A total of 10,000 new cases of Lyme disease are reported each year to the Centers for Disease Control and Prevention, making it the most common vectorborne disease in the United States. Steere and colleagues, of the Lyme Disease Vaccine Study Group, report the results of a multicenter, randomized, double-blind, placebo-controlled phase III trial of a vaccine for the prevention of Lyme disease.
The 10,936 subjects were enrolled in the study at 31 sites in 10 states in which Lyme disease is endemic. The mean age of the study participants was 46 years (range: 15 to 70 years). Immunization against Lyme disease consisted of three injections of recombinant Borrelia burgdorferi outer-surface lipoprotein A (OspA) with adjuvant. Two additional injections were administered one month and 12 months later. Patients were excluded if they had active Lyme disease or were treated for Lyme disease within three months before the study began.
Blood samples for measurement of antibody to B. burgdorferi were drawn at baseline and again two, 12 and 20 months later. Only Western blot testing was performed because enzyme-linked immunosorbent assay would likely yield positive results in patients who received the Lyme disease vaccine. Serologic evidence for the diagnosis of Lyme disease was based on the demonstration of seroconversion between baseline and the acute phase of the illness or between the acute phase and convalescence.
Participants were asked to notify the investigative site if they developed any symptoms suggestive of Lyme disease. Cultures and laboratory tests for B. burgdorferi DNA by polymerase chain reaction (PCR) were performed on biopsy specimens from erythema migrans lesions. PCR testing was also done on joint fluid or cerebrospinal fluid if the test was clinically indicated.
During the first year after vaccination, 1,109 subjects were evaluated for possible Lyme disease, and in 89 percent, other diagnoses were made. During the second year, 808 subjects were evaluated for possible Lyme disease, and 82 percent were diagnosed with an illness other than Lyme disease. In both years, a diagnosis other than Lyme disease was made in nearly an equal number of subjects in the placebo and the vaccine groups.
In the first year, after two injections, 22 subjects in the vaccine group and 43 subjects in the placebo group had definite Lyme disease. The vaccine efficacy was calculated to be 49 percent after two injections. In the second year, after the third injection, 16 subjects in the vaccine group and 66 subjects in the placebo group contracted Lyme disease, which translates to a vaccine efficacy of 76 percent.
During the first year, two subjects in the vaccine group and 13 subjects in the placebo group had asymptomatic IgG seroconversion. However, in the second year, 15 placebo recipients had asymptomatic IgG seroconversion compared with none of the subjects in the vaccine group. This translates to a vaccine efficacy of 83 percent in the first year and 100 percent in the second year in this subset of participants.
Evaluation of antibody responses to the protective epitope of OspA demonstrated that 95 percent of the recipients had measurable antibody titers one month after the second injection. After the third injection, 99 percent had measurable antibody titers.
Adverse effects such as redness, swelling and soreness at the injection site and myalgias, aches, fever or chills were reported by 63 percent of the vaccine recipients and 53 percent of the placebo recipients. The symptoms tended to occur within 48 hours of vaccination and lasted about three days.
The authors conclude that three injections of the Lyme disease vaccine induced a high level of protective antibody against B. burgdorferi infection. The authors believe this vaccine is an important step in the prevention of Lyme disease.