The study aimed at identifying biomarkers of immune response elicited by non-adjuvanted-(NAV) and adjuvanted-(AV) H1N1(pdm09) vaccines. The results showed that despite both vaccines elicited similar levels of anti-H1N1 antibodies at day30 after vaccination, higher reactivity was observed in AV at day180. While AV induced early changes in cell-surface molecules on monocytes, CD4⁺, CD8⁺ T-cells and B-cells, NAV triggered minor changes, starting later on at day3. Furthermore, AV induced a late and persistent increase in TLR gene expression after day3, except for tlr4, while NAV displayed earlier but transient tlr3/4/7/9 up-regulation. Contrasting with NAV, prominent chemokine gene expression (cxcl8,cxcl9,ccl5) and a broad spectrum up-regulation of plasmatic biomarkers (CXCL8,IL-6,IL-1β,IL-12,IL-10) was evident in AV, which showed a major involvement of TNF and IL-10. Similarly, AV induced a robust IL-10-modulated proinflammatory storm, with early and persistent involvement of TNF-α/IL-12/IFN-γ axis derived from NK-cells, CD4⁺ and CD8⁺ T-cells along with promiscuous production of IL-4/IL-5/IL-13. Conversely, NAV promotes a concise and restricted intracytoplasmic chemokine/cytokine response, essentially mediated by TNF-α and IL-4, with late IL-10 production by CD8⁺ T-cells. Systems biology approach underscored that AV guided the formation of an imbricate network characterized by a progressive increase in the number of neighborhood connections amongst innate and adaptive immunity. In AV, the early cross-talk between innate and adaptive immunity, followed by the triad NK/CD4⁺/CD8⁺ T-cells at day3, sponsored a later/robust biomarker network. These findings indicate the relevance of adjuvanted vaccination to orchestrate broad, balanced and multifactorial cellular immune events that lead ultimately to a stronger H1N1 humoral immunity.

该研究旨在确定非佐剂 (NAV) 和佐剂 (AV) H1N1(pdm09) 疫苗引发的免疫反应的生物标志物。结果表明，尽管两种疫苗在接种后第 30 天引发了相似水平的抗 H1N1 抗体，但在第 180 天在 AV 中观察到更高的反应性。虽然 AV 诱导单核细胞、CD4 ⁺、CD8 ⁺ T 细胞和 B 细胞上细胞表面分子的早期变化，但 NAV 引发了微小的变化，从第 3 天晚些时候开始。此外，除tlr4外，AV 在第 3天后诱导了 TLR 基因表达的晚期和持续增加，而 NAV 显示较早但短暂的tlr3/4/7/9上调。与 NAV 相比，显着的趋化因子基因表达 ( cxcl8,cxcl9,ccl5）和血浆生物标志物（CXCL8、IL-6、IL-1β、IL-12、IL-10）的广谱上调在 AV 中很明显，这表明 TNF 和 IL-10 的主要参与。类似地，AV 诱导了强烈的 IL-10 调节的促炎风暴，来自 NK 细胞、CD4 ⁺和 CD8 ⁺ T 细胞的 TNF-α/IL-12/IFN-γ 轴的早期和持续参与以及混杂的产生IL-4/IL-5/IL-13。相反，NAV 促进简洁且受限的胞质内趋化因子/细胞因子反应，主要由 TNF-α 和 IL-4 介导，晚期 IL-10 由 CD8 ^{+ 产生}T 细胞。系统生物学方法强调，AV 引导形成一个叠瓦状网络，其特征是先天免疫和适应性免疫之间的邻域连接数量逐渐增加。在 AV 中，先天免疫和适应性免疫之间的早期串扰，随后是第 3 天的三联体 NK/CD4 ⁺ /CD8 ⁺ T 细胞，支持了后来/强大的生物标志物网络。这些发现表明，佐剂疫苗接种与协调广泛、平衡和多因素的细胞免疫事件相关，最终导致更强的 H1N1 体液免疫。