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Essential Components of Borreliella Borrelia burgdorferi In Vitro Transcription Assays
Published on: July 22, 2022
Borrelia burgdorferi BBI39 Paralogs, Targets of Protective Immunity, Reduce Pathogen Persistence Either in Hosts or
Preeti Singh1, Deepshikha Verma1, Brian T Backstedt1
1Department of Veterinary Medicine, University of Maryland and Virginia-Maryland, Regional College of Veterinary Medicine, College Park, Maryland, USA.
Abstract:
Borrelia burgdorferi genome harbors several paralogous gene families (pgf) that can encode immunogenic proteins of unknown function. Protein-protein interaction assays using a transmission-blocking vaccine candidate, BBA52, as bait identified an interacting partner in spirochetes-a member of pgf 54, annotated as BBI39. We show that BBI39 is a surface-exposed membrane antigen that is immunogenic during spirochete infection, despite the gene being primarily transcribed in the vector with a transient expression in the host only at tick-bite sites. Immunization of rodents with BBI39, or a diverse paralog, BBI36, or their combination impaired pathogen acquisition by the vector, transmission from ticks to hosts, or induction of disease. High-titer BBI39 immunoglobulin G antibodies, which have borreliacidal properties, could be generated through routine subcutaneous or oral immunization, further highlighting use of BBI39 proteins as novel Lyme disease vaccines that can target pathogens in the host or in ticks.
Insights
Researchers identified BBI39, a surface protein of Borrelia burgdorferi, as a potential target for Lyme disease vaccines. Immunization with BBI39 demonstrated efficacy in preventing pathogen transmission and disease development.
Area of Science:
- Microbiology
- Immunology
- Vaccine Development
Background:
- Borrelia burgdorferi, the causative agent of Lyme disease, possesses numerous paralogous gene families encoding proteins of unknown function.
- Identifying novel antigens is crucial for developing effective Lyme disease vaccines.
Purpose of the Study:
- To identify novel immunogenic proteins from Borrelia burgdorferi.
- To evaluate the potential of BBI39 as a vaccine candidate against Lyme disease.
Main Methods:
- Protein-protein interaction assays using BBA52 as bait to identify interacting partners.
- Characterization of BBI39 as a surface-exposed membrane antigen.
- Immunization studies in rodents using BBI39, BBI36, or a combination.
- Assessment of vaccine efficacy in preventing pathogen acquisition, transmission, and disease induction.
Main Results:
- BBI39 was identified as a binding partner of BBA52 and confirmed as a surface-exposed, immunogenic antigen.
- Immunization with BBI39, BBI36, or their combination significantly impaired Borrelia burgdorferi acquisition by vectors and transmission to hosts.
- High-titer BBI39 immunoglobulin G antibodies with borreliacidal properties were generated via subcutaneous or oral immunization.
Conclusions:
- BBI39 is a promising novel vaccine candidate for Lyme disease, targeting the pathogen in both the host and tick vectors.
- Subcutaneous or oral immunization routes are effective for generating protective antibodies against BBI39.
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