Back to Journals » Infection and Drug Resistance » Volume 11

Structural basis of development of multi-epitope vaccine against Middle East respiratory syndrome using in silico approach

Authors Srivastava S, Kamthania M, Singh S, Saxena AK, Sharma N

Received 24 May 2018

Accepted for publication 1 August 2018

Published 21 November 2018 Volume 2018:11 Pages 2377—2391

DOI https://doi.org/10.2147/IDR.S175114

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Professor Suresh Antony


Sukrit Srivastava,1,2 Mohit Kamthania,1,3 Soni Singh,1 Ajay K Saxena,2 Nishi Sharma1

1Department of Biotechnology, Mangalayatan University, Aligarh, India; 2Molecular Medicine Lab, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India; 3Department of Biotechnology, Faculty of Life Sciences, Institute of Applied Medicines and Research, Ghaziabad, Uttar Pradesh, India

Background: Middle East respiratory syndrome (MERS) is caused by MERS coronavirus (MERS-CoV). Thus far, MERS outbreaks have been reported from Saudi Arabia (2013 and 2014) and South Korea (2015). No specific vaccine has yet been reported against MERS.
Purpose: To address the urgent need for an MERS vaccine, in the present study, we have designed two multi-epitope vaccines (MEVs) against MERS utilizing several in silico methods and tools.
Methods: The design of both the multi-epitope vaccines (MEVs) are composed of cytotoxic T lymphocyte (CTL) and helper T lymphocyte (HTL) epitopes, screened form thirteen different proteins of MERS-CoV. Both the MEVs also carry potential B-cell linear epitope regions, B-cell discontinuous epitopes as well as interferon-γ-inducing epitopes. Human β-defensin-2 and β-defensin-3 were used as adjuvants to enhance the immune response of MEVs. To design the MEVs, short peptide molecular linkers were utilized to link screened most potential CTL epitopes, HTL epitopes and the adjuvants. Tertiary models for both the MEVs were generated, refined, and further studied for their molecular interaction with toll-like receptor 3. The cDNAs of both MEVs were generated and analyzed in silico for their expression in a mammalian host cell line (human).
Results: Screened CTL and HTL epitopes were found to have high propensity for stable molecular interaction with HLA alleles molecules. CTL epitopes were also found to have favorable molecular interaction within the cavity of transporter associated with antigen processing. The selected CTL and HTL epitopes jointly cover upto 94.0% of worldwide human population. Both the CTL and HTL MEVs molecular models have shown to have stable binding and complex formation propensity with toll-like receptor 3. The cDNA analysis of both the MEVs have shown high expression tendency in mammalian host cell line (human).
Conclusion: After multistage in silico analysis, both the MEVs are predicted to elicit humoral as well as cell mediated immune response. Epitopes of the designed MEVs are predicted to cover large human population worldwide. Hence both the designed MEVs could be tried in vivo as potential vaccine candidates against MERS.

Keywords: Middle East respiratory syndrome, MERS, Middle East respiratory syndrome coronavirus, MERS-CoV, human transporter associated with antigen processing, TAP, toll-like receptor 3, TLR-3, epitope, immunoinformatics, molecular docking, molecular dynamics simulation, MD simulation, multi-epitope vaccine

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]