| 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 April 2, 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. |