CIRCUMVENTION OF OUTER SURFACE PROTEIN-A IMMUNITY BY HOST-ADAPTED BORRELIA-BURGDORFERI

Outer surface protein A (OspA), which is abundantly expressed in cultu red Borrelia burgdorferi, appears to be down-regulated or masked follo wing low dose infection, and OspA immunization did not prevent infecti on, dissemination, or disease development with host-adapted spirochete s. Seroconversion of mice to B. burgdorferi OspA depended on dose and viability of inoculated spirochetes. Mice inoculated with >10(4) live spirochetes and >10(7) heat-killed spirochetes seroconverted to OspA, but mice inoculated with fewer spirochetes did not seroconvert to OspA at 2 weeks after inoculation. Growth temperature of spirochetes was n ot a factor for infectious dose or seroconversion to OspA. Spirochetes grown at 30, 34, or 38 degrees C had the same median infectious dose. Growth temperature did not influence infectious dose when mice were i noculated intraperitoneally or intradermally and did not influence dos e-related immunologic recognition of OspA. Mice hyperimmunized with re combinant OspA-glutathione S-transferase (GT) fusion protein or GT (co ntrols) were challenged by syringe inoculation with 10(3) spirochetes or by transplantation of infected skin from syngeneic mice infected fo r 2 or 8 weeks. OspA-GT-immunized mice resisted syringe challenge but developed disseminated infections following transplantation of infecte d skin. Identical results were obtained in mice passively immunized wi th hyperimmune serum to OspA-GT or GT and then challenged by syringe o r infected skin transplant. The number of spirochetes in infected skin , determined by quantitative PCR directed toward both plasmid and geno mic targets, was less than-the syringe challenge dose.