Recommendations for the use of the Lyme disease vaccine (Lymerix) have been issued by the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC). The recommendations were reported in the June 4, 1999, issue of Morbidity and Mortality Weekly Report (vol. 48, no. RR-7).
In addition to information about the vaccine, the report includes a discussion of the epidemiology, clinical features, diagnosis, treatment and prevention of Lyme disease. An appendix to the report shows how Lyme disease risk is measured as a function of entomologic risk and human exposure.
According to the CDC, the number of cases of Lyme disease reported annually in the United States has increased 25-fold since national surveillance of the disease began in 1982. From 1993 through 1997, a mean of 12,451 cases were reported annually to the CDC. Cases occur primarily in the northeastern United States, the mid-Atlantic region, the upper north-central United States (mainly Wisconsin) and in several areas in northwestern California.
The ACIP recommendations for the Lyme disease vaccine are summarized in the accompanying table. According to ACIP, the decision to administer the vaccine should be based on the individual's risk of being bitten by an infected tick. Risk assessment includes consideration of the geographic distribution of Lyme disease and the person's risk of prolonged exposure to the habitat of infected ticks.
|Persons who reside, work or recreate in areas of high or moderate risk|
|Persons 15 to 70 years of age whose exposure to tick-infested habitat is frequent or prolonged||Should be considered|
|Persons 15 to 70 years of age who are exposed to tick-infested habitat, but whose exposure is not frequent or prolonged||May be considered|
|Persons whose exposure to tick-infested habitat is minimal or none||Not recommended|
|Persons who reside, work or recreate in areas of low or no risk||Not recommended|
|Travelers to areas of high or moderate risk|
|Travelers 15 to 70 years of age whose exposure to tick-infested habitat is frequent or prolonged||Should be considered|
|Children <15 years of age||Not recommended|
|Persons >70 years of age||No available data|
|Pregnant women||Not recommended|
|Health care providers are encouraged to register vaccinations of pregnant women by calling SmithKline Beecham Pharmaceuticals at 800-366-8900, x 5231|
|Persons with immunodeficiency||No available data|
|Persons with musculoskeletal disease||Limited data available|
|Persons with previous history of Lyme disease|
|Persons 15 to 70 years of age with previous uncomplicated Lyme disease who are at continued high risk||Should be considered|
|Persons with treatment-resistant Lyme arthritis||Not recommended|
|Persons with chronic joint or neurologic illness related to Lyme disease and persons with second- or third-degree atrioventricular block||No available data|
|Vaccine schedule: Three doses administered by intramuscular injection—initial dose, followed by a second dose one month later, followed by a third dose 12 months after the first dose. Administer the second dose (year 1) and third dose (year 2) several weeks before the beginning of the disease transmission season, which is usually April.|
|Boosters: Existing data indicate that boosters might be needed, but additional data are required before recommendations can be made regarding booster schedules.|
|Simultaneous administration with other vaccines: Additional data needed; if simultaneous administration is necessary, use separate syringes and separate injection sites.|
The following highlights the information on the mechanism of action, safety, efficacy and immunogenicity of the Lyme disease vaccine.
Mechanism of Action
The Lyme disease vaccine uses recombinant Borrelia burgdorferi lipidated outer-surface protein A (rOspA) as immunogen. Each 0.5-mL dose of the vaccine contains 30 μg of purified rOspA lipidated protein.
Studies in animals indicate that B. burgdorferi in a vector tick undergoes substantial antigenic change between the time of tick attachment on a mammalian host and subsequent transmission of B. burgdorferi to the host. Spirochetes residing in the tick gut at the beginning of tick feeding express primarily OspA. As tick feeding ensues, the expression of outer-surface protein C (OspC) is increased, and the expression of OspA is decreased. Thus, spirochetes that reach the mammalian host after passing through the tick salivary glands express primarily OspC. The vaccine might exert its principal effect by eliciting antibodies that kill Lyme disease spirochetes within the tick gut.
A randomized, placebo-controlled phase 3 trial included 10,936 subjects who ranged from 15 to 70 years of age and lived in areas where Lyme disease is endemic. The subjects were recruited at 31 sites; 5,469 received at least one 30-μg dose of the vaccine, and 5,467 received at least one placebo injection. Follow-up lasted 20 months.
The most frequent adverse event was soreness at the injection site, which was reported in 24.1 percent of the vaccine recipients. Fewer than 2 percent of the subjects in the vaccine group and the placebo group reported redness and swelling at the injection site. Myalgia, influenza-like illness, fever and chills were more commonly reported by vaccine recipients than placebo recipients, but no more than 3.2 percent of the subjects reported these symptoms. No statistically significant difference was noted between the vaccine and placebo recipients in the incidence of adverse events more than 30 days after a vaccine administration. No differences in the incidence of neurologic or rheumatologic disorders were found among vaccine and placebo recipients during the 20 months of follow-up.
The phase 3 trial also showed that the incidence of adverse events among vaccine recipients who were seropositive at baseline was similar to that among those who were seronegative. In addition, evaluation of safety in 30 patients with a history of Lyme disease revealed no serious adverse events. The safety of three different dosage strengths was evaluated in this uncontrolled safety and immunogenicity trial.
Efficacy and Immunogenicity
Vaccine efficacy (i.e., protection against “definite” Lyme disease) in the phase 3 trial was 49 percent after two doses and 76 percent after three doses. (Definite Lyme disease was defined as the presence of erythema migrans or objective neurologic, musculoskeletal or cardiovascular manifestations of Lyme disease, plus laboratory confirmation of infection.) Efficacy in protecting against asymptomatic infection (i.e., Western immunoblot seroconversion) was 83 percent in the first year and 100 percent in the second year.
Immunogenicity was studied in a group of the adult subjects in the phase 3 clinical trial. One month after the second dose, the geometric mean antibody titer (GMT) of IgG anti-OspA antibodies was 1,227 ELISA units per mL. Ten months later, the GMT had declined to 116 ELISA units per mL. One month after the third injection (month 13), the mean GMT was 6,006 ELISA units per mL, which then declined to 1,991 ELISA units per mL by month 20. Data from the manufacturer indicate that a titer of more than 1,200 ELISA units per mL confers protection against Lyme disease.