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养老院居民中初次接种和加强接种 SARS-CoV-2 信使 RNA 疫苗后的 T 细胞介导的反应。

T-Cell Mediated Response after Primary and Booster SARS-CoV-2 Messenger RNA Vaccination in Nursing Home Residents.

机构信息

Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy.

Department of Cardiovascular, Endocrine-Metabolic Diseases and Aging, Istituto Superiore di Sanità, Rome, Italy.

出版信息

J Am Med Dir Assoc. 2023 Feb;24(2):140-147.e2. doi: 10.1016/j.jamda.2022.11.024. Epub 2022 Dec 7.

Abstract

OBJECTIVES

Nursing home (NH) residents have been significantly affected by the coronavirus disease 2019 (COVID-19) pandemic. Studies addressing the immune responses induced by COVID-19 vaccines in NH residents have documented a good postvaccination antibody response and the beneficial effect of a third booster vaccine dose. Less is known about vaccine-induced activation of cell-mediated immune response in frail older individuals in the long term. The aim of the present study is to monitor messenger RNA SARS-CoV-2 vaccine-induced T-cell responses in a sample of Italian NH residents who received primary vaccine series and a third booster dose and to assess the interaction between T-cell responses and humoral immunity.

DESIGN

Longitudinal cohort study.

SETTING AND PARTICIPANTS

Thirty-four residents vaccinated with BNT162b2 messenger RNA SARS-CoV-2 vaccine between February and April 2021 and who received a third BNT162b2 booster dose between October and November 2021 were assessed for vaccine-induced immunity 6 (prebooster) and 12 (postbooster) months after the first BNT162b2 vaccine dose.

METHODS

Pre- and postbooster cell-mediated immunity was assessed by intracellular cytokine staining of peripheral blood mononuclear cells stimulated in vitro with peptides covering the immunodominant sequence of SARS-CoV-2 spike protein. The simultaneous production of interferon-γ, tumor necrosis factor-α, and interleukin-2 was measured. Humoral immunity was assessed in parallel by measuring serum concentration of antitrimeric spike IgG antibodies.

RESULTS

Before the booster vaccination, 31 out of 34 NH residents had a positive cell-mediated immunity response to spike. Postbooster, 28 out of 34 had a positive response. Residents without a previous history of SARS-CoV-2 infection, who had a lower response prior the booster administration, showed a greater increase of T-cell responses after the vaccine booster dose. Humoral and cell-mediated immunity were, in part, correlated but only before booster vaccine administration.

CONCLUSIONS AND IMPLICATIONS

The administration of the booster vaccine dose restored spike-specific T-cell responses in SARS-CoV-2 naïve residents who responded poorly to the first immunization, while a previous SARS-CoV-2 infection had an impact on the magnitude of vaccine-induced cell-mediated immunity at earlier time points. Our findings imply the need for a continuous monitoring of the immune status of frail NH residents to adapt future SARS-CoV-2 vaccination strategies.

摘要

目的

养老院(NH)居民受到 2019 年冠状病毒病(COVID-19)大流行的严重影响。研究表明,COVID-19 疫苗在 NH 居民中诱导的免疫反应良好,并且第三剂加强疫苗剂量有益。关于脆弱的老年人长期内疫苗诱导的细胞介导免疫反应知之甚少。本研究的目的是监测接受初级疫苗系列和第三剂加强剂的意大利 NH 居民中 SARS-CoV-2 疫苗诱导的 T 细胞反应,并评估 T 细胞反应与体液免疫之间的相互作用。

设计

纵向队列研究。

地点和参与者

34 名居民于 2021 年 2 月至 4 月期间接种 BNT162b2 信使 RNA SARS-CoV-2 疫苗,并于 2021 年 10 月至 11 月期间接种第三剂 BNT162b2 加强剂,在第一次 BNT162b2 疫苗接种后 6 个月(预加强)和 12 个月(后加强)评估疫苗诱导的免疫力。

方法

通过体外用涵盖 SARS-CoV-2 刺突蛋白免疫显性序列的肽刺激外周血单核细胞来评估预加强和后加强的细胞介导免疫。同时测量干扰素-γ、肿瘤坏死因子-α 和白细胞介素-2 的产生。同时平行评估血清中抗三聚体刺突 IgG 抗体的浓度。

结果

在加强疫苗接种之前,34 名 NH 居民中有 31 名对刺突有阳性细胞介导免疫反应。加强后,34 名中有 28 名有阳性反应。没有 SARS-CoV-2 感染史的居民,在加强前的反应较低,在加强疫苗剂量后,T 细胞反应增加更大。体液免疫和细胞免疫部分相关,但仅在加强疫苗接种前相关。

结论和意义

加强疫苗接种剂量恢复了对初次免疫反应不佳的 SARS-CoV-2 未感染者的刺突特异性 T 细胞反应,而先前的 SARS-CoV-2 感染对早期时间点疫苗诱导的细胞介导免疫反应的幅度有影响。我们的发现意味着需要持续监测脆弱的 NH 居民的免疫状况,以调整未来的 SARS-CoV-2 疫苗接种策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a260/9726683/7a2fa5b713c1/gr1_lrg.jpg

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