Poveda Cristina, Biter Amadeo B, Bottazzi Maria Elena, Strych Ulrich
Department of Pediatrics, National School of Tropical Medicine, Baylor College of Medicine, One Baylor Plaza, BCM113 Houston, TX 77030, USA.
Texas Children's Hospital Center for Vaccine Development, Baylor College of Medicine, 1102 Bates Street, Houston, TX 77030, USA.
Vaccines (Basel). 2019 Sep 27;7(4):131. doi: 10.3390/vaccines7040131.
The preferred product characteristics (for chemistry, control, and manufacture), in addition to safety and efficacy, are quintessential requirements for any successful therapeutic. Messenger RNA vaccines constitute a relatively new alternative to traditional vaccine development platforms, and thus there is less clarity regarding the criteria needed to ensure regulatory compliance and acceptance. Generally, to identify the ideal product characteristics, a series of assays needs to be developed, qualified and ultimately validated to determine the integrity, purity, stability, and reproducibility of a vaccine target. Here, using the available literature, we provide a summary of the array of biophysical and biochemical assays currently used in the field to characterize mRNA vaccine antigen candidates. Moreover, we review various in vitro functional cell-based assays that have been employed to facilitate the early assessment of the biological activity of these molecules, including the predictive immune response triggered in the host cell. Messenger RNA vaccines can be produced rapidly and at large scale, and thus will particularly benefit from well-defined and well-characterized assays ultimately to be used for in-process, release and stability-indications, which will allow equally rapid screening of immunogenicity, efficacy, and safety without the need to conduct often lengthy and costly in vivo experiments.
除安全性和有效性外，理想的产品特性（化学、控制和生产方面）是任何成功治疗手段的基本要求。信使核糖核酸（mRNA）疫苗是传统疫苗开发平台的一种相对较新的替代方案，因此在确保监管合规和获批所需的标准方面尚不够清晰。一般来说，为确定理想的产品特性，需要开发一系列检测方法，进行鉴定并最终验证，以确定疫苗靶点的完整性、纯度、稳定性和可重复性。在此，我们利用现有文献，总结了该领域目前用于表征mRNA疫苗抗原候选物的一系列生物物理和生化检测方法。此外，我们还综述了各种基于细胞的体外功能检测方法，这些方法已被用于促进对这些分子生物活性的早期评估，包括宿主细胞中触发的预测性免疫反应。mRNA疫苗能够快速大规模生产，因此最终用于生产过程、放行和稳定性检测的明确且特征良好的检测方法将使其特别受益，这将能够同样快速地筛选免疫原性、有效性和安全性，而无需进行通常耗时且昂贵的体内实验。
