Screening HLA-A-restricted T cell epitopes of SARS-CoV-2 and the induction of CD8^(+)T cell responses in HLA-A transgenic mice

作     者：Xiaoxiao Jin Yan Ding Shihui Sun Xinyi Wang Zining Zhou Xiaotao Liu Miaomiao Li Xian Chen Anran Shen Yandan Wu Bicheng Liu Jianqiong Zhang Jian Li Yi Yang Haibo Qiu Chuanlai Shen Yuxian He Guangyu Zhao 

作者机构：Department of Microbiology and ImmunologyMedical School of Southeast UniversityNanjing210009JiangsuChina State Key Laboratory of Pathogen and BiosecurityBeijing Institute of Microbiology and EpidemiologyBeijing100071China Blood Component Preparation SectionJiangsu Province Blood CenterNanjing210042JiangsuChina Institute of NephrologyZhongda HospitalMedical School of Southeast UniversityNanjing210009JiangsuChina Life Science&Technology School of Southeast UniversityNanjing210096JiangsuChina Jiangsu Province Key Laboratory of Critical Care MedicineDepartment of Critical Care MedicineZhongda HospitalMedical School of Southeast UniversityNanjing210009JiangsuChina Institute of Pathogen BiologyChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100730China 

出 版 物：《Cellular & Molecular Immunology》 (中国免疫学杂志（英文版）)

年 卷 期：2021年第18卷第12期

页      面：2588-2608页

核心收录：

学科分类：1001[医学-基础医学(可授医学、理学学位)] 100102[医学-免疫学] 10[医学] 

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). 

主　　题：SARS-CoV-2 T cell epitope HLA-A Vaccination 

摘      要：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.