Volume 9, Issue 2 (May 2021)                   Res Mol Med (RMM) 2021, 9(2): 119-138 | Back to browse issues page


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Sefid F, Akbari Oryani M, Mehdi M, Payandeh Z, Khalili S, Kaffash E, et al . A Chimeric Vaccine Consisting of Highly Immunogenic Regions Form Escherichia coli Iron Regulated Outer-Membrane Proteins: An In Silico Approach. Res Mol Med (RMM) 2021; 9 (2) :119-138
URL: http://rmm.mazums.ac.ir/article-1-411-en.html
1- Department of Biology Sciences, School of Materials Engineering and Interdisciplinary Sciences, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
2- Department of Pathology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
3- Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, India.
4- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
5- Department of Pharmaceutics, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
6- Department of Mechanical Engineering, Yazd University, Yazd, Iran. , azamirad.Gh@gmail.com
7- Department of Medical Genetics, Shahid Sadoughi University of Medical Science, Yazd, Iran.
Abstract:   (2715 Views)
Background: Six pathogen-associated Outer Membrane Iron receptors (OMPs) reside in Uropathogenic strains of E. coli (UPEC): haem-utilization gene (ChuA), Heme acquisition protein (Hma), IrgA homologue adhesin (Iha), Iron-regulated virulence gene (IreA), IroN, and IutA. Cumulative concern over the prevalence of this bacteria in hospital environments, especially in Intensive Care Units (ICUs), highlights the significance of vaccination against this pathogen. In this study, we aimed to develop 3D models of ChuA, Hma, IutA, IreA, Iha, and IroN proteins by invoking various in silico methods and design a chimeric immunogen composed of highly immunogenic regions from these six Escherichia coli antigens as a chimeric vaccine.
Materials and Methods: In the present study, homology modeling, fold recognition, Ab initio approaches, and their combination were invoked to determine the Three-Dimensional (3D) structures of ChuA, Hma, Iha, IreA, IroN, and IutA. Next, a set of biochemical, immunological, and functional properties were predicted using various bioinformatics tools.
Results: The obtained results indicated that all six modeled proteins fold to a β-barrel structure. The results of biochemical, immunological, and functional analysis determined the regions of each antigen carrying the best immunogenic properties. These regions are employed to construct the final vaccine linked via flexible GGGGS linkers. Intriguingly, re-analyzing the properties of the final vaccine indicated its immunological advantage over individual proteins. 
Conclusion: The strategy of this study to predict the protein 3D structure, followed by epitope prediction, could be adapted to design efficient vaccine candidates. Applying this approach, we designed a vaccine candidate harboring the most promising regions of six OMPs. This approach could lead to better functional, structural, and therapeutic outcomes in the context of vaccine design investigations.
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Type of Study: Research | Subject: Immunology
Published: 2021/05/20

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