在过去的十年里,由于其安全性和免疫原性,人们对基于铁蛋白的疫苗的兴趣日益增加.针对多种病原体的候选人现在正在进行第一阶段临床试验,即针对流感,爱泼斯坦-巴尔,和SARS-CoV-2病毒。与颗粒异质性相关的制造挑战,融合抗原的不正确折叠,和对亚单位间相互作用的抗原干扰仍然需要克服。此外,协议需要标准化,以便生产生物过程变得可重复,允许基于铁蛋白的疗法变得容易获得。在这次审查中,能够在实验阶段配制基于铁蛋白的疫苗的结构单元,包括设计,生产,并进行了纯化。基于模块化组装功能化铁蛋白纳米颗粒的新型生物工程策略,允许与遗传融合相关的挑战被规避,正在讨论。比较了生产基于铁蛋白的疫苗的不同的上/下游方法及其对产量和疫苗功效的影响。最后,综述了目前铁蛋白纳米颗粒在疫苗开发和临床试验中的应用。
In the last decade, the interest in ferritin-based vaccines has been increasing due to their safety and immunogenicity. Candidates against a wide range of pathogens are now on Phase I clinical trials namely for influenza, Epstein-Barr, and SARS-CoV-2 viruses. Manufacturing challenges related to particle heterogeneity, improper folding of fused antigens, and antigen interference with intersubunit interactions still need to be overcome. In addition, protocols need to be standardized so that the production bioprocess becomes reproducible, allowing ferritin-based therapeutics to become readily available. In this review, the building blocks that enable the formulation of ferritin-based vaccines at an experimental stage, including design, production, and purification are presented. Novel bioengineering strategies of functionalizing ferritin nanoparticles based on modular assembly, allowing the challenges associated with genetic fusion to be circumvented, are discussed. Distinct up/down-stream approaches to produce ferritin-based vaccines and their impact on production yield and vaccine efficacy are compared. Finally, ferritin nanoparticles currently used in vaccine development and clinical trials are summarized.