FtlA and FtlB Are Candidates for Inclusion in a Next-Generation Multiantigen Subunit Vaccine for Lyme Disease.
Abstract: Lyme disease (LD) is a tick-transmitted bacterial infection caused by Borreliella burgdorferi and other closely related species collectively referred to as the LD spirochetes. The LD spirochetes encode an uncharacterized family of proteins originally designated rotein amily welve (PF12). In B. burgdorferi strain B31, PF12 consists of four plasmid-carried genes, encoding BBK01, BBG01, BBH37, and BBJ08. Henceforth, we designate the PF12 proteins amily welve ipoprotein (Ftl) (FtlA) (BBK01), FtlB (BBG01), FtlC (BBH37), and FtlD (BBJ08). The goal of this study was to assess the potential utility of the Ftl proteins in subunit vaccine development. Immunoblot analyses of LD spirochete cell lysates demonstrated that one or more of the Ftl proteins are produced by most LD isolates during cultivation. The Ftl proteins were verified to be membrane associated, and nondenaturing PAGE revealed that FtlA, FtlB, and FtlD formed dimers, while FtlC formed hexamers. Analysis of serum samples from B. burgdorferi antibody (Ab)-positive client-owned dogs ( = 50) and horses ( = 90) revealed that a majority were anti-Ftl Ab positive. Abs to the Ftl proteins were detected in serum samples from laboratory-infected dogs out to 497 days postinfection. Anti-FtlA and FtlB antisera displayed potent complement-dependent Ab-mediated killing activity, and epitope localization revealed that the bactericidal epitopes reside within the N-terminal domain of the Ftl proteins. This study suggests that FtlA and FtlB are potential candidates for inclusion in a multivalent vaccine for LD.
Publication Date: 2022-09-14 PubMed ID: 36102656PubMed Central: PMC9584329DOI: 10.1128/iai.00364-22Google Scholar: Lookup
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Summary
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The research examines the potential of proteins (FtlA and FtlB) in the development of a Lyme disease subunit vaccine. Scientists found that these proteins were present in most Lyme disease strains, confirmed to be membrane-associated, and antibodies against these proteins had strong killing activity.
Introduction
- Lyme disease is an infectious disease transmitted by ticks, mainly caused by the bacterium Borreliella burgdorferi and similar species. This study focuses on a group of proteins produced by these bacteria, known as the PF12 protein family.
- Within a specific strain of B. burgdorferi, four types of these proteins were identified: FtlA, FtlB, FtlC, and FtlD. The researchers aimed to see if these proteins have the potential to be utilized in developing a subunit vaccine for Lyme disease.
Findings
- An analysis of cells from various Lyme disease strains showed that at least one of the Ftl proteins was produced during cultivation. This showed that these proteins are common in Lyme disease bacteria.
- All four proteins were found to be associated with the cell membrane. Further, it was shown that FtlA, FtlB, and FtlD could form dimers (pairs), and FtlC could form hexamers (groups of six).
- Serum analysis from dogs and horses infected with Lyme disease indicated that most had antibodies against Ftl proteins. This provided evidence that these proteins could potentially stimulate an immune response.
Conclusion
- Antibodies against FtlA and FtlB showed potent killing activity against Lyme disease bacteria when combined with complement (part of the immune system). Furthermore, the deadly effect targets the N terminal domain of the Ftl proteins, which might serve as the point of attack for a potential vaccine.
- Bearing in mind these results, FtlA and FtlB proteins emerged as potential good candidates for incorporation into a vaccine against Lyme disease.
Cite This Article
APA
Camire AC, O'Bier NS, Patel DT, Cramer NA, Straubinger RK, Breitschwerdt EB, Funk RA, Marconi RT.
(2022).
FtlA and FtlB Are Candidates for Inclusion in a Next-Generation Multiantigen Subunit Vaccine for Lyme Disease.
Infect Immun, 90(10), e0036422.
https://doi.org/10.1128/iai.00364-22 Publication
Researcher Affiliations
- Department of Microbiology and Immunology, Virginia Commonwealth University Medical Centergrid.417264.2, Richmond, Virginia, USA.
- Department of Microbiology and Immunology, Virginia Commonwealth University Medical Centergrid.417264.2, Richmond, Virginia, USA.
- Department of Microbiology and Immunology, Virginia Commonwealth University Medical Centergrid.417264.2, Richmond, Virginia, USA.
- Department of Microbiology and Immunology, Virginia Commonwealth University Medical Centergrid.417264.2, Richmond, Virginia, USA.
- Institute of Infectious Diseases and Zoonoses, Department of Veterinary Sciences, Faculty of Veterinary Medicine, Ludwig-Maximilians-University, Munich, Germany.
- Department of Clinical Sciences, The Comparative Medicine Institute, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA.
- Department of Large Animal Clinical Sciences, VA-MD College of Veterinary Medicine, Blacksburg, Virginia, USA.
- Department of Microbiology and Immunology, Virginia Commonwealth University Medical Centergrid.417264.2, Richmond, Virginia, USA.
- Department of Oral and Craniofacial Molecular Biology, Philips Institute for Oral Health Research, School of Dentistry, Virginia Commonwealth University, Richmond, Virginia, USA.
MeSH Terms
- Animals
- Dogs
- Antibodies, Bacterial
- Antigens, Bacterial
- Bacterial Outer Membrane Proteins / genetics
- Borrelia burgdorferi
- Epitopes
- Horses
- Immune Sera
- Ixodes / microbiology
- Lipoproteins / genetics
- Lyme Disease / microbiology
- Vaccines, Combined
- Vaccines, Subunit / genetics
Conflict of Interest Statement
The authors declare no conflict of interest.
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