New Omicron mutations enhance the immune response and may explain the decrease in mortality from COVID-19

The journal iScience has published the article “Mutational pressure promotes release of public CD8+ T cell epitopes by proteasome from SARS-CoV-2 RBD of Omicron and its current lineages”, co-authored by a NOVEL researcher.

This study demonstrates that mutations in the Omicron B.1.1.529 variant significantly enhance the release of two immunodominant HLA class I epitopes: 504-GHQPYRVVVL-513 and 496-SFRPTYGVGH-505. These epitopes are generated through the efficient processing—hydrolysis—of the receptor-binding domain (RBD) by both constitutive proteasomes (c20S) and immune proteasomes (i20S). These proteasomes break down the protein into antigenic fragments, which are then presented to the immune system to trigger a protective response.

The authors highlight the global significance of HLA haplotypes capable of presenting these epitopes. Key HLA molecules, such as HLA-B07:02, HLA-B08:01, HLA-B51:01, HLA-C01:02, HLA-C06:02, and HLA-C07:02, are widely distributed among populations and cover up to 82% and 27% of the global population for the 504-GHQPYRVVVL-513 and 496-SFRPTYGVGH-505 epitopes, respectively. This explains the decrease in COVID-19 mortality rates in regions with a high prevalence of these haplotypes after December 2021, when Omicron became the dominant and persistent strain.

The full text article is here https://www.cell.com/iscience/fulltext/S2589-0042(25)00133-6.