Early transcriptomic responses to TB vaccine ID93 + GLA-SE (TBVPX-203)

ID93+GLA-SE is a candidate subunit vaccine that will soon be evaluated in a Phase 2b efficacy trial for prevention of recurrent TB among patients undergoing TB treatment. Though the vaccine regimen was shown to elicit robust CD4+ T cell and IgG antibody responses in a clinical trial among recently treated TB patients (TBVPX-203), the mechanisms underlying the development of these responses is not well understood. In this study we used specimens from TBVPX-203 participants to describe the changes in peripheral blood gene expression that occur after ID93+GLA-SE vaccination. Analyses revealed several distinct modules of covarying genes that were either up- or down-regulated after vaccination, including genes associated with innate immune pathways at 3 days post-vaccination and genes associated with lymphocyte expansion and B cell activation at 7 days post-vaccination. Notably, the regulation of these gene modules was affected by the dose schedule and participant sex. The results provide insight into the complex interplay of the innate and adaptive arms of the immune system in developing responses to vaccination with ID93+GLA-SE and demonstrate how dosing and schedule can affect vaccine responses.ID93+GLA-SE是一款候选亚单位疫苗（subunit vaccine），即将启动2b期有效性临床试验，用于评估其在接受结核病治疗的患者中预防复发性结核病的效果。尽管该疫苗方案在针对近期完成结核病治疗患者的临床试验（TBVPX-203）中被证实可诱导强烈的CD4阳性T细胞（CD4+ T cell）及IgG抗体（IgG antibody）应答，但此类应答的潜在产生机制尚未完全阐明。本研究借助TBVPX-203临床试验的受试者样本，解析ID93+GLA-SE接种后外周血基因表达的动态变化。分析结果显示，疫苗接种后存在多个不同的共表达基因模块，分别呈现上调或下调趋势：接种后3天的模块富集先天免疫通路相关基因，接种后7天的模块则与淋巴细胞增殖及B细胞活化（B cell activation）相关。值得注意的是，这些基因模块的调控模式受给药方案与受试者性别的共同影响。本研究结果为解析ID93+GLA-SE疫苗接种后免疫系统先天与适应性免疫分支之间的复杂相互作用提供了新视角，并阐明了给药剂量与方案如何影响疫苗应答。