Vol. 6, Issue 1, Part A (2024)

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its evolving variants has challenged the efficacy of current vaccines, urging the scientific community to pursue a broad-spectrum vaccine design strategy. This study focuses on the comprehensive epitope mapping of the SARS-CoV-2 spike (S) protein to identify conserved, immunodominant epitopes capable of eliciting cross-protective immunity across major variants of concern (VOCs), including Alpha, Beta, Delta, and Omicron. Using in silico immunoinformatics tools, combined with experimental validation from published neutralization assays and structural analyses, we identified multiple B-cell and T-cell epitopes in the S1 and S2 subunits. Key epitopes were selected based on conservation score, antigenicity, and MHC-binding affinity across HLA alleles. Structural modeling confirmed surface accessibility and conformational stability of dominant epitopes. These findings lay the foundation for designing a next-generation multivalent vaccine targeting conserved regions of the S protein. Such rational design may enhance cross-reactive immune responses and improve vaccine resilience against emerging variants.