Conformational nature of the Borrelia burgdorferi B31 outer surface protein C protective epitope.
Active immunization with Escherichia coli-expressed recombinant outer surface protein C (OspC) of Borrelia burgdorferi has been demonstrated to confer protection against a tick-transmitted infection on laboratory animals. A previous study in this laboratory showed that OspC antibody raised against a denatured immunogen isolated from B. burgdorferi cells failed to provide protective immunity. Therefore, to determine whether the protective epitope of the recombinant antigen was sensitive to denaturation, recombinant OspC preparations were subjected to heat and chemical treatments prior to animal immunization. Following seroconversion to OspC, the animals were challenged with an infectious dose of B. burgdorferi B31 by tick bite. Whereas mice immunized with a soluble, nondenatured form continued to show protection rates close to 100%, mice that had been immunized with denatured antigen were not protected. Furthermore, mice that were immunized with an insoluble (rather than a soluble), nondenatured form of the recombinant OspC showed a protection rate of only 40%. Protective epitope localization experiments showed that either the amino or the carboxy end of the recombinant protein was required to react with a protective OspC-specific monoclonal antibody. The data from these experiments demonstrate that a conformational organization of the protein is essential for the protective capability of the strain B31 OspC immunogen.
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Division of Vector-Borne Infectious Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Public Health Service, U.S. Department of Health and Human Services, Fort Collins, Colorado 80522, USA. rbg9@cdc.gov
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000276:immunology*; D015748:Borrelia burgdorferi Group / Q000276:immunology*; D000939:Epitopes / Q000737:chemistry*; D051379:Mice; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000276:immunology; D013987:Ticks / Q000382:microbiology
D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D000939:Epitopes; C079616:OspC protein; D011994:Recombinant Proteins