Cell Interaction and Timing in the MIMIC™ System

Sometimes individuals fail to show a response when tested with in vitro models of human immunity. VaxDesign is trying to understand why this occurs, so that we can develop a more predictive immune model. With the help of our research partners, we've been able to determine what cells are important in the immune response, and that it's not enough to simply place the right combinations of cells in the right environment to achieve accurate and truly predictive immune responses. Not only are those variables — cell types and cell environment — important to a functional MIMIC™ system, but also the timing of the interactions between the cell-cell interactions plays an important role.

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The data show that spatiotemporal relationships that mimic normal immunophysiology are key components of predictive and robust in vitro immune responses. Modeling these spatiotemporal relationships is a major feature of MIMIC™ technology.

As one example, under physiologic conditions within lymph nodes, the generation of antigen-specific T cells by DCs in the paracortexusually precedes the induction of specific B cell responses in the cortex. We find that the stimulation of adaptive responses in vitro is also enhanced by mimicking a similar sequence of temporal/kinetic events.

We find that timing of the interaction of different cell populations influences the outcome of the culture in vitro. We delayed the addition of B lymphocytes to cell cocultures; this modification markedly improved the proliferation and activation of both T and B cells. The data shown shows enhanced influenza specific Ab production due to the delayed culture.