New Epitopes for the Serodiagnosis of Human Borreliosis

Lyme disease, a zoonotic infection caused by the bacterium <i>Borrelia burgdorferi</i>, is transmitted to humans through the bites of infected ticks. Its diagnosis primarily relies on serological methods; however, the existing borreliosis techniques have shown a variable sensitivity and...

Full description

Saved in:
Bibliographic Details
Main Authors: Mônica E. T. Alcón-Chino, Virgínia L. N. Bonoldi, Rosa M. R. Pereira, Gilberto S. Gazeta, João P. R. S. Carvalho, Paloma Napoleão-Pêgo, Andressa M. Durans, André L. A. Souza, Salvatore G. De-Simone
Format: Article
Language:English
Published: MDPI AG 2024-10-01
Series:Microorganisms
Subjects:
Online Access:https://www.mdpi.com/2076-2607/12/11/2212
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1846152849852989440
author Mônica E. T. Alcón-Chino
Virgínia L. N. Bonoldi
Rosa M. R. Pereira
Gilberto S. Gazeta
João P. R. S. Carvalho
Paloma Napoleão-Pêgo
Andressa M. Durans
André L. A. Souza
Salvatore G. De-Simone
author_facet Mônica E. T. Alcón-Chino
Virgínia L. N. Bonoldi
Rosa M. R. Pereira
Gilberto S. Gazeta
João P. R. S. Carvalho
Paloma Napoleão-Pêgo
Andressa M. Durans
André L. A. Souza
Salvatore G. De-Simone
author_sort Mônica E. T. Alcón-Chino
collection DOAJ
description Lyme disease, a zoonotic infection caused by the bacterium <i>Borrelia burgdorferi</i>, is transmitted to humans through the bites of infected ticks. Its diagnosis primarily relies on serological methods; however, the existing borreliosis techniques have shown a variable sensitivity and specificity. Our study aimed to map IgG epitopes from five outer membrane proteins (Omp) from <i>B. burgdorferi</i> [Filament flagellar 41kD (PI1089), flagellar hook-associated protein (Q44767), Flagellar hook k2 protein (O51173), Putative Omp BURGA03 (Q44849), and 31 kDa OspA (P0CL66)] lipoprotein to find specific epitopes for the development of accurate diagnosis methods. Using the spot synthesis technique, a library of 380 peptides was constructed to identify linear B cell epitopes recognized by human IgG in response to specific <i>B. burgdorferi</i>-associated proteins. The reactivity of this epitope when chemically synthesized was then evaluated using ELISA with a panel of the patient’s sera. Cross-reactivity was assessed through data bank access and in vitro analysis. Among the 19 epitopes identified, four were selected for further investigation based on their signal intensity, secondary structure, and peptide matching. Validation was performed using ELISA, and ROC curve analysis demonstrated a sensitivity of ≥85.71%, specificity of ≥92.31, accuracy of ≥90.7, and AUC value of ≥0.91 for all peptides. Our cross-reactivity analysis demonstrated that the Burg/02/huG, Burg/03/huG, and Burg/12/huG peptides were not reactive to antibodies from patients with Leptospirosis and syphilis compared to those from the <i>B. burgdorferi</i> group. These peptides indicated an excellent performance in distinguishing between <i>B. burgdorferi</i>-infected and non-infected individuals and exhibited a neglected reactivity to antibodies in sera from patients with Leptospirosis and syphilis. These peptides are promising targets for recombinant development, potentially leading to more accurate serological tests and vaccines.
format Article
id doaj-art-5a01065317fd4e1d81456b5c9d3e0090
institution Kabale University
issn 2076-2607
language English
publishDate 2024-10-01
publisher MDPI AG
record_format Article
series Microorganisms
spelling doaj-art-5a01065317fd4e1d81456b5c9d3e00902024-11-26T18:14:32ZengMDPI AGMicroorganisms2076-26072024-10-011211221210.3390/microorganisms12112212New Epitopes for the Serodiagnosis of Human BorreliosisMônica E. T. Alcón-Chino0Virgínia L. N. Bonoldi1Rosa M. R. Pereira2Gilberto S. Gazeta3João P. R. S. Carvalho4Paloma Napoleão-Pêgo5Andressa M. Durans6André L. A. Souza7Salvatore G. De-Simone8Center for Technological Development in Health (CDTS), National Institute of Science and Technology for Innovation in Neglected Population Diseases (INCT-IDPN), FIOCRUZ, Rio de Janeiro 21040-900, RJ, BrazilClinical Hospital, Faculty of Medicine, São Paulo University, São Paulo 05403-000, SP, BrazilFaculty of Medicine, São Paulo University, São Paulo 01246-903, SP, BrazilLaboratory of Ticks and Other Wingless Arthropods-National Reference for Vectors of Rickettsioses, Instituto Oswaldo Cruz-IOC, FIOCRUZ, Rio de Janeiro 21041-250, RJ, BrazilCenter for Technological