Immunogenicity Validation of Predicted HLA Class II-binding Peptides Derived from SARS-CoV-2 Structural Proteins on Indonesian Population

Abstract

SARS-CoV-2, the cause of the COVID-19 pandemic, prompted rapid vaccine development. However, emerging variants challenge antibody-mediated protection. Targeting T-cell immunity is promising due to its crucial role in eliminating infected cells and the difficulty of viral evasion via HLA diversity. Despite this potential, there is a lack of HLA studies and SARS-CoV-2 epitope mapping in the Indonesian population. Methods: This study enrolled 60 participants from the Indonesian population to evaluate the immunogenicity of 10 SARS-CoV-2 peptides that were predicted to bind to HLA class II alleles of the Indonesian population. Six peptides were from nucleocapsid protein (NP), two from spike (S), one from envelope (E), and one from membrane (M). Three peptides (NP_263-280, S_313-330, and E_46-60) were reported in the Immune Epitope Database (IEDB). Immunogenicity was validated using ELISpot IFN-γ assay on 48 PBMC samples. ELISA measured anti-SARS-CoV-2 (N) IgG antibody levels on 56 serum samples. Results: ELISpot validated the immunogenicity of the 10 peptides, with the newly identified epitope NP_104-122 emerging as a promising representative epitope for the Indonesian population. The ELISpot assay displayed a trend of T cell increase over time, potentially indicating unreported reinfections. Interestingly, while T-cell responses increased over time, there was a significant decline in antibody concentrations. Conclusion: This research establishes the groundwork for SARS-CoV-2 epitope mapping in Indonesians through successfully validating SARS-CoV-2 peptides' immunogenicity. The findings emphasize the importance of T cell-mediated long-term immunity in combating SARS-CoV-2, especially in the face of emerging variants that may evade antibody responses.