Evaluation of the Borrelia burgdorferi BBA64 protein as a protective immunogen inmice.

摘要

The Borrelia burgdorferi bba64 gene product is a surface-localized lipoproteinsynthesized within mammalian and tick hosts and is involved in vectortransmission of disease. These properties suggest that BBA64 may be a vaccinecandidate against Lyme borreliosis. In this study, protective immunity against B.burgdorferi challenge was assessed in mice immunized with the BBA64 protein. Micedeveloped a high-titer antibody response following immunization with solublerecombinant BBA64 but were not protected when challenged by needle inoculation ofculture-grown spirochetes. Likewise, mice passively immunized with an anti-BBA64 monoclonal antibody were not protected against needle-inoculated organisms.BBA64-immunized mice were subjected to B. burgdorferi challenge by the naturalroute of a tick bite, but these trials did not demonstrate significant protectiveimmunity in either outbred or inbred strains of mice. Lipidated recombinant BBA64produced in Escherichia coli was assessed for possible improved elicitation of a protective immune response. Although inoculation with this antigen produced ahigh-titer antibody response, the lipidated BBA64 also was unsuccessful inprotecting mice from B. burgdorferi challenge by tick bites. Anti-BBA64antibodies raised in rats eradicated the organisms, as evidenced by in vitroborreliacidal assays, thus demonstrating the potential for BBA64 to be effective as a protective immunogen. However, passive immunization with the samemonospecific rat anti-BBA64 polyclonal serum failed to provide protection againsttick bite-administered challenge. These results reveal the challenges faced innot only identifying B. burgdorferi proteins with potential protective capabilitybut also in producing recombinant antigens conducive to preventive therapiesagainst Lyme borreliosis.