title: Enhanced Protective Immunogenicity of Homodimeric Borrelia burgdorferi Outer Surface Protein C.
abstract: Lyme borreliosis is caused by tick-transmitted spirochetes of the Borrelia burgdorferi sensu lato group and is the most common vector-borne disease in the United States and Europe. Outer surface protein C (OspC) is a 23-kDa outer surface lipoprotein expressed during spirochete transmission from the tick to the vertebrate host. In a previous study, we found that immunization with a recombinant disulfide-bridged dimeric form of OspC (D-OspC) stimulates increased antibody responses relative to immunization with commonly employed monomeric OspC. Here, we report that mice immunized with dimeric OspC proteins also exhibited enhanced protection against infection with the cognate B. burgdorferi strain. Mice were protected by four immunizations containing as little as 100 ng of dimeric OspC, suggesting that this form of the protein can induce protective immunity within a dose range reasonable for a human or veterinary vaccine. In contrast, monomeric OspC was only partially protective at much higher doses. IgG subclass analysis revealed that D-OspC-immunized animals mainly possessed anti-OspC-IgG1. In contrast, infected animals develop anti-OspC restricted to the IgG3 isotype. A subset of antibodies generated by dimeric OspC immunization did not recognize the monomeric variant, indicating that unique epitopes exist on the dimeric form. Moreover, monoclonal antibodies that recognized only dimeric OspC protected mice from B. burgdorferi challenge, whereas another monoclonal that recognized both immunogens was not protective. These studies suggest that this dimeric OspC presents distinctive epitopes that generate antibodies protective against B. burgdorferi infection and could be a useful vaccine component.
authors.affiliation: Department of Pathology & Laboratory Medicine, Medical School, University of Texas, Houston, Texas, USA.
authors.forename: Diane G
authors.initials: DG
authors.lastname: Edmondson
authors.affiliation: Department of Pathology & Laboratory Medicine, Medical School, University of Texas, Houston, Texas, USA.
authors.forename: Sabitha
authors.initials: S
authors.lastname: Prabhakaran
authors.affiliation: Department of Pathology & Laboratory Medicine, Medical School, University of Texas, Houston, Texas, USA.
authors.forename: Steven J
authors.identifier: http://orcid.org/0000-0002-2501-8034
authors.initials: SJ
authors.lastname: Norris
authors.affiliation: Centers for Disease Control and Prevention, Division of Vector-Borne Disease, Fort Collins, Colorado, USA.
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Ullmann
authors.affiliation: Centers for Disease Control and Prevention, Division of Vector-Borne Disease, Fort Collins, Colorado, USA.
authors.forename: Joe
authors.initials: J
authors.lastname: Piesman
authors.affiliation: Centers for Disease Control and Prevention, Division of Vector-Borne Disease, Fort Collins, Colorado, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Dolan
authors.affiliation: Institute of Experimental Immunology, Euroimmun AG, Lübeck, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Probst
authors.affiliation: Institute of Experimental Immunology, Euroimmun AG, Lübeck, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Radzimski
authors.affiliation: Institute of Experimental Immunology, Euroimmun AG, Lübeck, Germany.
authors.forename: Winfried
authors.initials: W
authors.lastname: Stöcker
authors.affiliation: Institute of Experimental Immunology, Euroimmun AG, Lübeck, Germany l.komorowski@euroimmun.de.
authors.forename: Lars
authors.initials: L
authors.lastname: Komorowski
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000008:administration & dosage / Q000276:immunology*; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D008193:Lyme Disease / Q000517:prevention & control*; D008809:Mice, Inbred C3H; D055503:Protein Multimerization
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D007074:Immunoglobulin G; C079616:OspC protein
keywords: Borrelia; Borrelia burgdorferi; ELISA; Lyme disease; OspC; immunoblot; vaccine