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Cell Surface Fibroblast Activation Protein-2 (Fap2) of Fusobacterium nucleatum as a Vaccine Candidate for Therapeutic Intervention of Human Colorectal Cancer: An Immunoinformatics Approach

Colorectal cancer (CRC) is one of the most common cancers and is the second-highest in cancer-related deaths worldwide. The changes in gut homeostasis and microbial dysbiosis lead to the initiation of the tumorigenesis process. Several pathogenic gram-negative bacteria including Fusobacterium nuclea...

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Autores principales: Padma, Somrita, Patra, Ritwik, Sen Gupta, Parth Sarthi, Panda, Saroj Kumar, Rana, Malay Kumar, Mukherjee, Suprabhat
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10056511/
https://www.ncbi.nlm.nih.gov/pubmed/36992108
http://dx.doi.org/10.3390/vaccines11030525
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author Padma, Somrita
Patra, Ritwik
Sen Gupta, Parth Sarthi
Panda, Saroj Kumar
Rana, Malay Kumar
Mukherjee, Suprabhat
author_facet Padma, Somrita
Patra, Ritwik
Sen Gupta, Parth Sarthi
Panda, Saroj Kumar
Rana, Malay Kumar
Mukherjee, Suprabhat
author_sort Padma, Somrita
collection PubMed
description Colorectal cancer (CRC) is one of the most common cancers and is the second-highest in cancer-related deaths worldwide. The changes in gut homeostasis and microbial dysbiosis lead to the initiation of the tumorigenesis process. Several pathogenic gram-negative bacteria including Fusobacterium nucleatum are the principal contributors to the induction and pathogenesis of CRC. Thus, inhibiting the growth and survival of these pathogens can be a useful intervention strategy. Fibroblast activation protein-2 (Fap2) is an essential membrane protein of F. nucleatum that promotes the adherence of the bacterium to the colon cells, recruitment of immune cells, and induction of tumorigenesis. The present study depicts the design of an in silico vaccine candidate comprising the B-cell and T-cell epitopes of Fap2 for improving cell-mediated and humoral immune responses against CRC. Notably, this vaccine participates in significant protein–protein interactions with human Toll-like receptors, especially with TLR6 reveals, which is most likely to be correlated with its efficacy in eliciting potential immune responses. The immunogenic trait of the designed vaccine was verified by immune simulation approach. The cDNA of the vaccine construct was cloned in silico within the expression vector pET30ax for protein expression. Collectively, the proposed vaccine construct may serve as a promising therapeutic in intervening F. nucleatum-induced human CRC.
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spelling pubmed-100565112023-03-30 Cell Surface Fibroblast Activation Protein-2 (Fap2) of Fusobacterium nucleatum as a Vaccine Candidate for Therapeutic Intervention of Human Colorectal Cancer: An Immunoinformatics Approach Padma, Somrita Patra, Ritwik Sen Gupta, Parth Sarthi Panda, Saroj Kumar Rana, Malay Kumar Mukherjee, Suprabhat Vaccines (Basel) Article Colorectal cancer (CRC) is one of the most common cancers and is the second-highest in cancer-related deaths worldwide. The changes in gut homeostasis and microbial dysbiosis lead to the initiation of the tumorigenesis process. Several pathogenic gram-negative bacteria including Fusobacterium nucleatum are the principal contributors to the induction and pathogenesis of CRC. Thus, inhibiting the growth and survival of these pathogens can be a useful intervention strategy. Fibroblast activation protein-2 (Fap2) is an essential membrane protein of F. nucleatum that promotes the adherence of the bacterium to the colon cells, recruitment of immune cells, and induction of tumorigenesis. The present study depicts the design of an in silico vaccine candidate comprising the B-cell and T-cell epitopes of Fap2 for improving cell-mediated and humoral immune responses against CRC. Notably, this vaccine participates in significant protein–protein interactions with human Toll-like receptors, especially with TLR6 reveals, which is most likely to be correlated with its efficacy in eliciting potential immune responses. The immunogenic trait of the designed vaccine was verified by immune simulation approach. The cDNA of the vaccine construct was cloned in silico within the expression vector pET30ax for protein expression. Collectively, the proposed vaccine construct may serve as a promising therapeutic in intervening F. nucleatum-induced human CRC. MDPI 2023-02-23 /pmc/articles/PMC10056511/ /pubmed/36992108 http://dx.doi.org/10.3390/vaccines11030525 Text en © 2023 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
Padma, Somrita
Patra, Ritwik
Sen Gupta, Parth Sarthi
Panda, Saroj Kumar
Rana, Malay Kumar
Mukherjee, Suprabhat
Cell Surface Fibroblast Activation Protein-2 (Fap2) of Fusobacterium nucleatum as a Vaccine Candidate for Therapeutic Intervention of Human Colorectal Cancer: An Immunoinformatics Approach
title Cell Surface Fibroblast Activation Protein-2 (Fap2) of Fusobacterium nucleatum as a Vaccine Candidate for Therapeutic Intervention of Human Colorectal Cancer: An Immunoinformatics Approach
title_full Cell Surface Fibroblast Activation Protein-2 (Fap2) of Fusobacterium nucleatum as a Vaccine Candidate for Therapeutic Intervention of Human Colorectal Cancer: An Immunoinformatics Approach
title_fullStr Cell Surface Fibroblast Activation Protein-2 (Fap2) of Fusobacterium nucleatum as a Vaccine Candidate for Therapeutic Intervention of Human Colorectal Cancer: An Immunoinformatics Approach
title_full_unstemmed Cell Surface Fibroblast Activation Protein-2 (Fap2) of Fusobacterium nucleatum as a Vaccine Candidate for Therapeutic Intervention of Human Colorectal Cancer: An Immunoinformatics Approach
title_short Cell Surface Fibroblast Activation Protein-2 (Fap2) of Fusobacterium nucleatum as a Vaccine Candidate for Therapeutic Intervention of Human Colorectal Cancer: An Immunoinformatics Approach
title_sort cell surface fibroblast activation protein-2 (fap2) of fusobacterium nucleatum as a vaccine candidate for therapeutic intervention of human colorectal cancer: an immunoinformatics approach
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10056511/
https://www.ncbi.nlm.nih.gov/pubmed/36992108
http://dx.doi.org/10.3390/vaccines11030525
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