The impact of physical frailty on the response to inactivated influenza vaccine in older adults. The impact of physical frailty on the response to inactivated influenza vaccine in older adults

Physical frailty's impact on hemagglutination inhibition antibody titers (HAI) and peripheral blood mononuclear cell (PBMC) transcriptional responses after influenza vaccination is unclear. Physical frailty was assessed using the 5-item Fried frailty phenotype in 168 community- and assisted-living adults ≥55 years of age during an observational study. Blood was drawn before, 3, 7, and 28 days post-vaccination with the 2017-2018 inactivated influenza vaccine. HAI response to the A/H1N1 strain was measured at Days 0 and 28 using seropositivity, seroconversion, log2 HAI titers, and fold-rise in log2 HAI titers. RNA sequencing of PBMCs from Days 0, 3 and 7 was measured in 28 participants and compared using pathway analyses. Frailty was not significantly associated with any HAI outcome in multivariable models. Compared with non-frail participants, frail participants expressed decreased cell proliferation, metabolism, antibody production, and interferon signaling genes. Conversely, frail participants showed elevated gene expression in IL-8 signaling, T-cell exhaustion, and oxidative stress pathways compared with non-frail participants. These results suggest that reduced effectiveness of influenza vaccine among older, frail individuals may be attributed to immunosenescence-related changes in PBMCs that are not reflected in antibody levels. Overall design: Transcriptomic analysis of blood cells from patients before infleunza vaccination and at days 3 and 7 post vaccination. ----------------------------------------------- Authors state "Due to privacy issues, we will not be uploading raw data because the data consists of human sequences."

体力衰弱（physical frailty）对流感疫苗接种后血凝抑制抗体滴度（hemagglutination inhibition antibody titers, HAI）以及外周血单个核细胞（peripheral blood mononuclear cell, PBMC）转录应答的影响尚不明确。本项观察性研究中，研究人员采用包含5个条目的Fried衰弱表型，对168名年龄≥55岁的社区居住及接受辅助生活照护的成年受试者的体力衰弱状况进行评估。受试者接种2017-2018年度灭活流感疫苗后，分别于接种前、接种后第3、7、28天采集外周血样本。研究于第0天和第28天，通过血清阳性率、血清转换率、log₂ HAI滴度以及log₂ HAI滴度的倍增倍数，检测受试者针对A/H1N1毒株的HAI应答水平。本研究纳入28名受试者，对其于接种前（第0天）、接种后第3、7天采集的PBMC进行RNA测序，并通过通路分析对测序结果进行比较。在多变量模型中，体力衰弱与任何HAI相关结局均无显著关联。与非衰弱受试者相比，衰弱受试者体内细胞增殖、代谢、抗体生成以及干扰素信号通路相关基因的表达水平降低。反之，与非衰弱受试者相比，衰弱受试者体内IL-8信号通路、T细胞耗竭以及氧化应激通路相关基因的表达水平升高。上述结果表明，老年衰弱个体的流感疫苗保护效力降低，可能与PBMC中与免疫衰老相关的变化有关，而这类变化无法通过抗体水平体现。研究整体设计：流感疫苗接种前及接种后第3、7天的血细胞转录组学分析。----------------------------------------------- 作者声明："由于数据包含人类序列且涉及隐私问题，我们将不会上传原始数据。"