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接种含铝佐剂的灭活全病毒 SARS-CoV-2 疫苗后人类记忆 T 细胞的动态变化。

Human memory T cell dynamics after aluminum-adjuvanted inactivated whole-virion SARS-CoV-2 vaccination.

机构信息

Department of Basic Oncology, Hacettepe University Cancer Institute, 06100, Sihhiye, Ankara, Turkey.

Department of Internal Medicine, Faculty of Medicine, Hacettepe University, Ankara, Turkey.

出版信息

Sci Rep. 2023 Mar 21;13(1):4610. doi: 10.1038/s41598-023-31347-8.

DOI:10.1038/s41598-023-31347-8
PMID:36944716
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10028771/
Abstract

This study evaluates the functional capacity of CD4 and CD8 terminally-differentiated effector (T), central memory (T), and effector memory (T) cells obtained from the volunteers vaccinated with an aluminum-adjuvanted inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac). The volunteers were followed for T cell immune responses following the termination of a randomized phase III clinical trial. Seven days and four months after the second dose of the vaccine, the memory T cell subsets were collected and stimulated by autologous monocyte-derived dendritic cells (mDCs) loaded with SARS-CoV-2 spike glycoprotein S1. Compared to the placebo group, memory T cells from the vaccinated individuals significantly proliferated in response to S1-loaded mDCs. CD4 and CD8 memory T cell proliferation was detected in 86% and 78% of the vaccinated individuals, respectively. More than 73% (after a short-term) and 62% (after an intermediate-term) of the vaccinated individuals harbored T and/or T cells that responded to S1-loaded mDCs by secreting IFN-γ. The expression of CD25, CD38, 4-1BB, PD-1, and CD107a indicated a modulation in the memory T cell subsets. Especially on day 120, PD-1 was upregulated on CD4 T and T, and on CD8 T and T cells; accordingly, proliferation and IFN-γ secretion capacities tended to decline after 4 months. In conclusion, the combination of inactivated whole-virion particles with aluminum adjuvants possesses capacities to induce functional T cell responses.

摘要

本研究评估了志愿者接种含铝佐剂的全病毒灭活 SARS-CoV-2 疫苗(科兴疫苗)后获得的 CD4 和 CD8 终末分化效应(T)、中央记忆(T)和效应记忆(T)细胞的功能能力。志愿者在一项随机 III 期临床试验结束后随访 T 细胞免疫反应。在接种疫苗第二剂后 7 天和 4 个月,收集记忆 T 细胞亚群,并通过自体单核细胞衍生树突状细胞(mDC)刺激,mDC 负载 SARS-CoV-2 刺突糖蛋白 S1。与安慰剂组相比,接种疫苗的个体的记忆 T 细胞对 S1 负载的 mDC 显著增殖。在接种疫苗的个体中分别检测到 CD4 和 CD8 记忆 T 细胞增殖,比例分别为 86%和 78%。接种疫苗的个体中有超过 73%(短期)和 62%(中期)的个体携带 T 和/或 T 细胞,这些细胞通过分泌 IFN-γ对 S1 负载的 mDC 作出反应。CD25、CD38、4-1BB、PD-1 和 CD107a 的表达表明记忆 T 细胞亚群发生了调节。特别是在第 120 天,CD4 T 和 T 以及 CD8 T 和 T 细胞上的 PD-1 上调;相应地,增殖和 IFN-γ 分泌能力在 4 个月后趋于下降。总之,全病毒颗粒与铝佐剂的结合具有诱导功能性 T 细胞反应的能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c53/10030639/b9de2672cc7b/41598_2023_31347_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c53/10030639/8cf50e004535/41598_2023_31347_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c53/10030639/b9de2672cc7b/41598_2023_31347_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c53/10030639/8cf50e004535/41598_2023_31347_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c53/10030639/b9de2672cc7b/41598_2023_31347_Fig2_HTML.jpg

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