REVIEW article
Front. Immunol.
Sec. Vaccines and Molecular Therapeutics
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1584852
This article is part of the Research TopicTowards the Rapid and Systematic Assessment of Vaccine TechnologiesView all 8 articles
Methods integrating innate and adaptive immune responses in human in vitro immunization assays
Provisionally accepted
- Los Alamos National Laboratory (DOE), Los Alamos, New Mexico, United States
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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), monocytederived 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.
Keywords: In vitro immunization, innate immunity, Adaptive Immunity, Whole blood assay, microphysiological human tissue construct assay, monocyte-derived dendritic cell assay, dendritic cell-T cell interface assay, vaccine development
Received: 27 Feb 2025; Accepted: 05 May 2025.
Copyright: © 2025 Bowley, Lenz, Shanker and Kubicek-Sutherland. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jessica Z. Kubicek-Sutherland, Los Alamos National Laboratory (DOE), Los Alamos, 87545, New Mexico, United States
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