Development in Health (CDTS), National Institute of Science and Technology for Innovation in Neglected Population Diseases (INCT-IDPN), FIOCRUZ, Rio de Janeiro 21040-900, RJ, BrazilCenter for Technological Development in Health (CDTS), National Institute of Science and Technology for Innovation in Neglected Population Diseases (INCT-IDPN), FIOCRUZ, Rio de Janeiro 21040-900, RJ, BrazilCenter for Technological Development in Health (CDTS), National Institute of Science and Technology for Innovation in Neglected Population Diseases (INCT-IDPN), FIOCRUZ, Rio de Janeiro 21040-900, RJ, BrazilMultidisciplinary Biochemistry Teaching Laboratory, UNIG, Nova Iguaçu 26260-045, RJ, BrazilCenter for Technological Development in Health (CDTS), National Institute of Science and Technology for Innovation in Neglected Population Diseases (INCT-IDPN), FIOCRUZ, Rio de Janeiro 21040-900, RJ, BrazilLyme disease, a zoonotic infection caused by the bacterium <i>Borrelia burgdorferi</i>, is transmitted to humans through the bites of infected ticks. Its diagnosis primarily relies on serological methods; however, the existing borreliosis techniques have shown a variable sensitivity and specificity. Our study aimed to map IgG epitopes from five outer membrane proteins (Omp) from <i>B. burgdorferi</i> [Filament flagellar 41kD (PI1089), flagellar hook-associated protein (Q44767), Flagellar hook k2 protein (O51173), Putative Omp BURGA03 (Q44849), and 31 kDa OspA (P0CL66)] lipoprotein to find specific epitopes for the development of accurate diagnosis methods. Using the spot synthesis technique, a library of 380 peptides was constructed to identify linear B cell epitopes recognized by human IgG in response to specific <i>B. burgdorferi</i>-associated proteins. The reactivity of this epitope when chemically synthesized was then evaluated using ELISA with a panel of the patient’s sera. Cross-reactivity was assessed through data bank access and in vitro analysis. Among the 19 epitopes identified, four were selected for further investigation based on their signal intensity, secondary structure, and peptide matching. Validation was performed using ELISA, and ROC curve analysis demonstrated a sensitivity of ≥85.71%, specificity of ≥92.31, accuracy of ≥90.7, and AUC value of ≥0.91 for all peptides. Our cross-reactivity analysis demonstrated that the Burg/02/huG, Burg/03/huG, and Burg/12/huG peptides were not reactive to antibodies from patients with Leptospirosis and syphilis compared to those from the <i>B. burgdorferi</i> group. These peptides indicated an excellent performance in distinguishing between <i>B. burgdorferi</i>-infected and non-infected individuals and exhibited a neglected reactivity to antibodies in sera from patients with Leptospirosis and syphilis. These peptides are promising targets for recombinant development, potentially leading to more accurate serological tests and vaccines.https://www.mdpi.com/2076-2607/12/11/2212epitope mappingBrazilian borreliosisELISAcross-reactivity
spellingShingle Mônica E. T. Alcón-Chino
Virgínia L. N. Bonoldi
Rosa M. R. Pereira
Gilberto S. Gazeta
João P. R. S. Carvalho
Paloma Napoleão-Pêgo
Andressa M. Durans
André L. A. Souza
Salvatore G. De-Simone
New Epitopes for the Serodiagnosis of Human Borreliosis
Microorganisms
epitope mapping
Brazilian borreliosis
ELISA
cross-reactivity
title New Epitopes for the Serodiagnosis of Human Borreliosis
title_full New Epitopes for the Serodiagnosis of Human Borreliosis
title_fullStr New Epitopes for the Serodiagnosis of Human Borreliosis
title_full_unstemmed New Epitopes for the Serodiagnosis of Human Borreliosis
title_short New Epitopes for the Serodiagnosis of Human Borreliosis
title_sort new epitopes for the serodiagnosis of human borreliosis
topic epitope mapping
Brazilian borreliosis
ELISA
cross-reactivity
url https://www.mdpi.com/2076-2607/12/11/2212
work_keys_str_mv AT monicaetalconchino newepitopesfortheserodiagnosisofhumanborreliosis
AT virginialnbonoldi newepitopesfortheserodiagnosisofhumanborreliosis
AT rosamrpereira newepitopesfortheserodiagnosisofhumanborreliosis
AT gilbertosgazeta newepitopesfortheserodiagnosisofhumanborreliosis
AT joaoprscarvalho newepitopesfortheserodiagnosisofhumanborreliosis
AT palomanapoleaopego newepitopesfortheserodiagnosisofhumanborreliosis
AT andressamdurans newepitopesfortheserodiagnosisofhumanborreliosis
AT andrelasouza newepitopesfortheserodiagnosisofhumanborreliosis
AT salvatoregdesimone newepitopesfortheserodiagnosisofhumanborreliosis