Lyme Disease Vaccine Pioneered at Yale School of Medicine Shown Effective in Protecting Against the Tick-borne Illness

Two vaccines designed to protect humans against Lyme disease have been shown to be effective in tests at the Yale University School of Medicine, where one of the vaccines was pioneered and where the tick-borne illness first was described in 1975. Yale was one of many sites involved in clinical trials for the vaccines. The encouraging results were published in the July 23 issue of The New England Journal of Medicine.

The genetically engineered vaccine LYMErix*, based on discoveries by Yale researchers, prevented 49 percent of definite Lyme disease cases after two injections and 76 percent after a third injection in the second year of a study involving people between the ages of 15 and 70. Furthermore, the vaccine prevented 100 percent of cases of asymptomatic infections, which is significant because people who do not know they have been infected can develop health problems months to years later.

SmithKline Beecham has applied to the U.S. Food and Drug Administration for a license to market LYMErix*, which could make it the first Lyme disease vaccine to reach the market if approved. (SmithKline Beecham is exclusively licensed under Yale’s Lyme disease patent applications.) In May, an FDA advisory committee found the vaccine safe and effective in the population studied and recommended its approval.

According to results published this week in The New England Journal of Medicine, the second vaccine prevented 68 percent of Lyme disease cases after two injections and 92 percent after a third dose. Differences in efficacy between the two vaccines may be due to varying methods of surveillance, according to an accompanying editorial. For example, data that could be used to identify asymptomatic infections were not provided for the second vaccine.

“These two studies demonstrate that vaccination can be an important new approach to preventing Lyme disease, which is the most common tick- borne disease in the United States,” said Robert T. Schoen, M.D., clinical professor of internal medicine at the Yale School of Medicine and a member of the team that studied LYMErix*. Yale rheumatologist Erol Fikrig, M.D., one of the pioneers of a vaccine, also was a member of the research team.

In addition to enrolling and vaccinating volunteers in the trials, Yale researchers performed the immunogenicity tests required to measure the level of antibodies formed in response to vaccination. Yale researchers now are participating in a trial of LYMErix* to determine the need for booster doses.

Yale has assembled one of the largest concentrations of Lyme- disease researchers in the world. Over the past two decades, the contributions of Yale researchers have included not only identifying Lyme disease but tracking the spread of the disease and determining the usefulness of antibiotics in treating it. Researchers affiliated with Yale’s Lyme Disease Consortium have authored more than 200 papers on the disease and related topics.

“Yale has made a major commitment to combating Lyme disease through diagnosis, treatment, and now also prevention,” said Dr. Schoen. “That commitment clearly is producing a benefit for public health.”

Lyme disease is transmitted by ticks infected with the bacterium Borrelia burgdorferi. People with the infection often develop a rash known as erythema migrans, which may be accompanied by headache, fever, fatigue, and muscle and joint aches. The most serious cases may result in neurological disorders, arthritis or heart problems.

Yale Professor Stephen E. Malawista, M.D., and research fellow Allen C. Steere, M.D., identified the disease in 1975 after mothers in Lyme, Conn., insisted that an infectious agent was responsible for the arthritic swelling of their children’s joints. Dr. Malawista, a member of the team reporting this week on the second vaccine, showed in 1980 that antibiotics almost always cure the disease in its early stages and are usually effective in later stages as well.

Cases of Lyme disease have been reported in 48 states with 16,461 cases reported to the Centers for Disease Control and Prevention in 1996 alone. The population at greatest risk includes people who engage in outdoor activities in the endemic areas of New England, the mid- Atlantic states, the upper Midwest and the Pacific Northwest.

The study of LYMErix*, which extended over two Lyme- disease seasons, enrolled 10,936 people at 31 medical sites in 10 states. Cases of definite Lyme disease comprised both characteristic symptoms and laboratory confirmation of B. burgdorferi infection; asymptomatic infection was determined by laboratory confirmation only. More than 20,000 people were enrolled altogether in the double-blind studies of both vaccines, with about half randomly assigned to receive a vaccine while the other half received a placebo.

Comprehensive serological testing (Western blot) was performed to measure protection with LYMErix* against both symptomatic and asymptomatic infection. Culture and polymerase chain reaction (PCR) also were performed to identify cases of Lyme disease which would have been missed by serological tests alone.