Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Curr Opin HIV AIDS. 2009 Sep;4(5):441-6. doi: 10.1097/COH.0b013e32832da082.
To 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.
Two 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.
Advances 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.
总结佐剂研发的最新进展,特别关注增强基于蛋白疫苗的 B 细胞反应的佐剂。描述了既定的和新的实验方法,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。
最近有两种新佐剂被批准用于人体应用,还有许多其他佐剂正在进行临床前或临床试验。佐剂作用机制的描述取得了重大进展。例如,已经证明氢氧化铝盐能够与胞质 NOD 样受体家族成员 Nalp3 结合,并通过天然杀伤细胞(NKT)呈递α-半乳糖神经酰胺激活 B 细胞。还进一步描述了 Toll 样受体配体对 B 细胞分化的影响,并证明源自胞质信号分子 IPS-1 的肽可提供佐剂效应。刺激针对 HIV-1 的保护性抗体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给予抗原以诱导有效的 B 细胞反应。
我们对特定信号通路如何将先天免疫和适应性免疫联系起来的理解的进展为设计改良佐剂以促进广泛而有效的 B 细胞反应提供了基础。