Department of Pharmaceutical Technology, University Regensburg, Regensburg, Germany.
Department of Experimental Ophthalmology, University Marburg, Marburg, Germany.
Eur J Pharm Biopharm. 2023 Dec;193:119-128. doi: 10.1016/j.ejpb.2023.10.008. Epub 2023 Oct 12.
The complement system plays a central role in our innate immunity to fight pathogenic microorganisms, foreign and altered cells, or any modified molecule. Consequences of complement activation include cell lysis, release of histamines, and opsonization of foreign structures in preparation for phagocytosis. Because nanoparticles interact with the immune system in various ways and can massively activate the complement system due to their virus-mimetic size and foreign texture, detrimental side effects have been described after administration like pro-inflammatory responses, inflammation, mild to severe anaphylactic crisis and potentially complement activated-related pseudoallergy (CARPA). Therefore, application of nanotherapeutics has sometimes been observed with restraint, and avoiding or even suppressing complement activation has been of utmost priority. In contrast, in the field of vaccine development, particularly protein-based immunogens that are attached to the surface of nanoparticles, may profit from complement activation regarding breadth and potency of immune response. Improved transport to the regional lymph nodes, enhanced antigen uptake and presentation, as well as beneficial effects on immune cells like B-, T- and follicular dendritic cells may be exploited by strategic nanoparticle design aimed to activate the complement system. However, a shift of paradigm regarding complement activation by nanoparticular vaccines can only be achieved if these beneficial effects are accurately elicited and overshooting effects avoided.
补体系统在我们的先天免疫中起着核心作用，可以抵御致病微生物、外来和改变的细胞，或任何修饰的分子。补体激活的后果包括细胞溶解、组胺释放以及对外来结构的调理作用，为吞噬作用做准备。由于纳米颗粒以类似于病毒的大小和外来纹理与免疫系统相互作用，并可能因大规模激活补体系统而产生有害的副作用，如促炎反应、炎症、轻度至重度过敏性危象以及潜在的补体激活相关假性过敏（CARPA）。因此，纳米疗法的应用有时受到限制，避免甚至抑制补体激活已成为当务之急。相比之下，在疫苗开发领域，特别是与纳米颗粒表面结合的蛋白质免疫原，可以从补体激活中受益，提高免疫反应的广度和效力。通过策略性的纳米颗粒设计，改善向区域淋巴结的输送、增强抗原摄取和呈递，以及对 B、T 和滤泡树突状细胞等免疫细胞的有益影响，可以利用补体系统的激活。然而，如果要实现纳米颗粒疫苗补体激活的范式转变，就必须准确地引发这些有益作用，并避免过度反应。
