Integrative immunoinformatics paradigm for predicting potential B-cell and T-cell epitopes as viable candidates for subunit vaccine design against COVID-19 virulence

BACKGROUND: The increase in global mortality rates from SARS-COV2 (COVID-19) infection has been alarming thereby necessitating the continual search for viable therapeutic interventions. Due to minimal microbial components, subunit (peptide-based) vaccines have demonstrated improved efficacies in stimulating immunogenic responses by host B- and T-cells. METHODS: Integrative immunoinformatics algorithms were used to determine linear and discontinuous B-cell epitopes from the S-glycoprotein sequence. End-point selection of the most potential B-cell epitope was based on highly essential physicochemical attributes. NetCTL-I and NetMHC-II algorithms were used to predict probable MHC-I and II T-cell epitopes for globally frequent HLA-A∗O2:01, HLA-B∗35:01, HLA-B∗51:01 and HLA-DRB1∗15:02 molecules. Highly probable T-cell epitopes were selected based on their high propensities for C-terminal cleavage, transport protein (TAP) processing and MHC-I/II binding. RESULTS: Preferential epitope binding sites were further identified on the HLA molecules using a blind peptide-docking method. Phylogenetic analysis revealed close relativity between SARS-CoV-2 and SARS-CoV S-protein. LALHRSYLTPGDSSSGWTAGAA(242→263) was the most probable B-cell epitope with optimal physicochemical attributes. MHC-I antigenic presentation pathway was highly favourable for YLQPRTFLL(269-277) (HLA-A∗02:01), LPPAYTNSF(24-32) (HLA-B∗35:01) and IPTNFTISV7(14-721) (HLA-B∗51:01). Also, LTDEMIAQYTSALLA(865-881) exhibited the highest binding affinity to HLA-DR B1∗15:01 with core interactions mediated by IAQYTSALL(870-878). COVID-19 YLQPRTFLL(269-277) was preferentially bound to a previously undefined site on HLA-A∗02:01 suggestive of a novel site for MHC-I-mediated T-cell stimulation. CONCLUSION: This study implemented combinatorial immunoinformatics methods to model B- and T-cell epitopes with high potentials to trigger immunogenic responses to the S protein of SARS-CoV-2.