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首页> 外文期刊>Vaccine >Bis-(3 ',5 ')-cyclic dimeric adenosine monophosphate: Strong Th1/Th2/Th17 promoting mucosal adjuvant
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Bis-(3 ',5 ')-cyclic dimeric adenosine monophosphate: Strong Th1/Th2/Th17 promoting mucosal adjuvant

机译：双-（3'，5'）-环二聚腺苷单磷酸酯：强Th1 / Th2 / Th17促进粘膜佐剂

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摘要

New effective adjuvants are required to improve the performance of subunit vaccines. Here, we showed that bis-(3',5')-cyclic dimeric adenosine monophosphate (c-di-AMP), a second messenger molecule in bacteria and archaea, exerts strong adjuvant activities when delivered by mucosal route. In vitro studies showed that c-di-AMP was able to both stimulate pre-activated murine macrophages and promote the activation and maturation of dendritic cells of murine and human origin. Co-administration of c-di-AMP with beta-galactosidase (beta-Gal) by intranasal route to BALB/c mice resulted in the elicitation of significantly higher serum antigen-specific IgG titres than in controls. The induction of local immune responses was shown by the production of antigen-specific secretory IgA in different mucosal territories. In addition, strong cellular immune responses were observed against both the beta-Gal protein and a peptide encompassing its MHC class I-restricted epitope. The ratio of beta-Gal-specific antibodies and the secreted cytokine profiles by in vitro re-stimulated splenocytes suggested that a balanced Th1/Th2/Th17 response pattern is promoted by c-di-AMP. When C57BL/6 mice were immunized with OVA and c-di-AMP, vigorous in vivo CTL responses were also observed. These results indicated that c-di-AMP exhibits a high potential as adjuvant for the development of mucosal vaccines, in particular when cellular immunity is needed
机译：需要新的有效佐剂来改善亚单位疫苗的性能。在这里，我们显示了双-（3'，5'）-环二聚腺苷单磷酸腺苷（c-di-AMP），细菌和古细菌中的第二个信使分子，当通过粘膜途径传递时发挥强大的佐剂活性。体外研究表明，c-di-AMP既能刺激预活化的鼠巨噬细胞，又能促进鼠和人来源树突状细胞的活化和成熟。通过鼻内途径向BALB / c小鼠与c-di-AMP和β-半乳糖苷酶（β-Gal）共同给药，导致引起的血清抗原特异性IgG滴度明显高于对照组。通过在不同的粘膜区域中产生抗原特异性分泌型IgA，表明了局部免疫应答的诱导。另外，观察到针对β-Gal蛋白和包含其MHC I类限制性表位的肽的强细胞免疫应答。 β-Gal特异性抗体的比例和体外再刺激脾细胞分泌的细胞因子谱表明，c-di-AMP可促进平衡的Th1 / Th2 / Th17反应模式。当用OVA和c-di-AMP免疫C57BL / 6小鼠时，也观察到了强烈的体内CTL反应。这些结果表明，c-di-AMP作为粘膜疫苗开发的佐剂具有很高的潜力，尤其是在需要细胞免疫的情况下

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