The MIMIC™ Process

We can create a quiescent endothelium on top of a collagen matrix in a 96 well format, and this comprises the heart of our vaccination site. We have shown that monocytes can selectively extravasate through the endothelium into the collagen matrix, without adding any exogenous factors. These monocytes can then spontaneously differentiate into antigen presenting cells, such as macrophages and dendritic cells.

The endothelium can be activated with various inflammatory signals such as interleukin (IL)-1β or TNFα.

The antigen-pulsed dendritic cells are then placed into the lymphoid tissue equivalent, where they can interact and activate T cells. We have shown that the Ag-pulsed DCs can activate both CD8+ and CD4 cells. The CD4 helper T cells have been shown to stimulate the B cells, activate them, and differentiate them into Ab secreting plasma cells.

The following steps make up most of the MIMIC™ system's predictive processes:

1. Monocytes extravasate through the endothelium.
2. Monocytes differentiate into immature DCs within hours.
3. Those immature DCs mature during challenge antigen, immunotherapy, immunostimulant, biologic, etc. and maturation signal presentation.
4. Mature DCs reverse transmigrate through the endothelium and are then placed in the lymphoid tissue equivalent to activate naïve and/or memory T and B cells
5. The immunocytes and biomolecules from the LTE are characterized (ELISA, ELIspot, FACS, etc) for immune responses and then tested for immune functionality in various assays (hemagglutinin inhibition, microneutralization Ab assays, CTL responses, etc.)