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SARS-CoV-2 免疫调控 IFNγ 产生的 T 细胞和 NK 细胞持久性扩增。

SARS-CoV-2 Immunization Orchestrates the Amplification of IFNγ-Producing T Cell and NK Cell Persistence.

机构信息

Lab of Cardiovascular Diabetology and Dysmetabolic Disease, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) MultiMedica, Milan, Italy.

Department of Experimental Oncology, European Institute of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, Italy.

出版信息

Front Immunol. 2022 Feb 14;13:798813. doi: 10.3389/fimmu.2022.798813. eCollection 2022.

Abstract

UNLABELLED

A successful vaccination would represent the most efficient means to control the pandemic of Coronavirus Disease-19 (COVID-19) that led to millions of deaths worldwide. Novel mRNA-based vaccines confer protective immunity against SARS-CoV-2, but whether immunity is immediately effective and how long it will remain in recipients are uncertain. We sought to assess the effectiveness of a two-dose regimen since the boosts are often delayed concerning the recommended intervals.

METHODS

A longitudinal cohort of healthcare workers (HCW, = 46; 30.4% men; 69.6% women; mean age 36.05 ± 2.2 years) with no SARS-CoV-2 infection as documented by negative polymerase chain reaction was immunophenotyped in PBMC once a week for 4 weeks from the prime immunization (Pfizer mRNA BNT162b2) and had received 2 doses, to study the kinetic response.

RESULTS

We identified three risk groups to develop SARS-CoV-2 infection IgG-based (late responders, R; early responders, R; pauci responders, PR). In all receipts, amplification of B cells and NK cells, including IL4-producing B cells and IL4-producing CD8 T cells, is early stimulated by the vaccine. After the boost, we observed a growing increase of NK cells but a resistance of T cells, IFNγ-producing CD4T cells, and IFNγ-producing NK cells. Also, hematologic parameters decline until the boost. The positive association of IFNγ-producing NK with IFNγ-producing CD4T cells by the multiple mixed-effect model, adjusted for confounders (p = 0.036) as well as the correlation matrix (r = 0.6, p < 0.01), suggests a relationship between these two subsets of lymphocytes.

CONCLUSIONS

These findings introduce several concerns about policy delay in vaccination: based on immunological protection, B cells and the persistent increase of NK cells during 2 doses of the mRNA-based vaccine could provide further immune protection against the virus, while CD8 T cells increased slightly only in the R and PR groups.

摘要

未加说明

一种成功的疫苗接种将是控制导致全球数百万人死亡的 2019 年冠状病毒病(COVID-19)大流行的最有效手段。新型基于 mRNA 的疫苗可提供针对 SARS-CoV-2 的保护性免疫,但免疫是否立即有效以及在受种者中能持续多长时间尚不确定。我们试图评估两剂方案的有效性,因为加强针通常会延迟到推荐的间隔时间。

方法

一项针对医护人员(HCW)的纵向队列研究(=46;30.4%男性;69.6%女性;平均年龄 36.05±2.2 岁),这些医护人员在首次免疫(辉瑞 mRNA BNT162b2)后一周内每周在 PBMC 中免疫表型化一次,共进行 4 周,并接受了两剂疫苗,以研究动力学反应。没有 SARS-CoV-2 感染的记录,通过聚合酶链反应检测为阴性。

结果

我们确定了三种发生 SARS-CoV-2 感染 IgG 型(迟发应答者 R;早期应答者 R;寡应答者 PR)的风险组。在所有接受者中,疫苗可早期刺激 B 细胞和 NK 细胞的扩增,包括产生 IL4 的 B 细胞和产生 IL4 的 CD8 T 细胞。在加强针后,我们观察到 NK 细胞的数量不断增加,但 T 细胞、IFNγ 产生的 CD4T 细胞和 IFNγ 产生的 NK 细胞则存在抵抗。此外,血液学参数在加强针前下降。通过多元混合效应模型,对混杂因素进行调整(p=0.036),以及相关矩阵(r=0.6,p<0.01),我们发现 IFNγ 产生的 NK 细胞与 IFNγ 产生的 CD4T 细胞之间存在正相关,这提示这两种淋巴细胞亚群之间存在关系。

结论

这些发现引发了对疫苗接种政策延迟的几点关注:基于免疫保护,基于 mRNA 的疫苗的两剂接种后,B 细胞和 NK 细胞的持续增加可能会为病毒提供进一步的免疫保护,而 CD8 T 细胞仅在 R 和 PR 组中略有增加。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94ef/8882867/7294b851fb1c/fimmu-13-798813-g001.jpg

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