The 18th of May 2023, Immunitrack published an original study in Frontiers in Immunology that highlights the importance of peptide-HLA stability in the identification of immunogenic epitopes from SARS-CoV-2.
Summary of the article
The SARS-CoV-2 pandemic stressed the need for having the infrastructure and tools to rapidly develop effective vaccines with a broad coverage. One of the determining factors for designing an effective vaccine is to identify the epitopes with the highest potential of inducing a strong and lasting immune response. A common way of selecting epitopes is to use online tools that report the immunogenicity of an epitope based on the predicted affinity between the epitope and an HLA molecule of interest (the pHLA affinity). However, considering the predicted pHLA affinity alone when selecting an epitope is known to generate a high false discovery rate. For this reason, Immunitrack and collaborators wanted to explore if the stability of the pHLA complex is a better indicator for immunogenicity and thus a stronger selection parameter to consider when choosing epitopes for a therapy, for example a vaccine.
To investigate this hypothesis, the pHLA complex stability was measured across three common class I alleles in Europe (HLA-A*0101, -A*0201 and -A*0301) and 1286 overlapping 9-mer peptides derived from the SARS-CoV-2 Spike protein. The epitopes that formed the most stable pHLA complexes were further investigated for their ability to induce T cell activation compared to epitopes with a low measured pHLA stability. The immunogenicity was assessed by peptide stimulation of peripheral blood mononuclear cells (PBMCs) from vaccinated or convalescent donors followed by measurement of proinflammatory cytokine production as an indicator for CD8+ T cell activation. The results demonstrated that the pHLA complex stability strongly selects for immunogenic epitopes able to activate functional CD8+ T cells. This was observed across the three studied HLA alleles and in both vaccinated and convalescent COVID-19 donors.