GSK, 1330 Rixensart, Belgium.
Bioinformatics Laboratory, University of Amsterdam, 1012 WX Amsterdam, Netherlands.
Sci Transl Med. 2020 Nov 11;12(569). doi: 10.1126/scitranslmed.aay8618.
The current routine use of adjuvants in human vaccines provides a strong incentive to increase our understanding of how adjuvants differ in their ability to stimulate innate immunity and consequently enhance vaccine immunogenicity. Here, we evaluated gene expression profiles in cells from whole blood elicited in naive subjects receiving the hepatitis B surface antigen formulated with different adjuvants. We identified a core innate gene signature emerging 1 day after the second vaccination and that was shared by the recipients of vaccines formulated with adjuvant systems AS01, AS01, or AS03. This core signature associated with the magnitude of the hepatitis B surface-specific antibody response and was characterized by positive regulation of genes associated with interferon-related responses or the innate cell compartment and by negative regulation of natural killer cell-associated genes. Analysis at the individual subject level revealed that the higher immunogenicity of AS01-adjuvanted vaccine was linked to its ability to induce this signature in most vaccinees even after the first vaccination. Therefore, our data suggest that adjuvanticity is not strictly defined by the nature of the receptors or signaling pathways it activates but by the ability of the adjuvant to consistently induce a core inflammatory signature across individuals.
目前，在人用疫苗中常规使用佐剂，这强烈激励我们增加对佐剂在刺激固有免疫以及由此增强疫苗免疫原性方面的能力差异的理解。在这里，我们评估了接受不同佐剂配方的乙型肝炎表面抗原疫苗接种的初免受试者的全血细胞中的基因表达谱。我们鉴定出在第二次接种后 1 天出现的核心固有基因特征，并且该特征与接受 AS01、AS01 或 AS03 佐剂系统配方疫苗的受试者共享。该核心特征与乙型肝炎表面特异性抗体应答的幅度相关，其特征是与干扰素相关反应或固有细胞区室相关的基因的正调节，以及与自然杀伤细胞相关基因的负调节。在个体受试者水平上的分析表明，AS01 佐剂疫苗的更高免疫原性与其在大多数疫苗接种者中诱导该特征的能力相关，甚至在第一次接种后也是如此。因此，我们的数据表明，佐剂的佐剂作用不是由其激活的受体或信号通路的性质严格定义的，而是由佐剂在个体间持续诱导核心炎症特征的能力定义的。
