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J Immunol. 2016 Feb 1;196(3):1036-43. doi: 10.4049/jimmunol.1501861. Epub 2015 Dec 30.

Epitope-Specific Evolution of Human B Cell Responses to Borrelia burgdorferi VlsE Protein from Early to Late Stages of Lyme Disease.

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Department of Medicine, Columbia University Medical Center, New York, NY 10032;
Institute for Experimental Immunology, Euroimmun AG, D-23560 Lubeck, Germany;
University of Kentucky College of Medicine, Lexington, KY 40536;
Division of Infectious Diseases, Department of Medicine, New York Medical College, Valhalla, NY 10595; and.
Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20814.
Department of Medicine, Columbia University Medical Center, New York, NY 10032;


Most immunogenic proteins of Borrelia burgdorferi, the causative agent of Lyme disease, are known or expected to contain multiple B cell epitopes. However, the kinetics of the development of human B cell responses toward the various epitopes of individual proteins during the course of Lyme disease has not been examined. Using the highly immunogenic VlsE as a model Ag, we investigated the evolution of humoral immune responses toward its immunodominant sequences in 90 patients with a range of early to late manifestations of Lyme disease. The results demonstrate the existence of asynchronous, independently developing, Ab responses against the two major immunogenic regions of the VlsE molecule in the human host. Despite their strong immunogenicity, the target epitopes were inaccessible to Abs on intact spirochetes, suggesting a lack of direct immunoprotective effect. These observations document the association of immune reactivity toward specific VlsE sequences with different phases of Lyme disease, demonstrating the potential use of detailed epitope mapping of Ags for staging of the infection, and offer insights regarding the pathogen's possible immune evasion mechanisms.

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