Using ATAC-Seq to investigate the impact of vaccination on the epigenome

We used a mouse model to investigate whether live (BCG) and non-live (DTPw) vaccines differentially reprogram trained immune responses and to investigate whether immunisation with DTPw altered susceptibility to sepsis. We found that compared to BCG-immunised mice, DTPw immunisation led to altered monocyte and dendritic cell (DC) cytokine responses to subsequent secondary stimuli, as well as genome-wide changes to chromatin accessibility in DCs. These effects were evident months after immunisation and are consistent with different programs of trained immunity being induced by live versus non-live vaccines. There are 12 samples total from 12 individual mice at one timepoint. 5 with each vaccine (BCG and DTPw) and 2 not vaccinated which are referred to as mock. Dendritic cells from these were subjected to ATAC-Seq.

本研究借助小鼠模型，旨在探究活疫苗卡介苗（BCG）与非活疫苗全细胞百白破联合疫苗（DTPw）能否差异化重编程训练免疫应答，同时考察DTPw免疫是否会改变小鼠对脓毒症的易感性。研究结果显示，与卡介苗免疫小鼠相比，全细胞百白破联合疫苗免疫可改变单核细胞与树突状细胞（DC）对后续二次刺激的细胞因子应答模式，同时可诱导树突状细胞内全基因组范围的染色质开放性改变。此类效应在免疫接种数月后仍可被观测到，与活疫苗与非活疫苗诱导不同训练免疫程序的推论一致。本研究共纳入12只个体小鼠在单一时间点采集的12份样本：其中接种卡介苗与全细胞百白破联合疫苗的小鼠各5只，剩余2只未接种疫苗，作为空白对照（mock）。提取上述样本中的树突状细胞进行转座酶可及性测序（ATAC-Seq）。