Vaccines Against Lyme Disease are Near

ABSTRACTs & COMMENTARY

Synopsis: Two large studies of similar recombinant vaccines against Lyme disease showed efficacies of 76-92% after three doses (at 0,1, and 12 months). An FDA advisory panel has recommended RDA approval. One or more of these Lyme disease vaccines will probably be licensed soon, but many questions remain.

Sources: Steere AC, et al. Vaccination against Lyme disease with a recombinant Borrelia burgdorferi outer-surface lipoprotein A with adjuvant. N Engl J Med 1998;339:209-215; Sigal LH, et al. A vaccine consisting of recombinant Borrelia burgdorferi outer-membrane surface protein A to prevent Lyme disease. N Engl J Med 1998;339:216-222.

Two multicenter, double-blind, randomized trials over two years of 10,936 and 10,305 subjects living in areas in the United States endemic for Lyme disease were conducted using two different recombinant preparations of Borrelia burgdorferi outer surface protein A (OspA). Two vaccine doses were administered one-month apart, with a booster at 12 months. Vaccine efficacies for prevention of infection with B. burgdorferi after two doses were 49% (95% CI, 15-69%) and 68% (36-85%), and after three doses were 76% (58-86%) and 92% (69-97%). Vaccination was associated with mild, self-limited symptoms including soreness at the injection site (24% and 2%), myalgia (3% and 6%), and low-grade fever (up to 2%) during the first seven days after vaccination. There was no evidence of vaccine-associated arthritis, even in persons with prior self-reported Lyme disease, or exacerbation of neurologic conditions during 24 months of follow-up.

Comment by Hal B. Jenson, MD, FAAP

Lyme disease is the most common vector-borne disease in the United States, with 16,461 cases reported in 1996, clustered in the Northeastern coast (Massachusetts, Connecticut, Rhode Island) to the mid-Atlantic region (New York, New Jersey, Delaware, Pennsylvania, Maryland), the upper Midwest (Wisconsin and Minnesota), and northern California and Oregon. Lyme disease vaccines have been developed that induce antibodies of OspA that are lethal to B. burgdorferi in the gut of the carrier Ixodes tick while it is taking blood from a human through a bite—effectively blocking transmission of the bacterium from the tick. Antibodies of OspA are minimal or absent in persons with natural Lyme disease. The vaccine protects against the most common strains of B. burgdorferi in the United States but does not protect against all strains.

An FDA advisory panel recently recommended that the vaccine used in the first study (LYMErix, by SmithKline Beecham) be approved for use in persons 15-70 years of age in a 0, 1, and 12-month regimen with the doses given February-April, immediately preceding the peak Lyme disease season during the spring and summer.

Licensure and use of a vaccine for Lyme disease will be novel in several respects. It would be the first licensed vaccine for a vector-borne infection. It will also likely be licensed for regional use in the United States, for persons who live in endemic regions or who work in occupations that expose them to ticks. This will create many dilemmas. Persons traveling within the United States to endemic areas will be vaccine candidates, but a minimum of two doses, and preferably three doses over 12 months, are necessary to provide optimal protection.

Several concerns remain as to whether individuals with undiagnosed Lyme disease or those already suffering from chronic arthritis should receive the vaccine. It was reassuring that neither study found evidence of vaccine-associated arthritis. Neither study included persons younger than 15 years of age, despite the occurrence of one-fourth of cases of Lyme disease in children. Also, the duration of immunity is unknown. It appears that there is not long-term protection and booster doses are likely to be required, although the optimal booster regimen is unknown. Studies of the vaccine in children 4-18 years of age, and to determine the need for booster doses, are underway.

Whether an individual has received Lyme disease vaccine, it is important, especially in children, to check for ticks after outdoor activities in endemic areas. Transmission of B. burgdorferi requires more than 24 hours of tick-feeding, providing ample opportunity to interrupt transmission by frequent inspection, and removal of ticks.