Recent advances in the discovery and delivery of vaccine adjuvants.
Recent advances in the discovery and delivery of vaccine adjuvants.
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DOI：
10.1038/nrd1176
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发表时间：
2003-09
期刊：
影响因子：
--
通讯作者：
Valiante NM
中科院分区：
文献类型：
--
作者：
O'Hagan DT;Valiante NM
佐剂是一个术语，用于描述与疫苗共同施用的多种成分，可增强疫苗抗原的免疫原性。根据其主要作用机制，这些成分可大致分为两个子集：递送系统和免疫增强剂。先天免疫系统的细胞、受体和信号通路是改进递送系统和免疫增强剂的重要目标。宿主防御的整合模型表明，抗原特异性记忆的最佳生成（疫苗接种的目标）需要先天免疫激活。阐明先天免疫激活机制以及先天反应和适应性反应之间联系的最新进展表明，许多天然和合成化合物具有特定的免疫增强活性。这些化合物有望成为下一代疫苗佐剂。酰亚胺喹啉类 SMIP（小分子免疫增强剂）的鉴定为 Toll 样受体依赖性，表明小分子平台可用于免疫增强剂的设计和发现。疫苗递送系统用于确保疫苗中包含的抗原和免疫增强剂能够与适当的组织或细胞相互作用，以促进有效免疫反应的诱导。事实证明，可生物降解的微粒对于疫苗抗原和佐剂来说都是有吸引力的递送系统。粘膜疫苗递送系统专门设计用于使疫苗成功应用于粘膜表面，主要涉及口服或鼻内给药。粘膜递送系统的重要组成部分包括旨在保护抗原免于降解并促进其与粘膜相关淋巴组织相互作用的成分。由于依赖于先天免疫激活的复杂生物学，佐剂设计历来具有炼金术的核心。然而，对先天免疫的新机制理解，加上利用这些知识的新佐剂和递送平台，最近取得了重大进展。尽管仍然存在许多挑战，但该领域正在迅速发展，并且已经有了适当的工具和方法来使用传统药物发现引擎来指导疫苗佐剂的开发。在这篇综述中，我们概述了免疫增强剂、递送系统和佐剂设计的当前趋势，这些趋势将塑造未来的疫苗。
Adjuvant is a term used to describe a variety of components co-administered with a vaccine that enhance the immunogenicity of vaccine antigens. These components can be broadly divided into two subsets on the basis of their dominant mechanism of action: delivery systems and immune potentiators. The cells, receptors and signalling pathways of the innate immune system are important targets for improved delivery systems and immune potentiators. The integrated model of host defence indicates that optimal generation of antigen-specific memory (the goal of vaccination) requires innate immune activation. Recent advances in elucidating the mechanisms of innate immune activation and the links between innate and adaptive responses have shown that numerous natural and synthetic compounds possess specific immune-potentiating activities. These compounds have promise as next generation vaccine adjuvants. The identification of the imidizaquinoline class of SMIPs (small-molecule immune potentiators) as Toll-like receptor-dependent indicate that the small-molecule platform could be exploited for immune potentiator design and discovery. Vaccine delivery systems are used to ensure that the antigens and immune potentiators included in a vaccine are able to interact with the appropriate tissues or cells to promote the induction of a potent immune response. Biodegradable microparticles are proving to be attractive delivery systems for both vaccine antigens and adjuvants. Mucosal vaccine delivery systems are specifically designed to allow vaccines to be successfully applied to mucosal surfaces, mostly involving oral or intranasal administration. Important elements of mucosal delivery systems include components designed to protect antigens from degradation and to promote their interaction with mucosal-associated lymphoid tissue. Adjuvant design has historically had a touch of alchemy at its heart due to its reliance on the complex biology of innate immune activation. However, a new mechanistic understanding of innate immunity, combined with new adjuvant and delivery platforms for exploiting this knowledge, has led to significant advances recently. Although many challenges remain, the field is moving rapidly and the proper tools and methodologies are in place for the use of traditional drug discovery engines in guiding the development of vaccine adjuvants. In this review, we outline the current trends in immune potentiator, delivery system and adjuvant design that will shape the vaccines of the future.
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影响因子：
5.5
作者：
Jegerlehner, A;Tissot, A;Bachmann, MF
通讯作者：
Bachmann, MF
影响因子：
168.9
作者：
Dilraj, A;Cutts, FT;Bennett, JV
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影响因子：
--
作者：
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HORAN, JM
影响因子：
3.1
作者：
Baudner, BC;Balland, O;Del Giudice, G
通讯作者：
Del Giudice, G
影响因子：
5.1
作者：
Denis-Mize, KS;Dupuis, M;Ott, G
通讯作者：
Ott, G