Division of Basic and Clinical Immunology, University of California Irvine, Irvine, California, USA.
Int Arch Allergy Immunol. 2022;183(3):350-359. doi: 10.1159/000520046. Epub 2021 Nov 18.
In the trials of corona virus vaccines, detailed analyses of subsets of lymphocytes were not carried out. We present perhaps the most comprehensive immunological analysis of 29 subsets of B and T cells in 2 healthy subjects receiving 2 doses of the Pfizer SARS-CoV-2 (COVID-19) vaccine.
Analyses were performed prior to vaccination, 3 weeks following the 1st dose, and 4 weeks following the 2nd dose. Total, naïve (TN), and different memory and effector subsets (TCM, TEM, and TEMRA) of CD4+ and CD8+ T cells; SARS-CoV-2 spike protein-specific tetramer+, and cytotoxic CD8+ T; subsets of T follicular cells (TFH, TFH1, TFH2, TFH1/TFH17, and TFH17); B-cell subsets (mature B cells, naive B cells, transitional B cells, marginal zone B cells, class-switched memory B cells, germinal center B cells, and CD21low B cells), and plasmablasts; and regulatory lymphocytes (CD4+ Treg, CD8+ Treg, Breg, and TFR cells) were evaluated with specific monoclonal antibodies by flow cytometry.
A lack of COVID-19 IgG antibodies after the 1st dose in one of 2 subjects was associated with increased regulatory lymphocytes and decreased plasmablasts. Seroconversion after the 2nd dose in this subject was associated with decreased TFR cells and increased plasmablasts. In both subjects, CD4 TEM and CD8 TCM were markedly increased following the 2nd dose. TFH1 and regulatory lymphocytes were increased (except Breg) following the 1st dose. A striking increase in SARS-CoV-2-specific CD8+ T cells was observed following the 2nd dose.
Our data support the need for 2nd dose of vaccine to induce strong SARS-CoV-2 CD8 T-cell specific response and generation of memory subsets of CD4+ and CD8+ T cells. Regulatory lymphocytes appear to play a role in the magnitude of response.
在冠状病毒疫苗的试验中,并未对淋巴细胞亚群进行详细分析。我们展示了 2 名健康受试者在接种 2 剂辉瑞 SARS-CoV-2(COVID-19)疫苗后,对 29 种 B 和 T 细胞亚群进行的或许是最全面的免疫分析。
在接种疫苗之前、第 1 剂后 3 周和第 2 剂后 4 周进行分析。分析了 CD4+和 CD8+T 细胞的总、幼稚(TN)和不同记忆和效应亚群(TCM、TEM 和 TEMRA);SARS-CoV-2 刺突蛋白特异性四聚体+和细胞毒性 CD8+T;滤泡辅助 T 细胞(TFH、TFH1、TFH2、TFH1/TFH17 和 TFH17)亚群;B 细胞亚群(成熟 B 细胞、幼稚 B 细胞、过渡 B 细胞、边缘区 B 细胞、类别转换记忆 B 细胞、生发中心 B 细胞和 CD21low B 细胞)和浆母细胞;以及调节性淋巴细胞(CD4+Treg、CD8+Treg、Breg 和 TFR 细胞),并通过流式细胞术使用特异性单克隆抗体进行评估。
2 名受试者中的 1 名在第 1 剂后缺乏 COVID-19 IgG 抗体,与调节性淋巴细胞增加和浆母细胞减少有关。该受试者在第 2 剂后发生血清转化,与 TFR 细胞减少和浆母细胞增加有关。在两名受试者中,第 2 剂后 CD4 TEM 和 CD8 TCM 明显增加。第 1 剂后 TFH1 和调节性淋巴细胞增加(Breg 除外)。第 2 剂后观察到 SARS-CoV-2 特异性 CD8+T 细胞显著增加。
我们的数据支持需要接种第 2 剂疫苗来诱导强烈的 SARS-CoV-2 CD8 T 细胞特异性反应和产生 CD4+和 CD8+T 细胞的记忆亚群。调节性淋巴细胞似乎在反应强度中发挥作用。