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在乌干达农村地区,蠕虫引发的肠道炎症和微生物易位与疫苗反应改变有关。

Helminth driven gut inflammation and microbial translocation associate with altered vaccine responses in rural Uganda.

作者信息

Nassuuna Jacent, Sterk Joas, Walusimbi Bridgious, Natukunda Agnes, Nkangi Ronald, Amongin Rebecca, Zirimenya Ludoviko, Webb Emily L, Elliott Alison M, Nkurunungi Gyaviira

机构信息

Immunomodulation and Vaccines Focus Area, Vaccine Research Theme, MRC/UVRI and LSHTM Uganda Research Unit, Entebbe, Uganda.

University of Glasgow, Glasgow, UK.

出版信息

NPJ Vaccines. 2025 Mar 26;10(1):56. doi: 10.1038/s41541-025-01116-x.

DOI:10.1038/s41541-025-01116-x
PMID:40140378
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11947158/
Abstract

Vaccine responses are sometimes impaired in rural, low-income settings. Helminth-associated gut barrier dysfunction and microbial translocation (MT) may be implicated. We used samples from a trial of praziquantel treatment-effects on vaccine responses in Schistosoma mansoni (Sm)-endemic Ugandan islands, measuring intestinal fatty acid-binding protein 2 (I-FABP2), lipopolysaccharide-binding protein, anti-endotoxin core antibodies (EndoCab), soluble CD14 (sCD14) in plasma, and faecal lipocalin-2, occult blood (FOB), and calprotectin (fCAL), and evaluating their associations with baseline helminth infection, praziquantel treatment, and responses to BCG, yellow fever, typhoid, HPV, and tetanus-diphtheria vaccines. Sm associated positively with fCAL and FOB, hookworm with I-FABP2, and any helminth with EndoCab IgM, fCAL and FOB. Sm associated inversely with sCD14. Praziquantel treatment reduced all marker concentrations, significantly fCAL and FOB, implying that Sm-associated gut inflammation and MT is reversible. Associations of assessed markers with vaccine-specific responses were predominantly inverse. Interventions to improve gut barrier function may enhance vaccine responsiveness.

摘要

在农村低收入地区,疫苗反应有时会受到损害。与蠕虫相关的肠道屏障功能障碍和微生物易位(MT)可能与之有关。我们使用了来自一项关于吡喹酮对曼氏血吸虫(Sm)流行的乌干达岛屿疫苗反应治疗效果试验的样本,测量血浆中的肠脂肪酸结合蛋白2(I-FABP2)、脂多糖结合蛋白、抗内毒素核心抗体(EndoCab)、可溶性CD14(sCD14),以及粪便中的脂质运载蛋白2、潜血(FOB)和钙卫蛋白(fCAL),并评估它们与基线蠕虫感染、吡喹酮治疗以及对卡介苗、黄热病、伤寒、人乳头瘤病毒和破伤风-白喉疫苗反应之间的关联。Sm与fCAL和FOB呈正相关,钩虫与I-FABP2呈正相关,任何蠕虫与EndoCab IgM、fCAL和FOB呈正相关。Sm与sCD14呈负相关。吡喹酮治疗降低了所有标志物的浓度,显著降低了fCAL和FOB,这意味着与Sm相关的肠道炎症和MT是可逆的。评估的标志物与疫苗特异性反应的关联主要呈负相关。改善肠道屏障功能的干预措施可能会增强疫苗反应性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b11/11947158/bf5643b28f89/41541_2025_1116_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b11/11947158/4feae34c8869/41541_2025_1116_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b11/11947158/fc63890c062e/41541_2025_1116_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b11/11947158/bf5643b28f89/41541_2025_1116_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b11/11947158/4feae34c8869/41541_2025_1116_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b11/11947158/54b382c42c36/41541_2025_1116_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b11/11947158/2fdcb6a281f3/41541_2025_1116_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b11/11947158/fc63890c062e/41541_2025_1116_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b11/11947158/bf5643b28f89/41541_2025_1116_Fig5_HTML.jpg

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本文引用的文献

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Lancet Glob Health. 2024 Nov;12(11):e1860-e1870. doi: 10.1016/S2214-109X(24)00340-1.
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The effect of intensive praziquantel administration on vaccine-specific responses among schoolchildren in Ugandan schistosomiasis-endemic islands (POPVAC A): an open-label, randomised controlled trial.密集型吡喹酮给药对乌干达血吸虫病流行岛屿(POPVAC A)学龄儿童疫苗特异性反应的影响:一项开放标签、随机对照试验。
Lancet Glob Health. 2024 Nov;12(11):e1826-e1837. doi: 10.1016/S2214-109X(24)00280-8.
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