Since severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)-specific T cells have been found to play essential roles in host immune protection and pathology in patients with coronavirus disease 2019(COVID-19),th...Since severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)-specific T cells have been found to play essential roles in host immune protection and pathology in patients with coronavirus disease 2019(COVID-19),this study focused on the functional validation of T cell epitopes and the development of vaccines that induce specific T cell responses.A total of 120 CD8^(+)T cell epitopes from the E,M,N,S,and RdRp proteins were functionally validated.Among these,110,15,6,14,and 12 epitopes were highly homologous with SARS-CoV,OC43,NL63,HKU1,and 229E,respectively;in addition,four epitopes from the S protein displayed one amino acid that was distinct from the current SARS-CoV-2 variants.Then,31 epitopes restricted by the HLA-A2 molecule were used to generate peptide cocktail vaccines in combination with Poly(I:C),R848 or poly(lactic-co-glycolic acid)nanoparticles,and these vaccines elicited robust and specific CD8^(+)T cell responses in HLA-A2/DR1 transgenic mice as well as wild-type mice.In contrast to previous research,this study established a modified DC-peptide-PBL cell coculture system using healthy donor PBMCs to validate the in silico predicted epitopes,provided an epitope library restricted by nine of the most prevalent HLA-A allotypes covering broad Asian populations,and identified the HLA-A restrictions of these validated epitopes using competitive peptide binding experiments with HMy2.CIR cell lines expressing the indicated HLA-A allotype,which initially confirmed the in vivo feasibility of 9-or 10-mer peptide cocktail vaccines against SARS-CoV-2.These data will facilitate the design and development of vaccines that induce antiviral CD8^(+)T cell responses in COVID-19 patients.展开更多
基金This work was supported by the National Nature Science Foundation of China(82041006)the COVID-19 Emergency Research Fund of Zhejiang University of China(2020XGZX021).
文摘Since severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)-specific T cells have been found to play essential roles in host immune protection and pathology in patients with coronavirus disease 2019(COVID-19),this study focused on the functional validation of T cell epitopes and the development of vaccines that induce specific T cell responses.A total of 120 CD8^(+)T cell epitopes from the E,M,N,S,and RdRp proteins were functionally validated.Among these,110,15,6,14,and 12 epitopes were highly homologous with SARS-CoV,OC43,NL63,HKU1,and 229E,respectively;in addition,four epitopes from the S protein displayed one amino acid that was distinct from the current SARS-CoV-2 variants.Then,31 epitopes restricted by the HLA-A2 molecule were used to generate peptide cocktail vaccines in combination with Poly(I:C),R848 or poly(lactic-co-glycolic acid)nanoparticles,and these vaccines elicited robust and specific CD8^(+)T cell responses in HLA-A2/DR1 transgenic mice as well as wild-type mice.In contrast to previous research,this study established a modified DC-peptide-PBL cell coculture system using healthy donor PBMCs to validate the in silico predicted epitopes,provided an epitope library restricted by nine of the most prevalent HLA-A allotypes covering broad Asian populations,and identified the HLA-A restrictions of these validated epitopes using competitive peptide binding experiments with HMy2.CIR cell lines expressing the indicated HLA-A allotype,which initially confirmed the in vivo feasibility of 9-or 10-mer peptide cocktail vaccines against SARS-CoV-2.These data will facilitate the design and development of vaccines that induce antiviral CD8^(+)T cell responses in COVID-19 patients.
