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Immunoinformatic-based design of immune-boosting multiepitope subunit vaccines against monkeypox virus and validation through molecular dynamics and immune simulation

Monkeypox virus is the causative agent of monkeypox disease, belonging to an orthopoxvirus genus, with a disease pattern similar to that of smallpox. The number of monkeypox cases have robustly increased recently in several countries around the world, potentially causing an international threat. The...

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Autores principales: Suleman, Muhammad, Rashid, Farooq, Ali, Shahid, Sher, Hassan, Luo, Sisi, Xie, Liji, Xie, Zhixun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9606240/
https://www.ncbi.nlm.nih.gov/pubmed/36311718
http://dx.doi.org/10.3389/fimmu.2022.1042997
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author Suleman, Muhammad
Rashid, Farooq
Ali, Shahid
Sher, Hassan
Luo, Sisi
Xie, Liji
Xie, Zhixun
author_facet Suleman, Muhammad
Rashid, Farooq
Ali, Shahid
Sher, Hassan
Luo, Sisi
Xie, Liji
Xie, Zhixun
author_sort Suleman, Muhammad
collection PubMed
description Monkeypox virus is the causative agent of monkeypox disease, belonging to an orthopoxvirus genus, with a disease pattern similar to that of smallpox. The number of monkeypox cases have robustly increased recently in several countries around the world, potentially causing an international threat. Therefore, serious measures are indispensable to be taken to mitigate the spread of the disease and hence, under these circumstances, vaccination is the best choice to neutralize the monkeypox virus. In the current study, we used immunoinformatic approaches to target the L1R, B5R, and A33R proteins of the monkeypox virus to screen for immunogenic cytotoxic T-lymphocyte (CTL), helper T-lymphocyte (HTL), and B-cell epitopes to construct multiepitope subunit vaccines. Various online tools predicted the best epitope from immunogenic targets (L1R, B5R, and A33R) of monkeypox virus. The predicted epitopes were joined together by different linkers and subjected to 3D structure prediction. Molecular dynamics simulation analysis confirmed the proper folding of the modeled proteins. The strong binding of the constructed vaccines with human TLR-2 was verified by the molecular docking and determination of dissociation constant values. The GC content and codon adaptation index (CAI) values confirmed the high expression of the constructed vaccines in the pET-28a (+) expression vector. The immune response simulation data delineated that the injected vaccines robustly activated the immune system, triggering the production of high titers of IgG and IgM antibodies. In conclusion, this study provided a solid base of concept to develop dynamic and effective vaccines that contain several monkeypox virus-derived highly antigenic and nonallergenic peptides to control the current pandemic of monkeypox virus.
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spelling pubmed-96062402022-10-28 Immunoinformatic-based design of immune-boosting multiepitope subunit vaccines against monkeypox virus and validation through molecular dynamics and immune simulation Suleman, Muhammad Rashid, Farooq Ali, Shahid Sher, Hassan Luo, Sisi Xie, Liji Xie, Zhixun Front Immunol Immunology Monkeypox virus is the causative agent of monkeypox disease, belonging to an orthopoxvirus genus, with a disease pattern similar to that of smallpox. The number of monkeypox cases have robustly increased recently in several countries around the world, potentially causing an international threat. Therefore, serious measures are indispensable to be taken to mitigate the spread of the disease and hence, under these circumstances, vaccination is the best choice to neutralize the monkeypox virus. In the current study, we used immunoinformatic approaches to target the L1R, B5R, and A33R proteins of the monkeypox virus to screen for immunogenic cytotoxic T-lymphocyte (CTL), helper T-lymphocyte (HTL), and B-cell epitopes to construct multiepitope subunit vaccines. Various online tools predicted the best epitope from immunogenic targets (L1R, B5R, and A33R) of monkeypox virus. The predicted epitopes were joined together by different linkers and subjected to 3D structure prediction. Molecular dynamics simulation analysis confirmed the proper folding of the modeled proteins. The strong binding of the constructed vaccines with human TLR-2 was verified by the molecular docking and determination of dissociation constant values. The GC content and codon adaptation index (CAI) values confirmed the high expression of the constructed vaccines in the pET-28a (+) expression vector. The immune response simulation data delineated that the injected vaccines robustly activated the immune system, triggering the production of high titers of IgG and IgM antibodies. In conclusion, this study provided a solid base of concept to develop dynamic and effective vaccines that contain several monkeypox virus-derived highly antigenic and nonallergenic peptides to control the current pandemic of monkeypox virus. Frontiers Media S.A. 2022-10-13 /pmc/articles/PMC9606240/ /pubmed/36311718 http://dx.doi.org/10.3389/fimmu.2022.1042997 Text en Copyright © 2022 Suleman, Rashid, Ali, Sher, Luo, Xie and Xie https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Suleman, Muhammad
Rashid, Farooq
Ali, Shahid
Sher, Hassan
Luo, Sisi
Xie, Liji
Xie, Zhixun
Immunoinformatic-based design of immune-boosting multiepitope subunit vaccines against monkeypox virus and validation through molecular dynamics and immune simulation
title Immunoinformatic-based design of immune-boosting multiepitope subunit vaccines against monkeypox virus and validation through molecular dynamics and immune simulation
title_full Immunoinformatic-based design of immune-boosting multiepitope subunit vaccines against monkeypox virus and validation through molecular dynamics and immune simulation
title_fullStr Immunoinformatic-based design of immune-boosting multiepitope subunit vaccines against monkeypox virus and validation through molecular dynamics and immune simulation
title_full_unstemmed Immunoinformatic-based design of immune-boosting multiepitope subunit vaccines against monkeypox virus and validation through molecular dynamics and immune simulation
title_short Immunoinformatic-based design of immune-boosting multiepitope subunit vaccines against monkeypox virus and validation through molecular dynamics and immune simulation
title_sort immunoinformatic-based design of immune-boosting multiepitope subunit vaccines against monkeypox virus and validation through molecular dynamics and immune simulation
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9606240/
https://www.ncbi.nlm.nih.gov/pubmed/36311718
http://dx.doi.org/10.3389/fimmu.2022.1042997
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