Cyclic di-nucleotides: new era for small molecules as adjuvants.
Cyclic di-nucleotides: new era for small molecules as adjuvants.
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DOI：
10.1111/j.1751-7915.2011.00306.x
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发表时间：
2012-03
影响因子：
5.7
通讯作者：
Guzmán CA
中科院分区：
文献类型：
--
作者：
Libanova R;Becker PD;Guzmán CA
甚至在卫生和抗菌药物出现在医疗实践之前，就已经将疫苗接种作为预防传染病的经验性策略而引入。然而，直到几十年前，我们才真正开始了解疫苗接种引发的潜在保护机制。疫苗最初是基于减毒或灭活的生物体。随后，亚单位疫苗作为更精细的配方被引入，表现出改进的安全性。然而，纯化的抗原往往免疫原性较差，并且通常需要使用佐剂来实现对免疫系统的充分刺激。疫苗接种策略，例如粘膜给药，也需要有效的佐剂来提高性能。 20 世纪 90 年代，免疫学家发现病原体可以被识别保守基序的受体感知为“危险信号”。尽管我们的知识仍然有限，但在理解这些进化保守受体调节的宿主防御机制以及它们识别的分子结构方面取得了巨大进展。这开启了佐剂开发的新纪元。进入该领域的一些最新参与者是环状二核苷酸，它们是普遍存在的原核细胞内信号分子。本次综述的重点是它们开发疫苗和免疫疗法的潜力。
The implementation of vaccination as an empiric strategy to protect against infectious diseases was introduced even before the advent of hygiene and antimicrobials in the medical practice. Nevertheless, it was not until a few decades ago that we really started understanding the underlying mechanisms of protection triggered by vaccination. Vaccines were initially based on attenuated or inactivated organisms. Subunit vaccines were then introduced as more refined formulations, exhibiting improved safety profiles. However, purified antigens tend to be poorly immunogenic and often require the use of adjuvants to achieve adequate stimulation of the immune system. Vaccination strategies, such as mucosal administration, also require potent adjuvants to improve performance. In the 1990s, immunologists found that pathogens could be sensed as ‘danger signals’ by receptors recognizing conserved motifs. Although our knowledge is still limited, tremendous advances were made in the understanding of host defence mechanisms regulated by these evolutionary conserved receptors, and the molecular structures which are recognized by them. This opened a new era in adjuvant development. Some of the latest players arrived to this field are the cyclic di‐nucleotides, which are ubiquitous prokaryotic intracellular signalling molecules. This review is focused on their potential for the development of vaccines and immunotherapies.
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