Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20850, USA.
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
J Control Release. 2021 Jan 10;329:299-315. doi: 10.1016/j.jconrel.2020.12.001. Epub 2020 Dec 5.
The development of successful vaccines has been increasingly reliant on the use of immunoadjuvants - additives, which can enhance and modulate immune responses to vaccine antigens. Immunoadjuvants of the polyphosphazene family encompass synthetic biodegradable macromolecules, which attain in vivo activity via antigen delivery and immunostimulation mechanisms. Over the last decades, the technology has witnessed evolvement of next generation members, expansion to include various antigens and routes of administration, and progression to clinical phase. This was accompanied by gaining important insights into the mechanism of action and the development of a novel class of virus-mimicking nano-assemblies for antigen delivery. The present review evaluates in vitro and in vivo data generated to date in the context of latest advances in understanding the primary function and biophysical behavior of these macromolecules. It also provides an overview of relevant synthetic and characterization methods, macromolecular biodegradation pathways, and polyphosphazene-based multi-component, nanoparticulate, and microfabricated formulations.
成功疫苗的开发越来越依赖于免疫佐剂的使用——添加剂，可以增强和调节疫苗抗原的免疫反应。多膦嗪家族的免疫佐剂包含合成可生物降解的大分子，通过抗原传递和免疫刺激机制在体内发挥作用。在过去的几十年中，该技术见证了新一代成员的发展，扩展到包括各种抗原和给药途径，并进展到临床阶段。这伴随着对作用机制的重要见解的获得，并开发了一类用于抗原传递的新型病毒模拟纳米组装体。本综述评估了迄今为止在理解这些大分子的主要功能和物理行为方面的最新进展背景下产生的体外和体内数据。它还概述了相关的合成和表征方法、大分子生物降解途径以及基于多膦嗪的多组分、纳米颗粒和微加工制剂。
