Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
Front Immunol. 2022 Jun 29;13:910022. doi: 10.3389/fimmu.2022.910022. eCollection 2022.
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 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.
佐剂对于疫苗的发展至关重要，特别是基于亚单位的疫苗，如那些包含重组蛋白的疫苗。增加对佐剂引起的免疫反应机制的了解，应该有助于未来疫苗的制定。本工作描述了聚肌苷酸（Poly (I:C)）和 Montanide ISA 720 在以环子孢子蛋白（PvCSP）序列为基础的重组蛋白免疫小鼠的情况下诱导的免疫表型。用重组蛋白加 Montanide ISA 720 免疫的小鼠表现出总体上更强大的体液反应，诱导出对抗原具有更高亲和力的抗体。在 Montanide 佐剂处理的小鼠中，混合 Th1/Th2 炎症细胞因子谱呈增加趋势，而在 Poly (I:C) 佐剂处理的小鼠中则观察到平衡的谱。Montanide ISA 720 在 B 淋巴细胞中诱导了一个特征为血红素生物合成的基因特征，表明向浆细胞的分化增加。另一方面，Poly (I:C) 在 T 细胞转录组中引起了更多的扰动。这些结果扩展了对不同类别佐剂诱导的特定免疫反应的调节的理解，并可能支持亚单位疫苗的优化。
