Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
Department of Pathology, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
Nat Rev Drug Discov. 2021 Jun;20(6):454-475. doi: 10.1038/s41573-021-00163-y. Epub 2021 Apr 6.
Adjuvants are vaccine components that enhance the magnitude, breadth and durability of the immune response. Following its introduction in the 1920s, alum remained the only adjuvant licensed for human use for the next 70 years. Since the 1990s, a further five adjuvants have been included in licensed vaccines, but the molecular mechanisms by which these adjuvants work remain only partially understood. However, a revolution in our understanding of the activation of the innate immune system through pattern recognition receptors (PRRs) is improving the mechanistic understanding of adjuvants, and recent conceptual advances highlight the notion that tissue damage, different forms of cell death, and metabolic and nutrient sensors can all modulate the innate immune system to activate adaptive immunity. Furthermore, recent advances in the use of systems biology to probe the molecular networks driving immune response to vaccines ('systems vaccinology') are revealing mechanistic insights and providing a new paradigm for the vaccine discovery and development process. Here, we review the 'known knowns' and 'known unknowns' of adjuvants, discuss these emerging concepts and highlight how our expanding knowledge about innate immunity and systems vaccinology are revitalizing the science and development of novel adjuvants for use in vaccines against COVID-19 and future pandemics.
佐剂是增强免疫反应的幅度、广度和持久性的疫苗成分。自 20 世纪 20 年代问世以来，明矾是接下来 70 年中唯一获准用于人类的佐剂。自 20 世纪 90 年代以来，又有五种佐剂被纳入许可疫苗中，但这些佐剂的作用机制仍部分未知。然而，我们对通过模式识别受体（PRR）激活先天免疫系统的理解的革命性进展正在提高对佐剂的机制理解，最近的概念进展强调了这样一种观点，即组织损伤、不同形式的细胞死亡以及代谢和营养传感器都可以调节先天免疫系统以激活适应性免疫。此外，最近在利用系统生物学来探测驱动疫苗免疫反应的分子网络（“系统疫苗学”）方面的进展正在揭示机制见解，并为疫苗发现和开发过程提供了新的范例。在这里，我们回顾了佐剂的“已知的已知”和“已知的未知”，讨论了这些新出现的概念，并强调了我们对先天免疫和系统疫苗学的不断增长的认识如何使针对 COVID-19 和未来大流行的新型佐剂的科学和开发焕发生机。
