THERAPEUTIC PASSIVE VACCINATION AGAINST CHRONIC LYME-DISEASE IN MICE

Passive and active immunization against outer surface protein A (OspA) has been successful in protecting laboratory animals against subseque nt infection with Borrelia burgdorferi. Antibodies (Abs) to OspA conve y full protection, but only when they are present at the time of infec tion, Abs inactivate spirochetes within the tick and block their trans mission to mammals, but do not affect established infection because of the loss of OspA in the vertebrate host. Our initial finding that the presence of high serum titers of anti-OspC Abs (5 to 10 mu g/ml) corr elates with spontaneous resolution of disease and infection in experim entally challenged immunocompetent mice suggested that therapeutic vac cination with OspC may be feasible. We now show that polyclonal and mo nospecific mouse immune sera to recombinant OspC, but not to OspA, of B. burgdorferi resolve chronic arthritis and carditis and clear dissem inated spirochetes in experimentally infected C.B.-17 severe combined immunodeficient mice in a dose-dependent manner. This was verified by macroscopical and microscopical examination of affected tissues and re cultivation of spirochetes from ear biopsies. Complete resolution of d isease and infection was achieved, independent of whether OspC-specifi c immune sera (10 mu g OspC-specific Abs) were repeatedly given (4 x i n 3- to 4-day intervals) before the onset (day 10 postinfection) or at the time of fully established arthritis and carditis (days 19 or 60 p ostinfection). The results indicate that in mice spirochetes constitut ively express OspC and are readily susceptible to protective OspC-spec ific Abs throughout the infection. Thus, an OspC-based vaccine appears to be a candidate for therapy of Lyme disease.