Abstract

Developing an efficacious vaccine for SARS-CoV-2 infection is critical to stemming COVID-19 fatalities and providing the global community with immune protection. We have used a bioinformatic approach to aid in designing an epitope peptide-based vaccine against the spike protein of the virus. Five antigenic B cell epitopes with viable antigenicity and a total of 27 discontinuous B cell epitopes were mapped out structurally in the spike protein for antibody recognition. We identified eight CD8+ T cell 9-mers and 12 CD4+ T cell 14-15-mer as promising candidate epitopes putatively restricted by a large number of MHC I and II alleles, respectively. We used this information to construct an in silico chimeric peptide vaccine whose translational rate was highly expressed when cloned in pET28a (+) vector. With our In silico test, the vaccine construct was predicted to elicit high antigenicity and cell-mediated immunity when given as a homologous prime-boost, triggering of toll-like receptor 5 by the adjuvant linker. The vaccine was also characterized by an increase in IgM and IgG and an array of Th1 and Th2 cytokines. Upon in silico challenge with SARS-CoV-2, there was a decrease in antigen levels using our immune simulations. We, therefore, propose that potential vaccine designs consider this approach.

Highlights

  • An unprecedented pneumonia disease outbreak was reported in late December 2019, after several deaths were recorded in Wuhan, China [1]

  • We considered for further analysis by subjecting the top-scoring predicted epitopes from each tool that have been predicted by five or more different methods and submitted them to Immune-Epitope-Database and Analysis-Resource (IEDB) T cell Class I Immunogenicity predictor

  • The predicted discontinuous epitopes were selected from the entire protein chain component (A, B, and C) of the virus spike protein (PDB: 6VSB), and ranked based on their propensity scores

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Summary

Methods

Structural and physiochemical analysis of SARS-CoV-2 spike proteinThe protein sequence from different geographical regions was retrieved from the NCBI repository with their corresponding accession numbers: Wuhan, China (Genbank ID: QHD43416.1), Japan (Genbank ID: BCA87361.1), California, USA (Genbank ID: QHQ71963.1), Washington, USA (Genbank ID: QHO60594.1), and Valencia, Spain (Genbank ID: QIQ08790.1). Bepipred2.0 executes its operation based on a random forest algorithm trained on epitopes annotated from antibody-antigen protein structures [19] This method is superior to other available tools for sequence-based epitope prediction with regard to both epitope data derived from solved 3D structures and an extensive collection of linear epitopes downloaded from the IEDB database [19]. The following criteria, such as the specificity at 75% and 14–15 mers (residues), binds to various MHC alleles. These conditions are considered when making predictions with the Bepipred linear epitope prediction and Parker hydrophilicity prediction algorithms

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