接种卡介苗可诱导 50 岁以上成年人形成训练有素的先天免疫表型：几内亚比绍的随机试验

IF 4.5 3区医学 Q2 IMMUNOLOGY

Vaccine Pub Date : 2024-10-17 DOI:10.1016/j.vaccine.2024.126439

Mike Leonardus Theodorus Berendsen , Pauli Bles , Louise Charlotte Johanna de Bree , Kristoffer Jarlov Jensen , Clara Clipet Jensen , Christian Wejse , Delfim Vicente Mendes , Mihai Gheorghe Netea , Christine Stabell Benn

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引用次数: 0

摘要

背景在随机试验中对卡介苗（Bacillus Calmette-Guérin，BCG）作为非霉菌感染干预措施的有益效果进行了广泛研究。这些非特异性效果与先天性免疫细胞产生的促炎细胞因子的异源性增加有关。在几内亚比绍进行的一项单盲试验中，40 名 50 岁以上的成年人按 1:1 的比例被随机分组，皮内注射日本卡介苗（干预）或溶剂（安慰剂）。通过酶联免疫吸附试验测定了结核分枝杆菌和异源病原体刺激的外周血单核细胞上清液中白细胞介素（IL）-1β、IL-6、IL-10、干扰素（IFN）-γ和肿瘤坏死因子（TNF）-α的分泌情况。该试验已在 clinicaltrials.gov （NCT02953327）上注册。研究结果2017年1月25日至3月7日期间，40人被随机分配。接种卡介苗两个月后，日本卡介苗接种者（n = 11）对结核杆菌刺激产生的 IFN-γ 更高（几何值）。与对照组（n = 13）相比，日本卡介苗接种者（n = 11）在结核杆菌刺激下产生的 IFN-γ 更高（几何平均比（GMR）：3-91 [95 % 置信区间（CI），1-53-9-96]），在非特异性刺激下释放的促炎性先天性细胞因子 IL-1β、IL-6 和 TNF-α 更高（GMR TNF-α：1-47 [95 % CI，0-98-2-19]）。在基线定量因子呈阳性的人群中，特异性和非特异性反应都更为明显。这些效果在以前接触过结核杆菌的人群中尤为明显。未来需要进行随机试验，以确定卡介苗在保护老年人免受感染导致的发病率和死亡率方面的潜力。

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Bacillus Calmette-Guérin vaccination induces a trained innate immunity phenotype in adults over 50 years of age: A randomized trial in Guinea-Bissau

Background

The beneficial effects of Bacillus Calmette-Guérin (BCG) as an intervention against non-mycobacterial infections have been extensively studied in randomized trials. These non-specific effects have been linked to a heterologous increase of pro-inflammatory cytokine production by innate immune cells. It is unknown if BCG induces such responses in older individuals from TB-endemic countries.

Methods

In a single-blinded trial in Guinea-Bissau, 40 adults over 50 years of age were randomized 1:1 in a block of 40 to intradermal injection of BCG-Japan (intervention) or solvent (placebo). Production of interleukin (IL)-1β, IL-6, IL-10, interferon (IFN)-γ and tumor necrosis factor (TNF)-α was measured by ELISA in supernatant of peripheral blood mononuclear cells stimulated with Mycobacterium tuberculosis and heterologous pathogens. The trial was registered at clinicaltrials.gov (NCT02953327).

Findings

Between January 25 and March 7, 2017, 40 individuals were randomized. Two months after vaccination, BCG-Japan recipients (n = 11) had higher production of IFN-γ to M. tuberculosis stimulation (Geometric mean ratio (GMR): 3·91 [95 % Confidence Interval (CI), 1·53–9·96]) and increased release of the pro-inflammatory innate cytokines IL-1β, IL-6 and TNF-α to non-specific stimuli (GMR TNF-α: 1·47 [95 % CI, 0·98–2·19]) than their controls (n = 13). Both the specific and non-specific responses were more pronounced among those with a positive QuantiFERON at baseline.

Interpretation

BCG-Japan can induce a trained immunity phenotype in older adults. These effects were particularly strong in previously M. tuberculosis exposed individuals. Future randomized trials are needed to determine BCG's potential to protect the older populations from infections-driven morbidity and mortality.

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来源期刊

Vaccine 医学-免疫学

CiteScore

8.70

自引率

5.50%

发文量

992

审稿时长

131 days

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