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Identification of a Potential Vaccine against Treponema pallidum Using Subtractive Proteomics and Reverse-Vaccinology Approaches
Syphilis, a sexually transmitted infection, is a deadly disease caused by Treponema pallidum. It is a Gram-negative spirochete that can infect nearly every organ of the human body. It can be transmitted both sexually and perinatally. Since syphilis is the second most fatal sexually transmitted disea...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9861075/ https://www.ncbi.nlm.nih.gov/pubmed/36679917 http://dx.doi.org/10.3390/vaccines11010072 |
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author | Khan, Siyab Rizwan, Muhammad Zeb, Adnan Eldeen, Muhammad Alaa Hassan, Said Ur Rehman, Ashfaq A. Eid, Refaat Samir A. Zaki, Mohamed M. Albadrani, Ghadeer E. Altyar, Ahmed Nouh, Nehal Ahmed Talaat Abdel-Daim, Mohamed M. Ullah, Amin |
author_facet | Khan, Siyab Rizwan, Muhammad Zeb, Adnan Eldeen, Muhammad Alaa Hassan, Said Ur Rehman, Ashfaq A. Eid, Refaat Samir A. Zaki, Mohamed M. Albadrani, Ghadeer E. Altyar, Ahmed Nouh, Nehal Ahmed Talaat Abdel-Daim, Mohamed M. Ullah, Amin |
author_sort | Khan, Siyab |
collection | PubMed |
description | Syphilis, a sexually transmitted infection, is a deadly disease caused by Treponema pallidum. It is a Gram-negative spirochete that can infect nearly every organ of the human body. It can be transmitted both sexually and perinatally. Since syphilis is the second most fatal sexually transmitted disease after AIDS, an efficient vaccine candidate is needed to establish long-term protection against infections by T. pallidum. This study used reverse-vaccinology-based immunoinformatic pathway subtractive proteomics to find the best antigenic proteins for multi-epitope vaccine production. Six essential virulent and antigenic proteins were identified, including the membrane lipoprotein TpN32 (UniProt ID: O07950), DNA translocase FtsK (UniProt ID: O83964), Protein Soj homolog (UniProt ID: O83296), site-determining protein (UniProt ID: F7IVD2), ABC transporter, ATP-binding protein (UniProt ID: O83930), and Sugar ABC superfamily ATP-binding cassette transporter, ABC protein (UniProt ID: O83782). We found that the multiepitope subunit vaccine consisting of 4 CTL, 4 HTL, and 11 B-cell epitopes mixed with the adjuvant TLR-2 agonist ESAT6 has potent antigenic characteristics and does not induce an allergic response. Before being docked at Toll-like receptors 2 and 4, the developed vaccine was modeled, improved, and validated. Docking studies revealed significant binding interactions, whereas molecular dynamics simulations demonstrated its stability. Furthermore, the immune system simulation indicated significant and long-lasting immunological responses. The vaccine was then reverse-transcribed into a DNA sequence and cloned into the pET28a (+) vector to validate translational activity as well as the microbial production process. The vaccine developed in this study requires further scientific consensus before it can be used against T. pallidum to confirm its safety and efficacy. |
format | Online Article Text |
id | pubmed-9861075 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-98610752023-01-22 Identification of a Potential Vaccine against Treponema pallidum Using Subtractive Proteomics and Reverse-Vaccinology Approaches Khan, Siyab Rizwan, Muhammad Zeb, Adnan Eldeen, Muhammad Alaa Hassan, Said Ur Rehman, Ashfaq A. Eid, Refaat Samir A. Zaki, Mohamed M. Albadrani, Ghadeer E. Altyar, Ahmed Nouh, Nehal Ahmed Talaat Abdel-Daim, Mohamed M. Ullah, Amin Vaccines (Basel) Article Syphilis, a sexually transmitted infection, is a deadly disease caused by Treponema pallidum. It is a Gram-negative spirochete that can infect nearly every organ of the human body. It can be transmitted both sexually and perinatally. Since syphilis is the second most fatal sexually transmitted disease after AIDS, an efficient vaccine candidate is needed to establish long-term protection against infections by T. pallidum. This study used reverse-vaccinology-based immunoinformatic pathway subtractive proteomics to find the best antigenic proteins for multi-epitope vaccine production. Six essential virulent and antigenic proteins were identified, including the membrane lipoprotein TpN32 (UniProt ID: O07950), DNA translocase FtsK (UniProt ID: O83964), Protein Soj homolog (UniProt ID: O83296), site-determining protein (UniProt ID: F7IVD2), ABC transporter, ATP-binding protein (UniProt ID: O83930), and Sugar ABC superfamily ATP-binding cassette transporter, ABC protein (UniProt ID: O83782). We found that the multiepitope subunit vaccine consisting of 4 CTL, 4 HTL, and 11 B-cell epitopes mixed with the adjuvant TLR-2 agonist ESAT6 has potent antigenic characteristics and does not induce an allergic response. Before being docked at Toll-like receptors 2 and 4, the developed vaccine was modeled, improved, and validated. Docking studies revealed significant binding interactions, whereas molecular dynamics simulations demonstrated its stability. Furthermore, the immune system simulation indicated significant and long-lasting immunological responses. The vaccine was then reverse-transcribed into a DNA sequence and cloned into the pET28a (+) vector to validate translational activity as well as the microbial production process. The vaccine developed in this study requires further scientific consensus before it can be used against T. pallidum to confirm its safety and efficacy. MDPI 2022-12-28 /pmc/articles/PMC9861075/ /pubmed/36679917 http://dx.doi.org/10.3390/vaccines11010072 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Khan, Siyab Rizwan, Muhammad Zeb, Adnan Eldeen, Muhammad Alaa Hassan, Said Ur Rehman, Ashfaq A. Eid, Refaat Samir A. Zaki, Mohamed M. Albadrani, Ghadeer E. Altyar, Ahmed Nouh, Nehal Ahmed Talaat Abdel-Daim, Mohamed M. Ullah, Amin Identification of a Potential Vaccine against Treponema pallidum Using Subtractive Proteomics and Reverse-Vaccinology Approaches |
title | Identification of a Potential Vaccine against Treponema pallidum Using Subtractive Proteomics and Reverse-Vaccinology Approaches |
title_full | Identification of a Potential Vaccine against Treponema pallidum Using Subtractive Proteomics and Reverse-Vaccinology Approaches |
title_fullStr | Identification of a Potential Vaccine against Treponema pallidum Using Subtractive Proteomics and Reverse-Vaccinology Approaches |
title_full_unstemmed | Identification of a Potential Vaccine against Treponema pallidum Using Subtractive Proteomics and Reverse-Vaccinology Approaches |
title_short | Identification of a Potential Vaccine against Treponema pallidum Using Subtractive Proteomics and Reverse-Vaccinology Approaches |
title_sort | identification of a potential vaccine against treponema pallidum using subtractive proteomics and reverse-vaccinology approaches |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9861075/ https://www.ncbi.nlm.nih.gov/pubmed/36679917 http://dx.doi.org/10.3390/vaccines11010072 |
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