensitive technologies to test for Lyme disease in the blood more accurately and establishes new clinical reference laboratory, L2 Diagnostics, to make them available to the public.

Dec. 26, 1998 LYMErix* vaccine approved by FDA.

For more information, or to contact Yale School of Medicine, see their website at: info.med.yale.edu/ysm/