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mBio . Diverse BCR usage and T cell activation induced by different COVID-19 sequential vaccinations

tetano

Editor, Senior Moderator
mBio


. 2024 Sep 9:e0142924.
doi: 10.1128/mbio.01429-24. Online ahead of print. Diverse BCR usage and T cell activation induced by different COVID-19 sequential vaccinations

Junxiang Wang[SUP] #[/SUP][SUP] 1 [/SUP], Kaiyi Li[SUP] #[/SUP][SUP] 1 [/SUP], Yuan Wang[SUP] #[/SUP][SUP] 1 [/SUP], Zhengfang Lin[SUP] #[/SUP][SUP] 1 2 [/SUP], Weidong Li[SUP] 1 [/SUP], Jinpeng Cao[SUP] 1 3 [/SUP], Xinyue Mei[SUP] 1 [/SUP], Rui Wei[SUP] 1 4 [/SUP], Jinglu Yang[SUP] 3 [/SUP], Xiaobing Zhai[SUP] 1 [/SUP], Deyi Huang[SUP] 1 [/SUP], Kaiwen Zhou[SUP] 1 [/SUP], Xinyue Liang[SUP] 1 [/SUP], Zhongfang Wang[SUP] 1 3 5 [/SUP]



Affiliations
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[SUP]+[/SUP] 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[SUP]+[/SUP]CCR6[SUP]-[/SUP]), cTFH1-17 (CXRC3[SUP]+[/SUP]CCR6[SUP]+[/SUP]), cTFH17 (CXRC3[SUP]-[/SUP]CCR6[SUP]+[/SUP]), and cTFH-CM (CD45RA[SUP]-[/SUP]CCR7[SUP]+[/SUP]), and lower SMNE[SUP]+[/SUP] T cell proliferative capacity than the other two groups, whereas I-I-A showed a higher proportion and number of virus-specific CD4[SUP]+[/SUP] 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.
Importance: Using 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[SUP]+[/SUP] 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[SUP]+[/SUP] T-cell proliferative capacity than the other two groups, whereas I-I-A showed higher proportion and number of virus-specific CD4[SUP]+[/SUP] 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.

Keywords: BCR usage; SARS-CoV-2; T cells; vaccine.

 
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