Bowley Tetiana Y, Lenz Kiersten D, Shanker Apoorv, Kubicek-Sutherland Jessica Z
Physical Chemistry and Applied Spectroscopy, Chemistry Division, Los Alamos National Laboratory, Los Alamos, NM, United States.
Front Immunol. 2025 May 21;16:1584852. doi: 10.3389/fimmu.2025.1584852. eCollection 2025.
Rapid vaccine development and innovative immunotherapeutics are critical in the fight against emerging outbreaks and global pandemic threats, yet the high costs and prolonged timelines for developing new vaccines underscore the urgent need for robust, predictive pre-clinical testing platforms. The rapid down-selection of vaccine candidates and identification of optimal vaccine formulations can be performed using human immunization (IVI) assays that recapitulate the complex interactions of the innate and adaptive human immune response. In this review, we present a comprehensive evaluation of three key IVI platforms: the whole blood assay (WBA), monocyte-derived dendritic cell (MoDC) assay with dendritic cell-T cell interface assay (DTI), and the microphysiological human tissue construct assay (HTC). The WBA offers a cost-effective and straightforward approach, while the MoDC + DTI system represents the current gold standard for balancing experimental efficiency with immunological complexity. The HTC assay, by mimicking both spatial and temporal aspects of immune interactions, provides enhanced physiological relevance. We discuss the methodological advantages and limitations of each platform, explore their roles in rapid vaccine candidate screening, and propose strategies for integrating these assays with complementary models. These insights pave the way for refining IVI assays and accelerating the translational pipeline for next-generation vaccines and immunotherapies.
快速的疫苗研发和创新的免疫疗法对于抗击新出现的疫情和全球大流行威胁至关重要，然而开发新疫苗的高成本和漫长时间线凸显了对强大的、具有预测性的临床前测试平台的迫切需求。可以使用模拟人类先天和适应性免疫反应复杂相互作用的人体免疫（IVI）测定法，对候选疫苗进行快速筛选并确定最佳疫苗配方。在本综述中，我们对三个关键的IVI平台进行了全面评估：全血测定法（WBA）、具有树突状细胞 - T细胞界面测定法（DTI）的单核细胞衍生树突状细胞（MoDC）测定法以及微生理人体组织构建体测定法（HTC）。WBA提供了一种经济高效且直接的方法，而MoDC + DTI系统是在实验效率与免疫复杂性之间取得平衡的当前金标准。HTC测定法通过模拟免疫相互作用的空间和时间方面，提供了更高的生理相关性。我们讨论了每个平台的方法学优势和局限性，探讨了它们在快速筛选候选疫苗中的作用，并提出了将这些测定法与互补模型整合的策略。这些见解为完善IVI测定法以及加速下一代疫苗和免疫疗法的转化流程铺平了道路。
