Lyme disease vaccine

General information

Lyme disease is a tick-borne, spirochetal zoonosis, characterized by a distinctive skin lesion, systemic symptoms, and neurological, rheumatological, and cardiac involvement, occurring in varying combinations over a period of months to years. Borrelia burgdorferi is the causative agent in North America, whereas in Europe three genomic groups (named Borrelia burgdorferi sensu stricto , Borrelia garinii , and Borrelia afzelii ) have been identified. Endemic foci have been found in North America, Europe, the former USSR, Japan, and China. In many of these areas, Lyme disease is now the most common vector-borne disease. Because of this epidemiological problem and the severity of the disease, a vaccine was developed. High titers of antibody to outer surface protein A (OspA) of the spirochete prevented B. burgdorferi infection in mice and subsequently in immunized hamsters, dogs, and monkeys.

In December 1998, based on many prelicensure clinical trials, the first Lyme disease vaccine (LYMErix, manufactured by the then SmithKline Beecham) was licensed by the Food and Drug Administration (FDA) for individuals aged 15–70 years old [ ] and subsequently became commercially available in the USA. In 1999, the Advisory Committee on Immunization Practices (ACIP) made recommendations for Lyme disease vaccine [ ], including data on efficacy and safety [ ]. No convincing evidence was found that the vaccine caused serious problems, but discussion about its safety continued and the demand for the vaccine did not reach a sustainable level. Therefore, in February 2002 the vaccine was withdrawn by the manufacturers [ ].

In two overviews the results of various clinical and efficacy trials were summarized [ , ] and the safety, immunogenicity, and efficacy of the vaccine were underlined. The authors considered that the intravector mode of action of the vaccine was unique and opened the door to a new method of preventing insect-borne illnesses in humans.

Dr Neal Halsey, head of the Institute for Vaccine Safety at John Hopkins University, explained that the poor sales had resulted from “public misperception and the promotion of false concerns” [ ]. Lyme disease researchers consider the Lyme vaccine story in the USA to have been a setback in Lyme disease prevention. Vaccines meeting the specific epidemiological situation in Europe are under development. Lyme disease prevention and prophylaxis has been reviewed [ ].

Reports collected through the Vaccine Adverse Events Reporting System (VAERS) from December 1998 to October 2000 have been analysed to examine adverse reactions (arthritis, neuropathy, convulsions, thrombocytopenia, lymphadenopathy, flu-like syndrome, alopecia, gastrointestinal disease, and paralysis) after Lyme immunization in the adult population of the USA. Statistical methods were used to determine whether the increased incidence rates of serious adverse reactions achieved statistical significance over those reactions that were reported after Td and rubella immunizations in adults. Table 1 shows the increases in both acute and chronic adverse reactions after Lyme vaccine compared with Td vaccine [ ]. The authors also compared the incidence of arthritic reactions reported after Lyme immunization with those reported after adult rubella immunization, and found a statistical increase in the incidence of arthritic reactions after Lyme vaccine (RR = 3.4, attributable risk = 2.4, percent association = 77). There was also a statistical increase in the incidence of chronic arthritis after Lyme immunization compared with adult rubella immunization (RR = 4.8, attributable risk = 3.8, percent association = 83). Based on these results, the authors concluded that the withdrawal of Lyme vaccine from the market seems to have been justified.

Drug studies