A Refined Human Linear B Cell Epitope Map of Outer Surface Protein C (OspC) From the Lyme Disease Spirochete, Borrelia burgdorferi

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Published: Feb 14, 2025
Keywords:
Lyme disease, antibody, epitope, vaccine, Borrelia burgdorferi, Borreliella, human, peptides

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Grace Freeman-Gallant
Division of Infectious Diseases, Wadsworth Center, New York State Department of Health, Albany, New York
Kathleen McCarthy
Department of Biomedical Sciences, University at Albany, Albany, New York
Jennifer Yates
Division of Infectious Diseases, Wadsworth Center, New York State Department of Health, Albany; Department of Biomedical Sciences, University at Albany, Albany, New York
Karen Kulas
Division of Infectious Diseases, Wadsworth Center, New York State Department of Health, Albany, New York
Michael J. Rudolph
New York Structural Biology Center, New York, New York
David J. Vance
Division of Infectious Diseases, Wadsworth Center, New York State Department of Health, Albany; Department of Biomedical Sciences, University at Albany, Albany, New York
Nicholas J. Mantis
Division of Infectious Diseases, Wadsworth Center, New York State Department of Health, Albany; Department of Biomedical Sciences, University at Albany, Albany, New York
https://orcid.org/0000-0002-5083-8640

Abstract

Background: A detailed understanding of the human antibody response to outer surface protein C (OspC) of Borrelia burgdorferi has important implications for Lyme disease diagnostics and vaccines.


Methods: In this report, 13 peptides encompassing 8 reported OspC linear B-cell epitopes from OspC types A, B, and K, including the largely conserved C-terminus (residues 193-210), were evaluated by multiplex immunoassay (MIA) for IgG reactivity with ~700 human serum samples confirmed positive in a 2-tiered Lyme disease diagnostic assay (Bb+) and ~160 post-treatment Lyme disease (PTLD) serum samples. The vmp-like sequence E (VlsE) C6-17 peptide was included as a positive control.


Results: Serum IgG from Bb+ samples were reactive with 10 of the 13 OspC-derived peptides tested, with the C-terminal peptide (residues 193-210) being the most reactive. Spearman’s rank correlation matrices and hierarchical clustering revealed a strong correlation between 193-210 and VlsE C6-17 peptide reactivity but little demonstrable association between 193-210 and the other OspC peptides or recombinant OspC. OspC peptide reactivities (excluding 193-210) were strongly correlated with each other and were disproportionately influenced by a subset of pan-reactive samples. In the PTLD sample set, none of the OspC-derived peptides were significantly reactive over baseline, even though VlsE C6-17 peptide reactivity remained.


Conclusions: The asynchronous and potentially short-lived serologic response to OspC-derived peptides reveal the complexity of B-cell responses to B. burgdorferi lipoproteins and confounds interpretation of antibody profiles for Lyme disease diagnostics.

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