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. Integrative immunoinformatics algorithms were used to determine linear and discontinuous B-cell epitopes from the S-glycoprotein sequence. End-point

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... n 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. 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. LALHRSYLTPGDSSSGWTAGAA242→263 was the most probable B-cell epitope with optimal physicochemical attributes. MHC-I antigenic presentation pathway was highly favourable for YLQPRTFLL269-277 (HLA-A∗02:01), LPPAYTNSF24-32 (HLA-B∗35:01) and IPTNFTISV714-721 (HLA-B∗51:01). Also, LTDEMIAQYTSALLA865-881 exhibited the highest binding affinity to HLA-DR B1∗15:01 with core interactions mediated by IAQYTSALL870-878. COVID-19 YLQPRTFLL269-277 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. 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.