Diverse BCR usage and T cell activation induced by different COVID-19 sequential vaccinations
Junxiang Wang,
Kaiyi Li,
Yuan Wang,
Zhengfang Lin,
Weidong Li,
Jinpeng Cao,
Xinyue Mei,
Rui Wei,
Jinglu Yang,
Xiaobing Zhai,
Deyi Huang,
Kaiwen Zhou,
Xinyue Liang,
Zhongfang Wang
Affiliations
Junxiang Wang
State Key Laboratory of Respiratory Disease and National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China
Kaiyi Li
State Key Laboratory of Respiratory Disease and National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China
Yuan Wang
State Key Laboratory of Respiratory Disease and National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China
Zhengfang Lin
State Key Laboratory of Respiratory Disease and National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China
Weidong Li
State Key Laboratory of Respiratory Disease and National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China
Jinpeng Cao
State Key Laboratory of Respiratory Disease and National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China
Xinyue Mei
State Key Laboratory of Respiratory Disease and National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China
Rui Wei
State Key Laboratory of Respiratory Disease and National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China
Jinglu Yang
Guangzhou National Laboratory, Bioland, Guangzhou, Guangdong, China
Xiaobing Zhai
State Key Laboratory of Respiratory Disease and National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China
Deyi Huang
State Key Laboratory of Respiratory Disease and National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China
Kaiwen Zhou
State Key Laboratory of Respiratory Disease and National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China
Xinyue Liang
State Key Laboratory of Respiratory Disease and National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China
Zhongfang Wang
State Key Laboratory of Respiratory Disease and National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China
ABSTRACT Limited knowledge is available on the differences in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specific antibody breadth and T cell differentiation among different COVID-19 sequential vaccination strategies. In this study, we compared the immunogenicity of the third different dose of COVID-19 vaccines, such as mRNA (I-I-M), adenoviral vector (I-I-A), and recombinant protein (I-I-R) vaccines, in terms of the magnitude and breadth of antibody response and differentiation of SARS-CoV-2-specific T and B cells. These studies were performed in the same clinical trial, and the samples were assessed in the same laboratory. IGHV1-69, IGHV3-9, and IGHV4-34 were the dominant B cell receptor (BCR) usages of the I-I-M, I-I-A, and I-I-R groups, respectively; the RBD+ B cell activation capacities were comparable. Additionally, the I-I-R group was characterized by higher numbers of regulatory T cells, circulating T follicular helper cells (cTFH) – cTFH1 (CXRC3+CCR6-), cTFH1-17 (CXRC3+CCR6+), cTFH17 (CXRC3-CCR6+), and cTFH-CM (CD45RA-CCR7+), and lower SMNE+ T cell proliferative capacity than the other two groups, whereas I-I-A showed a higher proportion and number of virus-specific CD4+ T cells than I-I-R, as determined in ex vivo experiments. Our data confirmed different SARS-CoV-2-specific antibody profiles among the three different vaccination strategies and also provided insights regarding BCR usage and T/B cell activation and differentiation, which will guide a better selection of vaccination strategies in the future.IMPORTANCEUsing the same laboratory test to avoid unnecessary interference due to cohort ethnicity, and experimental and statistical errors, we have compared the T/B cell immune response in the same cohort sequential vaccinated by different types of COVID-19 vaccine. We found that different sequential vaccinations can induce different dominant BCR usage with no significant neutralizing titers and RBD+ B-cell phenotype. Recombinant protein vaccine can induce higher numbers of regulatory T cells, circulating TFH (CTFH)1, CTFH17, and CTFH-CM, and lower SMNE+ T-cell proliferative capacity than the other two groups, whereas I-I-A showed higher proportion and number of virus-specific CD4+ T cells than I-I-R. Overall, our study provides a deep insight about the source of differences in immune protection of different types of COVID-19 vaccines, which further improves our understanding of the mechanisms underlying the immune response to SARS-CoV-2.
