Laboratorio di Microbiologia Molecolare e Biotecnologia (LA.M.M.B.), Dipartimento di Biotecnologie Mediche, Università di Siena, Siena, Italy.
Emory Vaccine Center, Emory University, Atlanta, GA, United States.
Front Immunol. 2018 Jun 5;9:1248. doi: 10.3389/fimmu.2018.01248. eCollection 2018.
Transcriptomic profiling of the immune response induced by vaccine adjuvants is of critical importance for the rational design of vaccination strategies. In this study, transcriptomics was employed to profile the effect of the vaccine adjuvant used for priming on the immune response following re-exposure to the vaccine antigen alone. Mice were primed with the chimeric vaccine antigen H56 of administered alone or with the CAF01 adjuvant and boosted with the antigen alone. mRNA sequencing was performed on blood samples collected 1, 2, and 7 days after priming and after boosting. Gene expression analysis at day 2 after priming showed that the CAF01 adjuvanted vaccine induced a stronger upregulation of the innate immunity modules compared with the unadjuvanted formulation. The immunostimulant effect of the CAF01 adjuvant, used in the primary immunization, was clearly seen after a booster immunization with a low dose of antigen alone. One day after boost, we observed a strong upregulation of multiple genes in blood of mice primed with H56 + CAF01 compared with mice primed with the H56 alone. In particular, blood transcription modules related to innate immune response, such as monocyte and neutrophil recruitment, activation of antigen-presenting cells, and interferon response were activated. Seven days after boost, differential expression of innate response genes faded while a moderate differential expression of T cell activation modules was appreciable. Indeed, immunological analysis showed a higher frequency of H56-specific CD4+ T cells and germinal center B cells in draining lymph nodes, a strong H56-specific humoral response and a higher frequency of antibody-secreting cells in spleen of mice primed with H56 + CAF01. Taken together, these data indicate that the adjuvant used for priming strongly reprograms the immune response that, upon boosting, results in a stronger recall innate response essential for shaping the downstream adaptive response.
疫苗佐剂诱导的免疫反应的转录组分析对于合理设计疫苗接种策略至关重要。在这项研究中，我们采用转录组学方法来分析疫苗佐剂在单独再次暴露于疫苗抗原后的免疫反应中的作用。我们用单独或与 CAF01 佐剂混合的嵌合疫苗抗原 H56 对小鼠进行了初免，并单独用抗原进行了加强免疫。在初免后 1、2 和 7 天以及加强免疫后收集血液样本进行 mRNA 测序。初免后 2 天的基因表达分析表明，与未佐剂化制剂相比，CAF01 佐剂增强了固有免疫模块的上调。在单独用低剂量抗原进行加强免疫后，明显观察到 CAF01 佐剂在初次免疫中的免疫刺激作用。加强免疫后 1 天，我们观察到用 H56+CAF01 初免的小鼠血液中有多个基因的强烈上调，而单独用 H56 初免的小鼠则没有。特别是，与先天免疫反应相关的血液转录模块，如单核细胞和中性粒细胞募集、抗原呈递细胞的激活和干扰素反应被激活。加强免疫后 7 天，先天反应基因的差异表达减弱，而 T 细胞激活模块的适度差异表达则可察觉。事实上，免疫分析显示，用 H56+CAF01 初免的小鼠引流淋巴结中 H56 特异性 CD4+T 细胞和生发中心 B 细胞的频率更高，H56 特异性体液反应更强，脾中抗体分泌细胞的频率更高。总之，这些数据表明，用于初免的佐剂强烈重编程了免疫反应，在加强免疫后，会导致更强的先天免疫回忆反应，这对于塑造下游适应性反应至关重要。
