Development of multi-epitope mRNA vaccine against Clostridioides difficile using reverse vaccinology and immunoinformatics approaches

Bibliographic Details
Title: Development of multi-epitope mRNA vaccine against Clostridioides difficile using reverse vaccinology and immunoinformatics approaches
Authors: Caixia Tan, Yuanyuan xiao, Ting Liu, Siyao Chen, Juan Zhou, Sisi Zhang, Yiran Hu, Anhua Wu, Chunhui Li
Source: Synthetic and Systems Biotechnology, Vol 9, Iss 4, Pp 667-683 (2024)
Publisher Information: KeAi Communications Co., Ltd., 2024.
Publication Year: 2024
Collection: LCC:Biotechnology
LCC:Biology (General)
Subject Terms: Clotridioides difficile (C. difficile), mRNA vaccine, Immunoinformatics, Reverse vaccinology (RV), Molecular docking, Molecular dynamics (MD) simulation, Biotechnology, TP248.13-248.65, Biology (General), QH301-705.5
More Details: Clostridioides difficile (C. difficile), as the major pathogen of diarrhea in healthcare settings, has become increasingly prevalent within community populations, resulting in significant morbidity and mortality. However, the therapeutic options for Clostridioides difficile infection (CDI) remain limited, and as of now, no authorized vaccine is available to combat this disease. Therefore, the development of a novel vaccine against C. difficile is of paramount importance. In our study, the complete proteome sequences of 118 strains of C. difficile were downloaded and analyzed. We found four antigenic proteins that were highly conserved and can be used for epitope identification. We designed two vaccines, WLcd1 and WLcd2, that contain the ideal T-cell and B-cell epitopes, adjuvants, and the pan HLA DR-binding epitope (PADRE) sequences. The biophysical and chemical assessments of these vaccine candidates indicated that they were suitable for immunogenic applications. Molecular docking analyses revealed that WLcd1 bonded with higher affinity to Toll-like receptors (TLRs) than WLcd2. Furthermore, molecular dynamics (MD) simulations, performed using Gmx_MMPBSA v1.56, confirmed the binding stability of WLcd1 with TLR2 and TLR4. The preliminary findings suggested that this multi-epitope vaccine could be a promising candidate for protection against CDI; however, experimental studies are necessary to confirm these predictions.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2405-805X
Relation: http://www.sciencedirect.com/science/article/pii/S2405805X24000838; https://doaj.org/toc/2405-805X
DOI: 10.1016/j.synbio.2024.05.008
Access URL: https://doaj.org/article/ede1e7e75c9c4974a80471ddddb1b104
Accession Number: edsdoj.1e7e75c9c4974a80471ddddb1b104
Database: Directory of Open Access Journals
More Details
ISSN:2405805X
DOI:10.1016/j.synbio.2024.05.008
Published in:Synthetic and Systems Biotechnology
Language:English