DataSheet_2_Immune System Modulation by the Adjuvants Poly (I:C) and Montanide ISA 720.pdf

Adjuvants are essential for vaccine development, especially subunit-based vaccines such as those containing recombinant proteins. Increasing the knowledge of the immune response mechanisms generated by adjuvants should facilitate the formulation of vaccines in the future. The present work describes the immune phenotypes induced by Poly (I:C) and Montanide ISA 720 in the context of mice immunization with a recombinant protein based on the Plasmodium vivax circumsporozoite protein (PvCSP) sequence. Mice immunized with the recombinant protein plus Montanide ISA 720 showed an overall more robust humoral response, inducing antibodies with greater avidity to the antigen. A general trend for mixed Th1/Th2 inflammatory cytokine profile was increased in Montanide-adjuvanted mice, while a balanced profile was observed in Poly (I:C)-adjuvanted mice. Montanide ISA 720 induced a gene signature in B lymphocytes characteristic of heme biosynthesis, suggesting increased differentiation to Plasma Cells. On the other hand, Poly (I:C) provoked more perturbations in T cell transcriptome. These results extend the understanding of the modulation of specific immune responses induced by different classes of adjuvants, and could support the optimization of subunit-based vaccines.

佐剂对于疫苗的研发至关重要，尤其是基于亚单位疫苗，例如包含重组蛋白的疫苗。增进对佐剂所引发的免疫反应机制的了解，应有助于未来疫苗的配方设计。本研究描述了在以间日疟原虫子孢子蛋白（PvCSP）序列为基础的重组蛋白免疫小鼠的背景下，Poly (I:C) 和 Montanide ISA 720 所诱导的免疫表型。接受重组蛋白与 Montanide ISA 720 共同免疫的小鼠显示出更为显著的体液反应，并诱导出对抗原具有更高亲和力的抗体。Montanide 佐剂小鼠的 Th1/Th2 混合型炎症细胞因子谱呈现上升趋势，而 Poly (I:C) 佐剂小鼠则表现出平衡的细胞因子谱。Montanide ISA 720 在 B 淋巴细胞中诱导出特征性的血红素生物合成基因标志，提示向浆细胞分化的增加。另一方面，Poly (I:C) 在 T 细胞转录组中引起更多的扰动。这些结果扩展了对不同类别的佐剂所诱导的特定免疫反应调节机制的理解，并可能支持亚单位疫苗的优化。