Cellular basis of enhanced humoral immunity to SARS-CoV-2 upon homologous or heterologous booster vaccination analyzed by single-cell immune profiling

Jingwen Ai; Jingxin Guo; Haocheng Zhang; Yi Zhang; Haochen Yang; Ke Lin; Jieyu Song; Zhangfan Fu; Mingxiang Fan; Qiran Zhang; Hongyu Wang; Yuanhan Zhao; Zhangyufan He; An Cui; Yang Zhou; Jing Wu; Mingzhe Zhou; Guanmin Yuan; Boxi Kang; Ning Zhao; Yuanyuan Xu; Mengqi Zhu; Youhong Wang; Zemin Zhang; Ning Jiang; Chao Qiu; Chenqi Xu; Wenhong Zhang

doi:10.1038/s41421-022-00480-5

Cellular basis of enhanced humoral immunity to SARS-CoV-2 upon homologous or heterologous booster vaccination analyzed by single-cell immune profiling

Cell Discov. 2022 Oct 21;8(1):114. doi: 10.1038/s41421-022-00480-5.

Authors

Jingwen Ai^#^{1

2}, Jingxin Guo^#^{1

2}, Haocheng Zhang^#^{1

2}, Yi Zhang^#^{1

2}, Haochen Yang^#^{3

4}, Ke Lin^#^{1

2}, Jieyu Song^#^{1

2}, Zhangfan Fu^#^{1

2}, Mingxiang Fan^#⁵, Qiran Zhang^{1

2}, Hongyu Wang^{1

2}, Yuanhan Zhao^{1

2}, Zhangyufan He^{1

2}, An Cui^{1

2}, Yang Zhou^{1

2}, Jing Wu^{1

2}, Mingzhe Zhou^{1

2}, Guanmin Yuan^{1

2}, Boxi Kang⁶, Ning Zhao⁶, Yuanyuan Xu^{1

2}, Mengqi Zhu^{1

2}, Youhong Wang^{1

2}, Zemin Zhang⁷, Ning Jiang^{8

9

10}, Chao Qiu^{11

12

13}, Chenqi Xu^{14

15

16}, Wenhong Zhang^{17

18

19

20}

Affiliations

¹ National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
² Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai, China.
³ State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China.
⁴ University of Chinese Academy of Sciences, Beijing, China.
⁵ Department of Urology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China.
⁶ Analytical Biosciences Limited, Beijing, China.
⁷ Biomedical Pioneering Innovation Center (BIOPIC), School of Life Sciences, Peking University, Beijing, China.
⁸ National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China. ningjiang@fudan.edu.cn.
⁹ Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai, China. ningjiang@fudan.edu.cn.
¹⁰ State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China. ningjiang@fudan.edu.cn.
¹¹ National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China. qiuchao@fudan.edu.cn.
¹² Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai, China. qiuchao@fudan.edu.cn.
¹³ Institutes of Biomedical Sciences, Fudan University, Shanghai, China. qiuchao@fudan.edu.cn.
¹⁴ State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China. cqxu@sibcb.ac.cn.
¹⁵ School of Life Science and Technology, ShanghaiTech University, Shanghai, China. cqxu@sibcb.ac.cn.
¹⁶ Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, Zhejiang, China. cqxu@sibcb.ac.cn.
¹⁷ National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China. wenhongzhang_hs@126.com.
¹⁸ Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai, China. wenhongzhang_hs@126.com.
¹⁹ National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China. wenhongzhang_hs@126.com.
²⁰ Huashen Institute of Microbes and Infections, Shanghai, China. wenhongzhang_hs@126.com.

^# Contributed equally.

Abstract

SARS-CoV-2 vaccine booster dose can induce a robust humoral immune response, however, its cellular mechanisms remain elusive. Here, we investigated the durability of antibody responses and single-cell immune profiles following booster dose immunization, longitudinally over 6 months, in recipients of a homologous BBIBP-CorV/BBIBP-CorV or a heterologous BBIBP-CorV/ZF2001 regimen. The production of neutralizing antibodies was dramatically enhanced by both booster regimens, and the antibodies could last at least six months. The heterologous booster induced a faster and more robust plasmablast response, characterized by activation of plasma cells than the homologous booster. The response was attributed to recall of memory B cells and the de novo activation of B cells. Expanded B cell clones upon booster dose vaccination could persist for months, and their B cell receptors displayed accumulated mutations. The production of antibody was positively correlated with antigen presentation by conventional dendritic cells (cDCs), which provides support for B cell maturation through activation and development of follicular helper T (Tfh) cells. The proper activation of cDC/Tfh/B cells was likely fueled by active energy metabolism, and glutaminolysis might also play a general role in promoting humoral immunity. Our study unveils the cellular mechanisms of booster-induced memory/adaptive humoral immunity and suggests potential strategies to optimize vaccine efficacy and durability in future iterations.

Abstract

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