RNA-sequencing of PBMC cultured with PolyI:C or LPS, from a pediatric cohort who received OM85 or placebo.

Bacterial-derived immune training agents are a showing promise in clinical studies for prevention of lower respiatory infections in high-risk infants but underlying mechanisms of this protective effect are unclear. To address this, we employed a systems-level analysis of transcriptional responses to immune stimuli (LPS and PolyI:C) in infants who participated in a clinical trial of one such agent called OM85 which was clinically effective. We identified key protected innate immune changes using a series of analytical approaches such as reduced inflammatory responses to LPS and enhanced antibacterial interferon responses potentially mediated through IRF7. We posit that immune training agents exemplified by OM85 potentially protect against infant severe lower respiratory infection principally via effects on innate immune responses targeting the bacterial components of the mixed respiratory viral/bacterial infections which are characteristic of this age group. Two participant groups; high-risk infants (aged 4-8 months) who received either OM85 or Placebo during their first winter of life as part of a previously published randomised controlled trial. Two timepoints; PBMC collected pre and post treatment period. Three in vitro stimulants: PBMC cultured with LPS, polyI:C or paired controls for 24 hours.

细菌来源的免疫训练剂在高危婴儿下呼吸道感染预防的临床研究中展现出应用前景，但其保护效应的潜在机制尚未阐明。为阐明该机制，本研究对参与某临床有效免疫训练剂OM85临床试验的婴儿样本，开展了针对免疫刺激物脂多糖（LPS）和聚肌胞苷酸（PolyI:C）的转录应答系统级分析。本研究通过一系列分析方法，鉴定出关键的保护性先天免疫变化：包括对LPS的炎症应答减弱，以及可能通过干扰素调节因子7（IRF7）介导的抗菌干扰素应答增强。我们提出，以OM85为代表的免疫训练剂，主要通过调控针对该年龄段典型混合呼吸道病毒-细菌感染中细菌组分的先天免疫应答，从而实现对婴儿重症下呼吸道感染的保护作用。研究共纳入两组受试者：均为4~8月龄的高危婴儿，且均处于出生后首个冬季，作为已发表的随机对照试验的一部分，分别接受OM85或安慰剂干预。共设置两个采样时间点：分别于干预前及干预后采集受试者外周血单个核细胞（PBMC）。体外设置三类刺激条件：将PBMC分别与LPS、polyI:C或对应对照共培养24小时。