SARS-CoV-2 spike protein-derived immunogenic peptides that are promiscuously presented by several HLA-class II molecules and their potential for inducing acquired immunity

The current coronavirus disease 2019 (COVID-19) pandemic that is caused by the severe acute respiratory syndrome 2 (SARS-CoV-2) has a significant threat to public health. Although vaccines based on mRNA of SARS-CoV-2 spike protein have been developed induce both cellular and humoral immunity against SARS-CoV-2, there some concerns raised about their high cost, particularly in developing countries. In present study, we aim identify an immunogenic peptide activate immunity, CD4+ helper T lymphocytes (Th cells), which are commander immune system. protein-derived peptides Spike448-477 Spike489-513(N501Y)-specific Th cell lines were generated repetitive stimulation healthy donor-derived CD4+T-cells with each peptide. Their HLA-restrictions addressed using blocking antibodies HLA HLA-transfected L-cells. epitopes Spike448-477-specific defined series 7–14-mer overlapping truncated alanine-substituted epitope peptides. To address responsiveness these several variants, stimulated mutated We whether identified useful for monitoring T-cell-based responses vaccinated donors IFN-γ ELISpot assay. was found be promiscuous presented HLA- DRB1*08:02, DR53, DPB1*02:02. HLA-DPB1*02:02-restricted cells did not response L452R L452Q mutations, other affected any mutant two tetramers detect HLA-DRB1*08:02/Spike449-463- Spike449-463(L452R/Y453F)-recognizing cells. Spike489-513(N501Y) also promiscuously HLA-DRB1*09:01 DRB1*15:02. T-cell specific Spike489-513 detected PBMCs after vaccinations. addition, observed activated CD8+ T-cells individuals receiving vaccines. peptides, Spike489-513, include multiple HLA-class II alleles cells, considered establishment acquired vaccination.