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Construction and validation of a multi-epitope in silico vaccine model for lymphatic filariasis by targeting Brugia malayi: a reverse vaccinology approach

BACKGROUND: Lymphatic filariasis (LF), often referred to as elephantiasis, has been identified as one of the 17 neglected tropical diseases by the World Health Organization. Currently, there are no vaccines available to treat this infection in humans. Therefore, with the objective of devising a nove...

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Autores principales: Madanagopal, Premnath, Muthusamy, Sathya, Pradhan, Satya Narayan, Prince, Prabhu Rajaiah
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10037386/
https://www.ncbi.nlm.nih.gov/pubmed/36987521
http://dx.doi.org/10.1186/s42269-023-01013-0
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author Madanagopal, Premnath
Muthusamy, Sathya
Pradhan, Satya Narayan
Prince, Prabhu Rajaiah
author_facet Madanagopal, Premnath
Muthusamy, Sathya
Pradhan, Satya Narayan
Prince, Prabhu Rajaiah
author_sort Madanagopal, Premnath
collection PubMed
description BACKGROUND: Lymphatic filariasis (LF), often referred to as elephantiasis, has been identified as one of the 17 neglected tropical diseases by the World Health Organization. Currently, there are no vaccines available to treat this infection in humans. Therefore, with the objective of devising a novel preventive measure, we exploited an immunoinformatics approach to design a multi-epitope-based subunit vaccine for LF, that can elicit a variety of immune responses within the host. In this study, different B cell, T(C) cell, and T(H) cell-binding epitopes were screened from the antigenic proteins of Brugia malayi and they were passed through several immunological filters to determine the optimal epitopes. RESULTS: As a result, 15 CD8+, 3 CD4+, and 3 B cell epitopes were found to be prominent, antigenic, non-toxic, immunogenic and non-allergenic. The presence of conformational B cell epitopes and cytokine-inducing epitopes confirmed the humoral and cell-mediated immune response that would be triggered by the constructed vaccine model. Following that, the selected epitopes and TLR-4-specific adjuvant were ligated by appropriate peptide linkers to finalize the vaccine construct. Protein–protein docking of the vaccine structure with the TLR4 receptor predicted strong binding affinity and hence putatively confirms its ability to elicit an immune response. Further, the efficiency of the vaccine candidate to provide a long-lasting protective immunity was assessed by in silico immune simulation. The reverse translated vaccine sequence was also virtually cloned in the pET28a (+) plasmid after the optimization of the gene sequence. CONCLUSION: So taken together, by monitoring the overall in silico assessment, we hypothesize that our engineered peptide vaccine could be a viable prophylactic approach in the development of vaccines against the threat of human lymphatic filariasis. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s42269-023-01013-0.
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spelling pubmed-100373862023-03-24 Construction and validation of a multi-epitope in silico vaccine model for lymphatic filariasis by targeting Brugia malayi: a reverse vaccinology approach Madanagopal, Premnath Muthusamy, Sathya Pradhan, Satya Narayan Prince, Prabhu Rajaiah Bull Natl Res Cent Research BACKGROUND: Lymphatic filariasis (LF), often referred to as elephantiasis, has been identified as one of the 17 neglected tropical diseases by the World Health Organization. Currently, there are no vaccines available to treat this infection in humans. Therefore, with the objective of devising a novel preventive measure, we exploited an immunoinformatics approach to design a multi-epitope-based subunit vaccine for LF, that can elicit a variety of immune responses within the host. In this study, different B cell, T(C) cell, and T(H) cell-binding epitopes were screened from the antigenic proteins of Brugia malayi and they were passed through several immunological filters to determine the optimal epitopes. RESULTS: As a result, 15 CD8+, 3 CD4+, and 3 B cell epitopes were found to be prominent, antigenic, non-toxic, immunogenic and non-allergenic. The presence of conformational B cell epitopes and cytokine-inducing epitopes confirmed the humoral and cell-mediated immune response that would be triggered by the constructed vaccine model. Following that, the selected epitopes and TLR-4-specific adjuvant were ligated by appropriate peptide linkers to finalize the vaccine construct. Protein–protein docking of the vaccine structure with the TLR4 receptor predicted strong binding affinity and hence putatively confirms its ability to elicit an immune response. Further, the efficiency of the vaccine candidate to provide a long-lasting protective immunity was assessed by in silico immune simulation. The reverse translated vaccine sequence was also virtually cloned in the pET28a (+) plasmid after the optimization of the gene sequence. CONCLUSION: So taken together, by monitoring the overall in silico assessment, we hypothesize that our engineered peptide vaccine could be a viable prophylactic approach in the development of vaccines against the threat of human lymphatic filariasis. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s42269-023-01013-0. Springer Berlin Heidelberg 2023-03-24 2023 /pmc/articles/PMC10037386/ /pubmed/36987521 http://dx.doi.org/10.1186/s42269-023-01013-0 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research
Madanagopal, Premnath
Muthusamy, Sathya
Pradhan, Satya Narayan
Prince, Prabhu Rajaiah
Construction and validation of a multi-epitope in silico vaccine model for lymphatic filariasis by targeting Brugia malayi: a reverse vaccinology approach
title Construction and validation of a multi-epitope in silico vaccine model for lymphatic filariasis by targeting Brugia malayi: a reverse vaccinology approach
title_full Construction and validation of a multi-epitope in silico vaccine model for lymphatic filariasis by targeting Brugia malayi: a reverse vaccinology approach
title_fullStr Construction and validation of a multi-epitope in silico vaccine model for lymphatic filariasis by targeting Brugia malayi: a reverse vaccinology approach
title_full_unstemmed Construction and validation of a multi-epitope in silico vaccine model for lymphatic filariasis by targeting Brugia malayi: a reverse vaccinology approach
title_short Construction and validation of a multi-epitope in silico vaccine model for lymphatic filariasis by targeting Brugia malayi: a reverse vaccinology approach
title_sort construction and validation of a multi-epitope in silico vaccine model for lymphatic filariasis by targeting brugia malayi: a reverse vaccinology approach
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10037386/
https://www.ncbi.nlm.nih.gov/pubmed/36987521
http://dx.doi.org/10.1186/s42269-023-01013-0
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