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高剂量流感疫苗对老年人先天免疫的增强作用。

Boosting effect of high-dose influenza vaccination on innate immunity among elderly.

作者信息

Bonduelle Olivia, Delory Tristan, Franco-Moscardini Isabelle, Ghidi Marion, Bennacer Selma, Wokam Michele, Lenormand Mathieu, Petrier Melissa, Rogeaux Olivier, de Bernard Simon, Alves Karine, Nourikyan Julien, Lina Bruno, Combadiere Behazine, Janssen Cécile

机构信息

Sorbonne Université, Institut National de Santé et de Recherche Médicale, Inserm U1135, Centre d'Immunologie et des Maladies Infectieuses, Cimi-Paris, Paris, France.

Centre Hospitalier Annecy Genevois, Epagny Metz-Tessy, France.

出版信息

JCI Insight. 2025 Mar 4;10(8). doi: 10.1172/jci.insight.184128. eCollection 2025 Apr 22.

DOI:10.1172/jci.insight.184128
PMID:40036077
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12016920/
Abstract

BACKGROUNDThe high-dose quadrivalent influenza vaccine (QIV-HD) showed superior efficacy against laboratory-confirmed illness compared with the standard-dose quadrivalent influenza vaccine (QIV-SD) in randomized controlled trials with the elderly. However, specific underlying mechanism remains unclear.METHODSThis phase IV randomized controlled trial compared early innate responses induced by QIV-HD and QIV-SD in 59 individuals aged > 65 years. Systemic innate cells and gene signatures at day 0 (D0) and D1 as well as hemagglutinin inhibition antibody (HIA) titers at D0 and D21 after vaccination were assessed.RESULTSQIV-HD elicited robust humoral response with significantly higher antibody titers and seroconversion rates than QIV-SD. At D1 after vaccination, QIV-HD recipients showed significant reduction in innate cells, including conventional DCs and NK cells, compared with QIV-SD, correlating with significantly increased HIA titers at D21. Blood transcriptomic analysis revealed greater amplitude of gene expression in the QIV-HD arm, encompassing genes related to innate immune response, IFNs, and antigen processing and presentation, and correlated with humoral responses. Interestingly, comparative analysis with a literature dataset from young adults vaccinated with influenza standard-dose vaccine highlighted strong similarities in gene expression patterns and biological pathways with the elderly vaccinated with QIV-HD.CONCLUSIONQIV-HD induces higher HIA titers than QIV-SD, a youthful boost of the innate gene expression significantly associated with high HIA titers.TRIAL REGISTRATIONEudraCT no. 2021-004573-32.

摘要

背景

在针对老年人的随机对照试验中，高剂量四价流感疫苗（QIV-HD）相较于标准剂量四价流感疫苗（QIV-SD），对实验室确诊疾病显示出更高的疗效。然而，具体的潜在机制仍不清楚。

方法

这项IV期随机对照试验比较了QIV-HD和QIV-SD在59名年龄大于65岁的个体中诱导的早期先天免疫反应。评估了接种疫苗后第0天（D0）和第1天的全身先天免疫细胞和基因特征，以及第0天和第21天的血凝素抑制抗体（HIA）滴度。

结果

QIV-HD引发了强烈的体液免疫反应，抗体滴度和血清转化率显著高于QIV-SD。接种疫苗后第1天，与QIV-SD相比，QIV-HD接种者的先天免疫细胞，包括传统树突状细胞和自然杀伤细胞显著减少，这与第21天HIA滴度的显著增加相关。血液转录组分析显示，QIV-HD组的基因表达幅度更大，包括与先天免疫反应、干扰素以及抗原加工和呈递相关的基因，并且与体液免疫反应相关。有趣的是，与接种流感标准剂量疫苗的年轻人的文献数据集进行的比较分析突出了基因表达模式和生物学途径与接种QIV-HD的老年人的强烈相似性。

结论

QIV-HD诱导的HIA滴度高于QIV-SD，先天基因表达的年轻化增强与高HIA滴度显著相关。

试验注册

欧洲临床试验注册号

2021-004573-32。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77ff/12016920/e8038e24e61a/jciinsight-10-184128-g267.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77ff/12016920/7aa5a0bf1b1a/jciinsight-10-184128-g263.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77ff/12016920/ce28d285b243/jciinsight-10-184128-g266.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77ff/12016920/e8038e24e61a/jciinsight-10-184128-g267.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77ff/12016920/7aa5a0bf1b1a/jciinsight-10-184128-g263.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77ff/12016920/ebe6d80aa7de/jciinsight-10-184128-g264.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77ff/12016920/a58e918aa3c9/jciinsight-10-184128-g265.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77ff/12016920/ce28d285b243/jciinsight-10-184128-g266.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77ff/12016920/e8038e24e61a/jciinsight-10-184128-g267.jpg

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