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.
Department of Clinical Laboratory, Dongguan Maternal and Child Health Care Hospital, Dongguan, China.
mBio. 2024 Oct 16;15(10):e0142924. doi: 10.1128/mbio.01429-24. Epub 2024 Sep 9.
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 (CXRC3CCR6), cTFH1-17 (CXRC3CCR6), cTFH17 (CXRC3CCR6), and cTFH-CM (CD45RACCR7), 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.
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 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.
关于不同 COVID-19 序贯接种策略中严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）特异性抗体广度和 T 细胞分化的差异，目前知识有限。在这项研究中，我们比较了信使 RNA（I-I-M）、腺病毒载体（I-I-A）和重组蛋白（I-I-R）疫苗的第三剂不同 COVID-19 疫苗的免疫原性，从 SARS-CoV-2 特异性 T 和 B 细胞的抗体反应和分化的幅度和广度方面进行比较。这些研究在同一临床试验中进行，并且在同一实验室中评估了样本。IGHV1-69、IGHV3-9 和 IGHV4-34 分别是 I-I-M、I-I-A 和 I-I-R 组的主导 B 细胞受体（BCR）使用情况；RBD B 细胞激活能力相当。此外，与其他两组相比，I-I-R 组的调节性 T 细胞、循环滤泡辅助 T 细胞（cTFH）-cTFH1（CXRC3CCR6）、cTFH1-17（CXRC3CCR6）、cTFH17（CXRC3CCR6）和 cTFH-CM（CD45RACCR7）数量较多，而 SMNE T 细胞增殖能力较低，而 I-I-A 组在体外实验中表现出比 I-I-R 组更高比例和数量的病毒特异性 CD4 T 细胞。我们的数据证实了三种不同接种策略之间 SARS-CoV-2 特异性抗体谱的差异，并提供了有关 BCR 使用情况以及 T/B 细胞激活和分化的见解，这将有助于未来更好地选择接种策略。
使用相同的实验室检测方法，避免由于队列种族、实验和统计误差而导致的不必要干扰，我们比较了同一队列中不同类型 COVID-19 疫苗序贯接种的 T/B 细胞免疫反应。我们发现，不同的序贯接种可诱导不同的主导 BCR 使用，而中和滴度和 RBD B 细胞表型无显著差异。与其他两组相比，重组蛋白疫苗可诱导更多的调节性 T 细胞、循环 TFH（CTFH）1、CTFH17 和 CTFH-CM，以及更低的 SMNE T 细胞增殖能力，而 I-I-A 组比 I-I-R 组显示出更高比例和数量的病毒特异性 CD4 T 细胞。总体而言，我们的研究深入了解了不同类型 COVID-19 疫苗免疫保护差异的来源，进一步加深了我们对 SARS-CoV-2 免疫反应机制的理解。
