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Multi-epitope vaccine candidates based on mycobacterial membrane protein large (MmpL) proteins against Mycobacterium ulcerans

Buruli ulcer (BU) is a neglected tropical disease. It is caused by the bacterium Mycobacterium ulcerans and is characterized by skin lesions. Several studies were performed testing the Bacillus Calmette-Guérin (BCG) vaccine in human and animal models and M. ulcerans-specific vaccines in animal model...

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Autores principales: Ishwarlall, Tamara Z., Adeleke, Victoria T., Maharaj, Leah, Okpeku, Moses, Adeniyi, Adebayo A., Adeleke, Matthew A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10645115/
https://www.ncbi.nlm.nih.gov/pubmed/37935359
http://dx.doi.org/10.1098/rsob.230330
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author Ishwarlall, Tamara Z.
Adeleke, Victoria T.
Maharaj, Leah
Okpeku, Moses
Adeniyi, Adebayo A.
Adeleke, Matthew A.
author_facet Ishwarlall, Tamara Z.
Adeleke, Victoria T.
Maharaj, Leah
Okpeku, Moses
Adeniyi, Adebayo A.
Adeleke, Matthew A.
author_sort Ishwarlall, Tamara Z.
collection PubMed
description Buruli ulcer (BU) is a neglected tropical disease. It is caused by the bacterium Mycobacterium ulcerans and is characterized by skin lesions. Several studies were performed testing the Bacillus Calmette-Guérin (BCG) vaccine in human and animal models and M. ulcerans-specific vaccines in animal models. However, there are currently no clinically accepted vaccines to prevent M. ulcerans infection. The aim of this study was to identify T-cell and B-cell epitopes from the mycobacterial membrane protein large (MmpL) proteins of M. ulcerans. These epitopes were analysed for properties including antigenicity, immunogenicity, non-allergenicity, non-toxicity, population coverage and the potential to induce cytokines. The final 8 CD8(+), 12 CD4(+) T-cell and 5 B-cell epitopes were antigenic, non-allergenic and non-toxic. The estimated global population coverage of the CD8(+) and CD4(+) epitopes was 97.71%. These epitopes were used to construct five multi-epitope vaccine constructs with different adjuvants and linker combinations. The constructs underwent further structural analyses and refinement. The constructs were then docked with Toll-like receptors. Three of the successfully docked complexes were structurally analysed. Two of the docked complexes successfully underwent molecular dynamics simulations (MDS) and post-MDS analysis. The complexes generated were found to be stable. However, experimental validation of the complexes is required.
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spelling pubmed-106451152023-11-08 Multi-epitope vaccine candidates based on mycobacterial membrane protein large (MmpL) proteins against Mycobacterium ulcerans Ishwarlall, Tamara Z. Adeleke, Victoria T. Maharaj, Leah Okpeku, Moses Adeniyi, Adebayo A. Adeleke, Matthew A. Open Biol Research Buruli ulcer (BU) is a neglected tropical disease. It is caused by the bacterium Mycobacterium ulcerans and is characterized by skin lesions. Several studies were performed testing the Bacillus Calmette-Guérin (BCG) vaccine in human and animal models and M. ulcerans-specific vaccines in animal models. However, there are currently no clinically accepted vaccines to prevent M. ulcerans infection. The aim of this study was to identify T-cell and B-cell epitopes from the mycobacterial membrane protein large (MmpL) proteins of M. ulcerans. These epitopes were analysed for properties including antigenicity, immunogenicity, non-allergenicity, non-toxicity, population coverage and the potential to induce cytokines. The final 8 CD8(+), 12 CD4(+) T-cell and 5 B-cell epitopes were antigenic, non-allergenic and non-toxic. The estimated global population coverage of the CD8(+) and CD4(+) epitopes was 97.71%. These epitopes were used to construct five multi-epitope vaccine constructs with different adjuvants and linker combinations. The constructs underwent further structural analyses and refinement. The constructs were then docked with Toll-like receptors. Three of the successfully docked complexes were structurally analysed. Two of the docked complexes successfully underwent molecular dynamics simulations (MDS) and post-MDS analysis. The complexes generated were found to be stable. However, experimental validation of the complexes is required. The Royal Society 2023-11-08 /pmc/articles/PMC10645115/ /pubmed/37935359 http://dx.doi.org/10.1098/rsob.230330 Text en © 2023 The Authors. https://creativecommons.org/licenses/by/4.0/Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, provided the original author and source are credited.
spellingShingle Research
Ishwarlall, Tamara Z.
Adeleke, Victoria T.
Maharaj, Leah
Okpeku, Moses
Adeniyi, Adebayo A.
Adeleke, Matthew A.
Multi-epitope vaccine candidates based on mycobacterial membrane protein large (MmpL) proteins against Mycobacterium ulcerans
title Multi-epitope vaccine candidates based on mycobacterial membrane protein large (MmpL) proteins against Mycobacterium ulcerans
title_full Multi-epitope vaccine candidates based on mycobacterial membrane protein large (MmpL) proteins against Mycobacterium ulcerans
title_fullStr Multi-epitope vaccine candidates based on mycobacterial membrane protein large (MmpL) proteins against Mycobacterium ulcerans
title_full_unstemmed Multi-epitope vaccine candidates based on mycobacterial membrane protein large (MmpL) proteins against Mycobacterium ulcerans
title_short Multi-epitope vaccine candidates based on mycobacterial membrane protein large (MmpL) proteins against Mycobacterium ulcerans
title_sort multi-epitope vaccine candidates based on mycobacterial membrane protein large (mmpl) proteins against mycobacterium ulcerans
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10645115/
https://www.ncbi.nlm.nih.gov/pubmed/37935359
http://dx.doi.org/10.1098/rsob.230330
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