Identification of Surface Epitopes Associated with Protection against Highly Immune-Evasive VlsE-Expressing Lyme Disease Spirochetes

Healthy Communities Research Institute, Department of Biological Sciences
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  3. Identification of Surface Epitopes Associated with Protection against Highly Immune-Evasive VlsE-Expressing Lyme Disease Spirochetes
Author(s)
Abstract
The tick-borne pathogen Borrelia burgdorferi is responsible for approximately 300,000 Lyme disease (LD) cases per year in the United States. Recent increases in the number of LD cases, in addition to the spread of the tick vector and a lack of a vaccine, highlight an urgent need for designing and developing an efficacious LD vaccine. Identification of protective epitopes that could be used to develop a second-generation (subunit) vaccine is therefore imperative. Despite the antigenicity of several lipoproteins and integral outer membrane proteins (OMPs) on the B. burgdorferi surface, the spirochetes successfully evade antibodies primarily due to the VlsE-mediated antigenic variation. VlsE is thought to sterically block antibody access to protective epitopes of B. burgdorferi. However, it is highly unlikely that VlsE shields the entire surface epitome. Thus, identification of subdominant epitope targets that induce protection when they are made dominant is necessary to generate an efficacious vaccine. Toward the identification, we repeatedly immunized immunocompetent mice with live-attenuated VlsE-deleted B. burgdorferi and then challenged the animals with the VlsE-expressing (host-adapted) wild type. Passive immunization and Western blotting data suggested that the protection of 50% of repeatedly immunized animals against the highly immune-evasive B. burgdorferi was antibody mediated. Comparison of serum antibody repertoires identified in protected and nonprotected animals permitted the identification of several putative epitopes significantly associated with the protection. Most linear putative epitopes were conserved between the main pathogenic Borrelia genospecies and found within known subdominant regions of OMPs. Currently, we are performing immunization studies to test whether the identified protection-associated epitopes are protective for mice.
Format
Article
Identifier(s)
10.1128/IAI.00182-18
Publication Date
2018-08
Publication Title
Infection and Immunity
Volume
86
Issue
8
Keywords
Subject
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http://rightsstatements.org/vocab/InC/1.0/
Community
Healthy Communities Research Institute
Department of Biological Sciences
Permalink https://oaks.kent.edu/hcri/identification-surface-epitopes-associated-protection-against-highly-immune-evasive-vlse
Batool, M., Caoili, S., Dangott, L., Gerasimov, E., Ionov, Y., Piontkivska, H., Zelikovsky, A., Waghela, S., & Rogovskyy, A. (2018). Identification of Surface Epitopes Associated with Protection against Highly Immune-Evasive VlsE-Expressing Lyme Disease Spirochetes (1–). Infection and Immunity. https://doi.org/http://dx.doi.org/10.1128/IAI.00182-18
Batool, Maliha, Salvador Caoili, Lawrence Dangott, Ekaterina Gerasimov, Yurij Ionov, Helen Piontkivska, Alex Zelikovsky, Suryakant Waghela, and Artem Rogovskyy. 2018. “Identification of Surface Epitopes Associated With Protection Against Highly Immune-Evasive VlsE-Expressing Lyme Disease Spirochetes”. Infection and Immunity. https://doi.org/http://dx.doi.org/10.1128/IAI.00182-18.
Batool, Maliha, et al. Identification of Surface Epitopes Associated With Protection Against Highly Immune-Evasive VlsE-Expressing Lyme Disease Spirochetes. Infection and Immunity, Aug. 2018, https://doi.org/http://dx.doi.org/10.1128/IAI.00182-18.