title: Borrelia burgdorferi antigens that are targeted by antibody-dependent, complement-mediated killing in the rhesus monkey.
abstract: We identified surface antigens of Borrelia burgdorferi that are targeted by antibody-dependent, complement-mediated killing (ADCK) in the rhesus monkey. For this purpose, we had available serum samples from three animals infected with B. burgdorferi JD1 by needle inoculation and from two monkeys that were infected with the same B. burgdorferi strain by Ixodes scapularis tick bite. Sera from monkeys from the first group contained antibodies to OspA and OspB detectable by Western blot (immunoblot) using whole B. burgdorferi antigens, whereas serum samples from animals in the second group did not. The targeting of OspA and OspB by functional antibodies was demonstrated directly by showing that ADCK was partially inhibited when antibodies were preincubated with an excess of soluble recombinant OspA or OspB. Simultaneous addition of OspA and OspB did not result in an additive inhibitory effect on ADCK, a result that suggests that the epitopes on OspA and that on OspB targeted by antibody in this mechanism are the same, or at least cross-reacting. The targeting of non-OspA, non-OspB surface antigens was inferred from the fact that sera from tick-inoculated animals, which did not contain detectable anti-OspA or anti-OspB antibodies, were able to effect ADCK. This killing effect was not inhibitable by the addition of recombinant OspA or OspB or both proteins together. We also showed that both immunoglobulin G and M antibodies participate in the ADCK mechanism in the rhesus monkey. Rhesus complement does not kill B. burgdorferi in vitro in the absence of antibody, and antibody alone is effective in killing only at serum dilutions lower than 1:15. However, such "complement-independent" antibodies were not present in all bleeds. Two main conclusions may be drawn from the analysis of our results. First, both OspA and OspB are targeted by the ADCK mechanism in the rhesus monkey. Second, one or more B. burgdorferi surface antigens that are neither OspA nor OspB also participate in ADCK.
authors.affiliation: Department of Parasitology, Tulane Regional Primate Research Center, Tulane University Medical Center, Covington, Louisiana 70433.
authors.forename: M K
authors.initials: MK
authors.lastname: Aydintug
authors.forename: Y
authors.initials: Y
authors.lastname: Gu
authors.forename: M T
authors.initials: MT
authors.lastname: Philipp
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D000918:Antibody Specificity; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D001428:Bacterial Vaccines; D001770:Blood Bactericidal Activity; D015748:Borrelia burgdorferi Group / Q000276:immunology*; D003167:Complement Activation; D003602:Cytotoxicity, Immunologic; D007132:Immunoglobulin Isotypes / Q000276:immunology; D008074:Lipoproteins; D008193:Lyme Disease / Q000276:immunology*; D008253:Macaca mulatta; D008297:Male; D013987:Ticks
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D007132:Immunoglobulin Isotypes; D008074:Lipoproteins; C072045:OspA protein; C077030:OspB protein, Borrelia burgdorferi