As the Lyme disease epidemic began spreading across the country and more people were seriously affected by the infectious disease, two Lyme disease vaccines were developed that use outer-surface protein A (rOspA).
One was LYMErix,TM SmithKline Beecham Pharmaceuticals, and the other one was ImuLyme,TM Pasteur Merieux Connaught. Only LYMErix was licensed by the U.S. Food and Drug Administration for use in the United States.
Results of a randomized, controlled (Phase III) trial of safety and efficacy of LYMErix in persons aged 15-70 years, by those with financial stakes in the outcome, indicated that the vaccine was safe and efficacious.
Information regarding the vaccine safety and efficacy beyond the transmission season, immediately after the third dose, was not available. Thus, the duration of protective immunity and need for booster doses were never explored prior to the vaccine coming to market.
The LYMErix vaccine was administered by intramuscular injection, 0.5 mL (30 ug), into the deltoid muscle. Three doses were said to be required for optimal protection. The first dose was followed by a second dose 1 month later and a third dose administered 12 months after the first dose.
Vaccine administration had to be timed so that the second dose of the vaccine (year 1) and the third dose (year 2) were administered several weeks before the beginning of the B. burgdorferi (Lyme) transmission season. The safety and immunogenicity of alternate dosing schedules were not evaluated prior to coming to market with the vaccine.
A total of 10,936 people, aged 15-70 years, living in Lyme disease-endemic areas were recruited at 31 sites and randomized in a trial to receive three doses of vaccine or a placebo. 5,469 people received at least one 30-ug dose of rOspA vaccine, and 5,467 others received at least one injection of placebo.
They were then followed for 20 months. Information regarding adverse events that were believed to be related or possibly related to the vaccine injection were available from 4,999 subjects in each group. Doctors claimed soreness at the injection site was the most frequently reported adverse event at the time, which was reported without solicitation by 24.1% of vaccine recipients.
Redness and swelling at the injection site were reported by less than 2%, but were reported more frequently among vaccine recipients than among those who received placebo.
Myalgia, influenza-like illness, fever, and chills were more common among vaccine recipients than placebo recipients. Some reports of arthritis were documented in vaccine recipients, but they were more likely to report arthralgia or myalgia within 30 days after each dose.
The incidence of musculoskeletal symptoms within the first 30 days after vaccination was higher among vaccinees with a previous history of Lyme disease compared with vaccinees with no such history.
After infection with B. burgdorferi, persons who expressed certain MHC II molecules were more likely than others to develop chronic, poorly responsive Lyme arthritis associated with high levels of antibody to OspA in serum and synovial fluid.
In chronic Lyme arthritis patients, the levels of antibody to OspA had been found to correlate directly with the severity and duration of the arthritis. Researchers proposed that an autoimmune reaction might develop within the joints of some Lyme arthritis patients as a result of molecular mimicry between the dominant T-cell epitope of OspA and human leukocyte function associated antigen 1 (hLFA-1).
Because the association between immune reactivity to OspA and treatment-resistant Lyme arthritis is poorly understood, the vaccine should not have been administered to persons with a history of treatment-resistant Lyme arthritis.
The vaccine efficacy in protecting against "definite" Lyme disease after two doses was 49% and after three doses was 76%. In the study, "definite" Lyme disease was defined as the presence of erythema migrans (rash) or objective neurologic, musculoskeletal, or cardiovascular manifestations of Lyme disease, plus laboratory confirmation of infection by cultural isolation, PCR positivity, or WB seroconversion.
The cost-effectiveness of vaccinating against Lyme disease was analyzed from a societal perspective. At a cost of vaccination of $100/person/year, the net cost of vaccination to society was $5,692/case averted and $35,375/complicated neurologic or arthritic case avoided. Using the same baseline assumptions, the societal cost of vaccination exceeded the cost of not vaccinating.
Lyme disease vaccine did not protect all recipients against infection with B. burgdorferi and offered no protection against other tickborne diseases. Vaccinated people were told to continue to practice personal protective measures against ticks and told they should seek early diagnosis and treatment of suspected tickborne infections.
The following recommendations were made by the Centers for Disease Control (CDC) regarding use of the Lyme disease vaccine (MMWR June 04, 1999 / 48(RR07);1-17) http://www.cdc.gov/mmwr/preview/mmwrhtml/rr4807a1.htm
Lyme disease is endemic in some temperate areas of Europe and Asia; however, the CDC was unsure if the rOspA vaccine licensed for use in the United States would protect against infection with Eurasian strains.