Passive and active immunization against
outer surface protein A (OspA) has been successful in protecting laboratory animals against subsequent
infection with Borrelia burgdorferi.
Antibodies (Abs) to OspA convey full protection, but only when they are present at the time of
infection. Abs inactivate spirochetes within the tick and block their transmission 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 microg/ml) correlates with spontaneous resolution of disease and
infection in experimentally challenged immunocompetent mice suggested that therapeutic vaccination with
OspC may be feasible. We now show that polyclonal and monospecific mouse
immune sera to recombinant
OspC, but not to OspA, of B. burgdorferi resolve chronic
arthritis and
carditis and clear disseminated 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 recultivation of spirochetes from ear biopsies. Complete resolution of disease and
infection was achieved, independent of whether
OspC-specific
immune sera (10 microg
OspC-specific Abs) were repeatedly given (4x in 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 postinfection). The results indicate that in mice spirochetes constitutively express
OspC and are readily susceptible to protective
OspC-specific Abs throughout the
infection. Thus, an
OspC-based
vaccine appears to be a candidate for
therapy of
Lyme disease.