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BioImpacts. 2021;11(1): 65-84.
doi: 10.34172/bi.2021.11
PMID: 33469510
PMCID: PMC7803919
Scopus ID: 85099197264
  Abstract View: 1009
  PDF Download: 774

COVID-19

Original Research

A domain-based vaccine construct against SARS-CoV-2, the causative agent of COVID-19 pandemic: development of self-amplifying mRNA and peptide vaccines

Mohammad Mostafa Pourseif 1 ORCID logo, Sepideh Parvizpour 1, Behzad Jafari 2,1, Jaber Dehghani 1 ORCID logo, Behrouz Naghili 3, Yadollah Omidi 4* ORCID logo

1 Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran
2 Department of Medicinal Chemistry, Faculty of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran
3 Research Center for Infectious and Tropical Diseases, Tabriz University of Medical Sciences, Tabriz, Iran
4 Nova Southeastern University, College of Pharmacy, Florida, USA

Abstract

Introduction: Coronavirus disease 2019 (COVID-19) is undoubtedly the most challenging pandemic in the current century with more than 293,241 deaths worldwide since its emergence in late 2019 (updated May 13, 2020). COVID-19 is caused by a novel emerged coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Today, the world needs crucially to develop a prophylactic vaccine scheme for such emerged and emerging infectious pathogens.
Methods: In this study, we have targeted spike (S) glycoprotein, as an important surface antigen to identify its B- and T-cell immunodominant regions. We have conducted a multi-method B-cell epitope (BCE) prediction approach using different predictor algorithms to discover the most potential BCEs. Besides, we sought among a pool of MHC class I and II-associated peptide binders provided by the IEDB server through the strict cut-off values. To design a broad-coverage vaccine, we carried out a population coverage analysis for a set of candidate T-cell epitopes and based on the HLA allele frequency in the top most-affected countries by COVID-19 (update 02 April 2020).
Results: The final determined B- and T-cell epitopes were mapped on the S glycoprotein sequence, and three potential hub regions covering the largest number of overlapping epitopes were identified for the vaccine designing (I531–N711; T717–C877; and V883–E973). Here, we have designed two domain-based constructs to be produced and delivered through the recombinant protein- and gene-based approaches, including (i) an adjuvanted domain-based protein vaccine construct (DPVC), and (ii) a self-amplifying mRNA vaccine (SAMV) construct. The safety, stability, and immunogenicity of the DPVC were validated using the integrated sequential (i.e. allergenicity, autoimmunity, and physicochemical features) and structural (i.e. molecular docking between the vaccine and human Toll-like receptors (TLRs) 4 and 5) analysis. The stability of the docked complexes was evaluated using the molecular dynamics (MD) simulations.
Conclusion: These rigorous in silico validations supported the potential of the DPVC and SAMV to promote both innate and specific immune responses in preclinical studies.

Keywords: COVID-19, Emerging virus, Epitope, SARS-CoV-2, Self-amplifying mRNA vaccine, Spike glycoprotein, Structural modeling, Pandemic
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Abstract View: 1009

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PDF Download: 774

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Submitted: 22 Sep 2020
Revision: 18 Nov 2020
Accepted: 25 Nov 2020
ePublished: 10 Dec 2020
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