Construction and efficacy testing of DNA vaccines containing HLA-A^(*)02:01-restricted SARS-CoV-2 T-cell epitopes predicted by immunoinformatics  

作　　者：Dan Tan Ning Kang Yuanfei Zhu Jia Hou Hanqing Wang Huijun Xu Cheng Zu Zixiang Gao Mu Liu Nannan Liu Qiang Deng Hongzhou Lu Jing Liu Youhua Xie 无 

机构地区：[1]Key Laboratory of Medical Molecular Virology(NHC&MOE&CAMS),Shanghai Institute of Infectious Diseases and Biosecurity,Department of Medical Microbiology and Parasitology,School of Basic Medical Sciences,Shanghai Medical College,Fudan University,Shanghai 200031,China [2]Shanghai Public Health Clinical Center,Fudan University,Shanghai 201508,China [3]Department of Clinical Laboratory,Children’s Hospital,Fudan University,Shanghai 201102,China [4]National Clinical Research Centre for Infectious Diseases,the Third People’s Hospital of Shenzhen,The Second Affiliated Hospital of Southern University of Science and Technology,Shenzhen 518112,China

出　　处：《Acta Biochimica et Biophysica Sinica》2024年第7期986-996,共11页生物化学与生物物理学报（英文版）

基　　金：supported by the grants from the Shanghai Municipal Science and Technology Major Project,the National Key R&D Program(No.2023YFC0872600);the National Natural Science Foundation of China(No.81971921).

摘　　要：Vaccines play essential roles in the fight against the COVID-19 pandemic.The development and assessment of COVID-19 vaccines have generally focused on the induction and boosting of neutralizing antibodies targeting the SARS-CoV-2 spike(S)protein.Due to rapid and continuous variation in the S protein,such vaccines need to be regularly updated to match newly emerged dominant variants.T-cell vaccines that target MHC I-or II-restricted epitopes in both structural and non-structural viral proteins have the potential to induce broadly cross-protective and long-lasting responses.In this work,the entire proteome encoded by SARS-CoV-2(Wuhan-hu-1)is subjected to immunoinformatics-based prediction of HLA-A^(*)02:01-restricted epitopes.The immunogenicity of the predicted epitopes is evaluated using peripheral blood mononuclear cells from convalescent Wuhan-hu-1-infected patients.Furthermore,predicted epitopes that are conserved across major SARS-CoV-2 lineages and variants are used to construct DNA vaccines expressing multi-epitope polypeptides.Most importantly,two DNA vaccine constructs induce epitope-specific CD8^(+)T-cell responses in a mouse model of HLA-A^(*)02:01 restriction and protect immunized mice from challenge with Wuhan-hu-1 virus after hACE2 transduction.These data provide candidate T-cell epitopes useful for the development of T-cell vaccines against SARS-CoV-2 and demonstrate a strategy for quick T-cell vaccine candidate development applicable to other emerging pathogens.

关 键 词：COVID-19 cellular immune response CD8^(+)T cell SARS-CoV-2 DNA vaccine 

分 类 号：R392[医药卫生—免疫学] R563.1[医药卫生—基础医学]