Predicting potential epitopes of structural proteins for Alpha, Delta, and Omicron variants of SARS-CoV-2

Abstract Background Due to the emergence of highly transmissible variants, such as the recombinant subvariant XEC, SARS-CoV-2 continues to spread worldwide. Epitope-based vaccines have been developed since conventional antigen-based vaccines may not provide protection against all SARS-CoV-2 variants. These vaccines target multiple epitopes that interact with antibodies or T-cell receptors and are being investigated to enhance immune responses. Objective This study investigates the spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins of SARS-CoV-2 across different variants, including Alpha, Delta, and Omicron, to identify potential epitopes that could contribute to the development of next-generation vaccines. Methods This study used several freely accessible web-based tools and open source to identify the potential epitopes. Antigenicity, allergenicity, and toxicity prediction were evaluated using VaxiJen v2.0, AntigenPro, AllerTop v2.0, and ToxinPred. Cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL), and linear B lymphocyte (LBL) epitopes were predicted using the Immune Epitope Database (IEDB) server. Results VaxiJen v2.0 indicated that the E protein demonstrates lower antigenicity than the S, M, and N proteins among the selected variants. AntigenPro analysis revealed that in the Alpha (B.1), Delta (AY.23), and Omicron (BQ.1.23) variants, only the S and N proteins surpassed the antigenicity threshold. However, in the Omicron BA.5.2 and BA.1.1 variants, only the E protein was found to be below the threshold. Further analysis showed that only the S (17 CTL, 6 HTL, and 13 LBL) and N (7 CTL, 6 HTL, and 1 LBL) proteins contain potential T-and B-cell epitopes. Conclusions This study provides valuable insights into potential epitopes derived from various SARS-CoV-2 variants, which may be utilized for the development of epitope-based vaccines.