环鸟苷酸-腺苷酸在小鼠中表现出黏膜佐剂活性。
Cyclic GMP-AMP displays mucosal adjuvant activity in mice.
作者信息
Škrnjug Ivana, Guzmán Carlos Alberto, Rueckert Christine
机构信息
Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
出版信息
PLoS One. 2014 Oct 8;9(10):e110150. doi: 10.1371/journal.pone.0110150. eCollection 2014.
The recently discovered mammalian enzyme cyclic GMP-AMP synthase produces cyclic GMP-AMP (cGAMP) after being activated by pathogen-derived cytosolic double stranded DNA. The product can stimulate STING-dependent interferon type I signaling. Here, we explore the efficacy of cGAMP as a mucosal adjuvant in mice. We show that cGAMP can enhance the adaptive immune response to the model antigen ovalbumin. It promotes antigen specific IgG and a balanced Th1/Th2 lymphocyte response in immunized mice. A characteristic of the cGAMP-induced immune response is the slightly reduced induction of interleukin-17 as a hallmark of Th17 activity--a distinct feature that is not observed with other cyclic di-nucleotide adjuvants. We further characterize the innate immune stimulation activity in vitro on murine bone marrow-derived dendritic cells and human dendritic cells. The observed results suggest the consideration of cGAMP as a candidate mucosal adjuvant for human vaccines.
最近发现的哺乳动物酶环磷酸鸟苷-腺苷合酶在被病原体来源的胞质双链DNA激活后会产生环磷酸鸟苷-腺苷(cGAMP)。该产物可刺激依赖于干扰素基因刺激蛋白(STING)的I型干扰素信号传导。在此,我们探讨了cGAMP作为小鼠黏膜佐剂的功效。我们发现,cGAMP可增强对模型抗原卵清蛋白的适应性免疫反应。它能促进免疫小鼠产生抗原特异性IgG以及平衡的Th1/Th2淋巴细胞反应。cGAMP诱导的免疫反应的一个特点是,作为Th17活性标志的白细胞介素-17的诱导略有降低,这是一个与其他环状二核苷酸佐剂不同的显著特征。我们进一步在体外对小鼠骨髓来源的树突状细胞和人树突状细胞的固有免疫刺激活性进行了表征。观察结果表明,可考虑将cGAMP作为人类疫苗的候选黏膜佐剂。