Evidence for cyclic diguanylate as a vaccine adjuvant with novel immunostimulatory activities
Evidence for cyclic diguanylate as a vaccine adjuvant with novel immunostimulatory activities
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DOI：
10.1016/j.cellimm.2012.07.006
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发表时间：
2012-07-01
影响因子：
4.3
通讯作者：
Vora, Kalpit A.
中科院分区：
文献类型：
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作者：
Gray, Peter M.;Forrest, Gail;Vora, Kalpit A.
环二鸟苷酸（c-di-GMP）是一种细菌信号分子，在细菌攻击模型中具有保护性免疫刺激活性。本研究探索了c-di-GMP作为疫苗佐剂的潜力，将其与LPS、CpG寡核苷酸和常规的基于铝盐的佐剂进行比较。在该评价中，c-di-GMP是体液和Th 1样免疫应答的更有效的激活剂，如其在小鼠中诱导的强IgG 2a抗体应答和强IFN-γ所证明的。TNF-α和IP-10应答，在小鼠和体外非人灵长类动物外周血单核细胞中引起。此外，与LPS或CpG相比，c-di-GMP在免疫小鼠中表现出更显著的诱导生发中心形成的能力，这是长期记忆的标志。总之，这些数据增加了越来越多的证据，支持c-di-GMP作为佐剂在疫苗接种中用于持续和稳健的免疫应答，并为在适当的免疫模型中进行进一步评价提供了依据。(C)2012 Elsevier Inc. All rights reserved.
Cyclic diguanylate (c-di-GMP), a bacterial signaling molecule, possesses protective immunostimulatory activity in bacterial challenge models. This study explored the potential of c-di-GMP as a vaccine adjuvant comparing it with LPS, CpG oligonucleotides, and a conventional aluminum salt based adjuvant. In this evaluation, c-di-GMP was a more potent activator of both humoral and Th1-like immune responses as evidenced by the robust IgG2a antibody response it induced in mice and the strong IFN-gamma. TNF-alpha and IP-10 responses, it elicited in mice and in vitro in non-human primate peripheral blood mononuclear cells. Further, compared to LPS or CpG, c-di-GMP demonstrated a more pronounced ability to induce germinal center formation, a hallmark of long-term memory, in immunized mice. Together, these data add to the growing body of evidence supporting the utility of c-di-GMP as an adjuvant in vaccination for sustained and robust immune responses and provide a rationale for further evaluation in appropriate models of immunization. (C) 2012 Elsevier Inc. All rights reserved.