Journal Article Review Epublish
PubMed: 40469296 DOI: 10.3389/fimmu.2025.1584852
Methods integrating innate and adaptive immune responses in human in vitro immunization assays.
Front Immunol 16:1584852
Authors: Tetiana Y Bowley, Kiersten D Lenz, Apoorv Shanker, Jessica Z Kubicek-Sutherland
Affiliations
- Physical Chemistry and Applied Spectroscopy, Chemistry Division, Los Alamos National Laboratory, Los Alamos, NM, United States.
Abstract
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 in vitro 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 in vivo models. These insights pave the way for refining IVI assays and accelerating the translational pipeline for next-generation vaccines and immunotherapies.
MeSH
Cells, Immunization, Vaccines, Adaptive Immunity, Immunity, Dendritic Cells, Immunity, Innate, T-Lymphocytes, Vaccine Development