The development of vaccines and immunotherapeutics is hampered by the lack of appropriate in vitro assays by which to test these compounds against the human immune system. By recognizing the key cellular elements (concentration and types of cells, cell motility, media, multicellular interactions, spatiotemporal cellular kinetics, cell expansion, and geometries) of immune tissues, such as the lymph node, we believed that we could recapitulate immune function in a biomimetic model of the human immune system, termed Modular Immune In vitro Construct (MIMIC®). We describe here the process we undertook to develop the MIMIC system by considering engineering design principles, the selection of cells to populate the system, immune functionality, the development of new antibody assays, and tissue construct automation. We also describe our approach toward using relevant challenges, such as influenza, as exemplars of different facets of immunity to test and validate the system. Through evaluating the MIMIC system with various experimental studies, we have demonstrated that the platform has the capacity to replicate known human immune response profiles. For example, we show here that influenza vaccine-induced antibody responses generated in a young adult and in the elderly donors in the MIMIC system can replicate the well-recognized immunosuppressed state of elderly donors. As well, we show the ability of the system to generate responses against variant antigens that are consistent with the response profiles observed in humans, but not in experimental animals. We believe that these studies highlight the potential of the MIMIC system for assessing human immune responses and suggest that it can serve as an ideal platform to disrupt translational research by reducing the time and cost requirements to bring new therapies to the clinic and the marketplace.
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