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Single-cell transcriptomic atlas of individuals receiving inactivated COVID-19 vaccines reveals distinct immunological responses between vaccine and natural SARS-CoV-2 infection

By Yi Wang, Xiaoxia Wang, Laurence Don Wai Luu, Jieqiong Li, Xiaodai Cui, Hailan Yao, Xin Zhang, Shaojin Chen, Jin Fu, Licheng Wang, Chongzhen Wang, Rui Yuan, Qinguo Cai, Xiaolan Huang, Junfei Huang, Wenjian Xu, Shijun Li, Xiong Zhu, Jun Tai

Posted 31 Aug 2021
medRxiv DOI: 10.1101/2021.08.30.21262863

To control the ongoing COVID-19 pandemic, CoronaVac (Sinovac), an inactivated vaccine, has been granted emergency use authorization by many countries. However, the underlying mechanisms of the inactivated COVID-19 vaccine-induced immune response remain unclear, and little is known about its features compared to SARS-CoV-2 infection. Here, we implemented single-cell RNA sequencing (scRNA-seq) to profile longitudinally collected PBMCs (peripheral blood mononuclear cells) in six individuals immunized with CoronaVac and compared these to the profiles of COVID-19 infected patients from a Single Cell Consortium. Both inactivated vaccines and SARS-CoV-2 infection drove changes in immune cell type proportions, caused B cell activation and differentiation, and induced the expression of genes associated with antibody production in the plasma. The inactivated vaccine and SARS-COV-2 infection also caused alterations in peripheral immune activity such as interferon response, inflammatory cytokine expression, innate immune cell apoptosis and migration, effector T cell exhaustion and cytotoxicity, however, the magnitude of change was greater in COVID-19 patients, especially those with severe disease, than in immunized individuals. Further analyses revealed a distinct peripheral immune cell phenotype associated with CoronaVac immunization (HLA class II upregulation and IL21R upregulation in naive B cells) versus SARS-CoV-2 infection (HLA class II downregulation and IL21R downregulation in naive B cells severe disease). There were also differences in the expression of important genes associated with proinflammatory cytokines and thrombosis. In conclusion, this study provides a single-cell atlas of the systemic immune response to CoronaVac immunization and reveals distinct immune responses between inactivated vaccines and SARS-CoV-2 infection.

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