Abstract
Our research is driven by the need to design an advanced multi-epitope vaccine construct (MEVC) using the S-protein of SARS-CoV-2 to combat the emergence of new variants. Through rigorous computational screening, we have identified linear and discontinuous B-cell epitopes, CD8 + and CD4 + T-cell epitopes, ensuring extensive MEVC coverage across 90.03% of the global population. The MEVC, featuring four CD4 + and four CD8 + T-cell epitopes connected linearly with two adjuvant proteins on both ends, has been carefully designed to elicit robust immune response. Our in-silico analysis has confirmed the construct's antigenicity, non-allergenicity, and non-toxicity with optimized codon sequences for enhanced expression in E. coli K12. Furthermore, molecular docking and dynamics analyses have demonstrated its strong binding affinity with TLR-3 and TLR 4, and in-silico immune simulation yielded promising results on heightened B-cell and T-cell-mediated immunity. However, wet lab experiments are essential to validate computational findings to revolutionize the development of vaccines against SARS-CoV-2.