Extended SARS-CoV-2 RBD booster vaccination induces humoral and cellular immune tolerance in mice
Feng-Xia Gao,
Rui-Xin Wu,
Mei-Ying Shen,
Jing-Jing Huang,
Ting-Ting Li,
Chao Hu,
Fei-Yang Luo,
Shu-Yi Song,
Song Mu,
Ya-Nan Hao,
Xiao-Jian Han,
Ying-Ming Wang,
Luo Li,
Sheng-Long Li,
Qian Chen,
Wang Wang,
Ai-Shun Jin
Affiliations
Feng-Xia Gao
Department of Immunology, College of Basic Medicine, Chongqing Medical University, ChongQing 400010, China; Chongqing Key Laboratory of Basic and Translational Research of Tumor Immunology, Chongqing Medical University, ChongQing 400010, China
Rui-Xin Wu
Department of Immunology, College of Basic Medicine, Chongqing Medical University, ChongQing 400010, China; Chongqing Key Laboratory of Basic and Translational Research of Tumor Immunology, Chongqing Medical University, ChongQing 400010, China
Mei-Ying Shen
Department of Endocrine Breast Surgery, the First Affiliated Hospital of Chongqing Medical University, ChongQing 400010, China
Jing-Jing Huang
Department of Immunology, College of Basic Medicine, Chongqing Medical University, ChongQing 400010, China; Chongqing Key Laboratory of Basic and Translational Research of Tumor Immunology, Chongqing Medical University, ChongQing 400010, China
Ting-Ting Li
Department of Immunology, College of Basic Medicine, Chongqing Medical University, ChongQing 400010, China; Chongqing Key Laboratory of Basic and Translational Research of Tumor Immunology, Chongqing Medical University, ChongQing 400010, China
Chao Hu
Department of Immunology, College of Basic Medicine, Chongqing Medical University, ChongQing 400010, China; Chongqing Key Laboratory of Basic and Translational Research of Tumor Immunology, Chongqing Medical University, ChongQing 400010, China
Fei-Yang Luo
Department of Immunology, College of Basic Medicine, Chongqing Medical University, ChongQing 400010, China; Chongqing Key Laboratory of Basic and Translational Research of Tumor Immunology, Chongqing Medical University, ChongQing 400010, China
Shu-Yi Song
Department of Immunology, College of Basic Medicine, Chongqing Medical University, ChongQing 400010, China; Chongqing Key Laboratory of Basic and Translational Research of Tumor Immunology, Chongqing Medical University, ChongQing 400010, China
Song Mu
Department of Immunology, College of Basic Medicine, Chongqing Medical University, ChongQing 400010, China; Chongqing Key Laboratory of Basic and Translational Research of Tumor Immunology, Chongqing Medical University, ChongQing 400010, China
Ya-Nan Hao
Department of Immunology, College of Basic Medicine, Chongqing Medical University, ChongQing 400010, China; Chongqing Key Laboratory of Basic and Translational Research of Tumor Immunology, Chongqing Medical University, ChongQing 400010, China
Xiao-Jian Han
Department of Immunology, College of Basic Medicine, Chongqing Medical University, ChongQing 400010, China; Chongqing Key Laboratory of Basic and Translational Research of Tumor Immunology, Chongqing Medical University, ChongQing 400010, China
Ying-Ming Wang
Department of Immunology, College of Basic Medicine, Chongqing Medical University, ChongQing 400010, China; Chongqing Key Laboratory of Basic and Translational Research of Tumor Immunology, Chongqing Medical University, ChongQing 400010, China
Luo Li
Department of Immunology, College of Basic Medicine, Chongqing Medical University, ChongQing 400010, China; Chongqing Key Laboratory of Basic and Translational Research of Tumor Immunology, Chongqing Medical University, ChongQing 400010, China
Sheng-Long Li
Department of Immunology, College of Basic Medicine, Chongqing Medical University, ChongQing 400010, China; Chongqing Key Laboratory of Basic and Translational Research of Tumor Immunology, Chongqing Medical University, ChongQing 400010, China
Qian Chen
Department of Immunology, College of Basic Medicine, Chongqing Medical University, ChongQing 400010, China; Chongqing Key Laboratory of Basic and Translational Research of Tumor Immunology, Chongqing Medical University, ChongQing 400010, China
Wang Wang
Department of Immunology, College of Basic Medicine, Chongqing Medical University, ChongQing 400010, China; Chongqing Key Laboratory of Basic and Translational Research of Tumor Immunology, Chongqing Medical University, ChongQing 400010, China; Corresponding author
Ai-Shun Jin
Department of Immunology, College of Basic Medicine, Chongqing Medical University, ChongQing 400010, China; Chongqing Key Laboratory of Basic and Translational Research of Tumor Immunology, Chongqing Medical University, ChongQing 400010, China; Corresponding author
Summary: The repetitive applications of vaccine boosters have been brought up in face of continuous emergence of SARS-CoV-2 variants with neutralization escape mutations, but their protective efficacy and potential adverse effects remain largely unknown. Here, we compared the humoral and cellular immune responses of an extended course of recombinant receptor binding domain (RBD) vaccine boosters with those from conventional immunization strategy in a Balb/c mice model. Multiple vaccine boosters after the conventional vaccination course significantly decreased RBD-specific antibody titers and serum neutralizing efficacy against the Delta and Omicron variants, and profoundly impaired CD4+ and CD8+T cell activation and increased PD-1 and LAG-3 expressions in these T cells. Mechanistically, we confirmed that extended vaccination with RBD boosters overturned the protective immune memories by promoting adaptive immune tolerance. Our findings demonstrate potential risks with the continuous use of SARS-CoV-2 vaccine boosters, providing immediate implications for the global COVID-19 vaccination enhancement strategies.
