基线外周血液批量转录组学对老年人流感疫苗反应的有限预测效用
Thomas Boissiere-O'Neill1,2, Sriganesh Srihari1, Laurence Macia1
1Global Clinical Development, Sanofi, Woolloongabba, Brisbane, QLD 4102, Australia.
Vaccines
|January 28, 2026
概括
研究老年人的基因表达发现,预测流感疫苗反应的能力有限. 转录组签名无法可靠地识别非响应者,这表明需要进一步研究先进的方法.
科学领域:
- 免疫学 免疫学 免疫学
- 基因组学就是基因组学.
- 老年学是一门学科.
背景情况:
- 老年人表现出免疫功能减弱 (免疫性),导致流感疫苗响应能力降低和感染风险增加.
- 目前的疫苗接种策略缺乏生物标志物来识别不太可能对标准疫苗做出反应的老年人,这阻碍了个性化的方法.
- 识别不响应者对于优化疫苗策略至关重要,例如高剂量或辅助剂配方.
研究的目的:
- 为了确定外围血液单核细胞中基线转录组签名,预测65岁及以上个体的流感疫苗反应.
- 在独立的发现和验证队伍中评估这些签名的预测性能.
主要方法:
- 对来自老年人 (≥65岁) 外围血液单核细胞的大量RNA测序数据的分析.
- 根据三个流感疫苗成分的血液凝结抑制试验标位,将个人分为三重响应者 (TR) 或三重不响应者 (TNR).
- 基因表达衍生反应评分的开发和验证.
主要成果:
- 总共有1152个差异表达的基因在基线时在TRs和TNRs之间被确定.
- TRs显示在B细胞激活和蛋白质合成途径中的丰富,而TNRs在先天免疫和血小板激活途径中的丰富.
- 基因表达衍生响应得分在发现队列中显示出高准确度 (AUC = 0.98),但在验证队列中显示出明显较低的准确度 (AUC = 0.69),不超过临床预测因素.
结论:
- 基线转录组特征提供了对老年人疫苗反应的机械洞察力,但对识别非响应者具有有限的预测价值.
- 进一步的研究应该探索更高分辨率或细胞特异的方法,如单细胞RNA测序或流细胞计,以改善预测.
- 目前的转录组签名不能可靠地预测老年人流感疫苗反应,这表明需要更先进的方法.
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