Novel adjuvants for B cell immune responses
Novel adjuvants for B cell immune responses
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DOI：
10.1097/coh.0b013e32832da082
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发表时间：
2009-09-01
影响因子：
4.1
通讯作者：
Hedestam, Gunilla B. Karlsson
中科院分区：
文献类型：
--
作者：
Lore, Karin;Hedestam, Gunilla B. Karlsson
综述目的总结佐剂开发的最新进展，特别关注增强 B 细胞对蛋白质疫苗反应的佐剂。描述了已建立的和新的实验方法，并简要讨论了佐剂和基于病毒的疫苗如何与免疫系统相互作用。最新发现两种新佐剂最近被批准用于人类应用，许多其他佐剂正在进行临床前或临床测试。在描述佐剂作用机制方面取得了重大进展。例如，氢氧化铝盐被证明可以与 Nalp3（胞质 NOD 样受体的成员）结合，并且描述了通过不变的自然杀伤细胞呈递 α-半乳糖神经酰胺来激活 B 细胞。 Toll 样受体配体对 B 细胞分化的影响得到了进一步表征，并且源自 IPS-1（一种胞质信号分子）的肽被证明可以提供佐剂作用。针对 HIV-1 的保护性抗体的刺激可能需要广泛的抗体亲和力成熟，因此可能需要长期暴露或重复施用抗原来诱导有效的 B 细胞反应。总结我们对特定信号通路如何连接先天免疫和适应性免疫的理解的进展为设计改进的佐剂以促进广泛而有效的 B 细胞反应奠定了基础。
Purpose of reviewTo summarize recent progress in the development of adjuvants with a special focus on adjuvants that enhance B-cell responses to protein-based vaccines. Both established and new experimental approaches are described and also briefly we discuss how adjuvants and virus-based vaccines interact with the immune system.Recent findingsTwo new adjuvants were recently approved for human applications and many others are in preclinical or clinical testing. Significant advances were made to describe the mechanism of action of adjuvants. For example, aluminum hydroxide salts were shown to engage Nalp3, a member of the cytosolic NOD-like receptors and activation of B cells via invariant natural killer cell presentation of alpha-galactosylceramide was described. The effects of Toll-like receptor ligands on B-cell differentiation were further characterized and a peptide derived from IPS-1, a cytosolic signaling molecule, was shown to provide adjuvant effect. Stimulation of protective antibodies against HIV-1 may require extensive antibody affinity maturation, thus long-term exposure or repeated administration of antigen may be needed to induce effective B-cell responses.SummaryAdvances in our understanding of how specific signaling pathways link innate and adaptive immunity provides a basis for the design of improved adjuvants to promote broad and potent B-cell responses.