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dc.contributor.authorRudolph, Michael J.
dc.contributor.authorDavis, Simon A.
dc.contributor.authorHaque, H M Emranul
dc.contributor.authorWeis, David D.
dc.contributor.authorVance, David J
dc.contributor.authorPiazza, Carol Lyn
dc.contributor.authorEjemel, Monir
dc.contributor.authorCavacini, Lisa
dc.contributor.authorWang, Yang
dc.contributor.authorMbow, M. Lamine
dc.contributor.authorGilmore, Robert D.
dc.contributor.authorMantis, Nicholas J
dc.date.accessioned2023-01-31T20:52:26Z
dc.date.available2023-01-31T20:52:26Z
dc.date.issued2022-11-29
dc.identifier.citationStructural Elucidation of a Protective B cell Epitope on Outer Surface Protein C (OspC) of the Lyme disease spirochete, Borreliella burgdorferi Michael J. Rudolph, Simon A. Davis, H M Emranul Haque, David D. Weis, David J Vance, Carol Lyn Piazza, Monir Ejemel, Lisa Cavacini, Yang Wang, M. Lamine Mbow, Robert D. Gilmore, Nicholas J Mantis bioRxiv 2022.11.28.518297; doi: https://doi.org/10.1101/2022.11.28.518297en_US
dc.identifier.doi10.1101/2022.11.28.518297en_US
dc.identifier.urihttp://hdl.handle.net/20.500.14038/51615
dc.descriptionThis article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.en_US
dc.description.abstractOuter 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 a-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. IMPORTANCE The spirochete, Borreliella burgdorferi, is the causative agent of Lyme borreliosis, the most common tickborne disease in the United States. The spirochete is transmitted to humans during the course of a tick taking a bloodmeal. After B. burgdorferi is deposited into the skin of a human host, it replicates locally and spreads systemically, often resulting in clinical manifestations involving the central nervous system, joints, and/or heart. Antibodies directed against B. burgdorferi’s outer surface protein C (OspC) are known to block tick-to-host transmission, as well as dissemination of the spirochete within a mammalian host. In this report, we reveal the first atomic structure of one such antibody in complex with OspC. Our results have implications for the design of a Lyme disease vaccine capable to interfering with multiple stages in B. burgdorferi infection.en_US
dc.language.isoen_USen_US
dc.publisherCold Spring Harbor Laboratoryen_US
dc.relation.ispartofbioRxiven_US
dc.relation.urlhttps://doi.org/10.1101/2022.11.28.518297en_US
dc.rightsThe copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.en_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectImmunologyen_US
dc.subjectLyme diseaseen_US
dc.subjectOuter surface protein Cen_US
dc.titleStructural Elucidation of a Protective B cell Epitope on Outer Surface Protein C (OspC) of the Lyme disease spirochete, Borreliella burgdorferi [preprint]en_US
dc.typePreprinten_US
dc.source.journaltitlebioRxiv
refterms.dateFOA2023-01-31T20:52:27Z
dc.contributor.departmentMassBiologicsen_US


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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Except where otherwise noted, this item's license is described as The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.