ABSTRACTLyme borreliosis is caused by tick-transmitted spirochetes of theBorrelia burgdorferi sensu latogroup 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 cognateB. burgdorferistrain. 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 fromB. burgdorferichallenge, whereas another monoclonal that recognized both immunogens was not protective. These studies suggest that this dimeric OspC presents distinctive epitopes that generate antibodies protective againstB. burgdorferiinfection and could be a useful vaccine component.
Phenotypic analysis of outer surface protein C (OspC) of Borrelia burgdorferi sensu lato by monoclonal antibodies: relationship to genospecies and OspA serotype.
