Gao Feng-Xia, Wu Rui-Xin, Shen Mei-Ying, Huang Jing-Jing, Li Ting-Ting, Hu Chao, Luo Fei-Yang, Song Shu-Yi, Mu Song, Hao Ya-Nan, Han Xiao-Jian, Wang Ying-Ming, Li Luo, Li Sheng-Long, Chen Qian, Wang Wang, Jin Ai-Shun
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.
iScience. 2022 Dec 22;25(12):105479. doi: 10.1016/j.isci.2022.105479. Epub 2022 Nov 2.
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 CD8T 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.
面对不断出现具有中和逃逸突变的SARS-CoV-2变体，疫苗加强针的重复接种问题被提了出来，但其保护效果和潜在不良反应在很大程度上仍不清楚。在此，我们在Balb/c小鼠模型中比较了延长疗程的重组受体结合域（RBD）疫苗加强针与传统免疫策略的体液和细胞免疫反应。传统疫苗接种疗程后的多次疫苗加强针显著降低了RBD特异性抗体滴度以及针对Delta和Omicron变体的血清中和效力，并严重损害了CD4和CD8 T细胞的活化，增加了这些T细胞中PD-1和LAG-3的表达。从机制上讲，我们证实延长RBD加强针接种通过促进适应性免疫耐受颠覆了保护性免疫记忆。我们的研究结果表明持续使用SARS-CoV-2疫苗加强针存在潜在风险，为全球新冠疫苗加强接种策略提供了即时启示。
