title: Circumvention of outer surface protein A immunity by host-adapted Borrelia burgdorferi.
abstract: Outer surface protein A (OspA), which is abundantly expressed in cultured Borrelia burgdorferi, appears to be down-regulated or masked following low-dose infection, and OspA immunization did not prevent infection, dissemination, or disease development with host-adapted spirochetes. 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 not 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 inoculated intraperitoneally or intradermally and did not influence dose-related immunologic recognition of OspA. Mice hyperimmunized with recombinant OspA-glutathione S-transferase (GT) fusion protein or GT (controls) were challenged by syringe inoculation with 10(3) spirochetes or by transplantation of infected skin from syngenic mice infected for 2 or 8 weeks. OspA-GT-immunized mice resisted syringe challenge but developed disseminated infections following transplantation of infected skin. Identical results were obtained in mice passively immunized with hyperimmune serum to OspA-GT or GT and then challenged by syringe or infected skin transplant. The number of spirochetes in infected skin, determined by quantitative PCR directed toward both plasmid and genomic targets, was less than the syringe challenge dose.
authors.affiliation: Section of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
authors.forename: S W
authors.initials: SW
authors.lastname: Barthold
authors.forename: E
authors.initials: E
authors.lastname: Fikrig
authors.forename: L K
authors.initials: LK
authors.lastname: Bockenstedt
authors.forename: D H
authors.initials: DH
authors.lastname: Persing
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D000954:Antigens, Surface / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D001428:Bacterial Vaccines; D015748:Borrelia burgdorferi Group / Q000276:immunology*; D005982:Glutathione Transferase / Q000276:immunology; D007114:Immunization; D008074:Lipoproteins; D051379:Mice; D008809:Mice, Inbred C3H; D013696:Temperature
chemical_list: D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D008074:Lipoproteins; C072045:OspA protein; D005982:Glutathione Transferase