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Structural Elucidation of a Protective B Cell Epitope on Outer Surface Protein C (OspC) of the Lyme Disease Spirochete, Borreliella burgdorferi
Rudolph, Michael J. ; Davis, Simon A. ; Haque, H. M. Emranul ; Weis, David D. ; Vance, David J. ; Piazza, Carol Lyn ; Ejemel, Monir ; Cavacini, Lisa ; Wang, Yang ; Mbow, M. Lamine ... show 2 more
Rudolph, Michael J.
Davis, Simon A.
Haque, H. M. Emranul
Weis, David D.
Vance, David J.
Piazza, Carol Lyn
Ejemel, Monir
Cavacini, Lisa
Wang, Yang
Mbow, M. Lamine
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Abstract
Outer surface protein C (OspC) plays a pivotal role in mediating tick-to-host transmission and infectivity of the Lyme disease spirochete, Borreliella burgdorferi. OspC is a helical-rich homodimer that interacts with tick salivary proteins, as well as components of the mammalian immune system. Several decades ago, it was shown that the OspC-specific monoclonal antibody, B5, was able to passively protect mice from experimental tick-transmitted infection by B. burgdorferi strain B31. However, B5’s epitope has never been elucidated, despite widespread interest in OspC as a possible Lyme disease vaccine antigen. Here, we report the crystal structure of B5 antigen-binding fragments (Fabs) in complex with recombinant OspC type A (OspCA). Each OspC monomer within the homodimer was bound by a single B5 Fab in a side-on orientation, with contact points along OspC’s α-helix 1 and α-helix 6, as well as interactions with the loop between α-helices 5 and 6. In addition, B5’s complementarity-determining region (CDR) H3 bridged the OspC-OspC′ homodimer interface, revealing the quaternary nature of the protective epitope. To provide insight into the molecular basis of B5 serotype specificity, we solved the crystal structures of recombinant OspC types B and K and compared them to OspCA. This study represents the first structure of a protective B cell epitope on OspC and will aid in the rational design of OspC-based vaccines and therapeutics for Lyme disease.
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Date
2023-03-28
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American Society for Microbiology
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Keywords
Borreliella burgdorferi, Lyme disease, X-ray crystallography, Monoclonal antibodies, Spirochetes, Vaccines
Citation
Rudolph, M. J., Davis, S. A., Haque, H. M. E., Weis, D. D., Vance, D. J., Piazza, C. L., Ejemel, M., Cavacini, L., Wang, Y., Mbow, M. L., Gilmore, R. D., & Mantis, N. J. (2023). Structural Elucidation of a Protective B Cell Epitope on Outer Surface Protein C (OspC) of the Lyme Disease Spirochete, Borreliella burgdorferi. mBio, 14(2), e0298122. https://doi.org/10.1128/mbio.02981-22