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Designing a Fusion Protein Vaccine Against HCV: An In Silico Approach

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Abstract

Hepatitis C virus (HCV) infection is a major global issue that leads to serious liver disease such as chronic liver inflammation and hepatocellular carcinoma. At present, no approved vaccine is available for control or treatment of HCV infection. Therefore, the development of an efficient vaccine against HCV is an urgent need. Today, designing an effective vaccine against hepatitis C is one of the outmost propriety for researchers. Fusion protein vaccines containing the immunogen proteins and adjuvant molecules are able to stimulate both humoral and cellular responses that are crucial for eradicating HCV infection. Herein, in silico design of fusion forms of vaccine candidates against HCV, including flagellin (fliC) from Pseudomonas aeruginosa and NS5B antigen (NT300) from HCV was performed. First, two forms of fusion protein (NT300-fliC and fliC-NT300) were designed and analyzed using different bioinformatics tools. For this aim, the Iterative threading assembly refinement (I-TASSER) server was used for modeling the fusion forms of protein; namely, NT300-fliC and fliC-NT300, then the high-rank 3D model of fusion protein was selected, subsequently various physico-chemical, and structural parameters were examined bioinformatically. After the selection of the best construct (fliC-NT300), the interaction of flagellin part of vaccine with toll-like receptor 5 (TLR5) was evaluated via docking studies. Our results represented that based on data obtained from various servers, and the docking analyses of two constructs, fliC-NT300 fusion form showed better results than NT300-fliC. For this reason, the fliC-NT300 form was selected for further evaluations. In sum, structural and immunological computational studies showed that the fliC-NT300 can be introduced as a prophylactic or therapeutic candidate vaccine against the HCV, after the efficacy of that was confirmed via in vitro and in vivo assays.

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Acknowledgements

The present article was extracted from the PhD thesis written by Amir Atapour and was financially supported by Shiraz University of Medical Sciences Grant Number 93-7369.

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Authors and Affiliations

  1. Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran

    Amir Atapour, Pooneh Mokarram, Zohreh MostafaviPour, Younes Ghasemi & Shiva Mohammadi

  2. Department of Biochemistry and Colorectal Research Center, Namazi Hospital, Shiraz University of Medical Sciences, Shiraz, Iran

    Pooneh Mokarram

  3. Department of Bacteriology and Virology, Shiraz University of Medical Sciences, Shiraz, Iran

    Seyed Younes Hosseini

  4. Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Younes Ghasemi & Navid Nezafat

  5. Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

    Younes Ghasemi & Navid Nezafat

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  1. Amir Atapour
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  2. Pooneh Mokarram
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  3. Zohreh MostafaviPour
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  4. Seyed Younes Hosseini
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  7. Navid Nezafat
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Correspondence to Pooneh Mokarram or Navid Nezafat.

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Atapour, A., Mokarram, P., MostafaviPour, Z. et al. Designing a Fusion Protein Vaccine Against HCV: An In Silico Approach. Int J Pept Res Ther 25, 861–872 (2019). https://doi.org/10.1007/s10989-018-9735-4

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