Video: How the MIMIC System Works

Transcription

VaxDesign is developing a “clinical trial in a test tube” that simulates the human immune response in a high-throughput method.

This simulated immune response enables rapid, clinically relevant predictions about the efficacy of immunotherapies and vaccines which can dramatically reduce the cost and time required to bring these products to market.

Our immune simulation method has four steps:

1. Blood Collection via Apheresis
2. the Vaccination Site Module [Peripheral Tissue Module]
3. the Lymphoid Tissue Equivalent Module
4. and Functional Assays

Step 1: Blood Collection via Apheresis

The first step in our process is blood collection and preparation. In collaboration with Florida’s Blood Centers, we collect white blood cells from pre-screened donors using leukopheresis.

VaxDesign takes the white blood cells and processes them into either purified PBMCs, or isolated sub-populations of the PBMCs such as monocytes, T cells, and B cells.

Step 2: Vaccination Site Module

The second step is the construction of the Vaccination Site module, which mimics human skin or peripheral tissue for a representation of innate responses. We prepare 96-well plates seated with a collagen layer covered with a human cell endothelium. Each of the wells is effectively one human test subject.

The purified PBMCs or monoctyes from Step 1 are placed on top of this endothelium. The monocytes selectively migrate through the endothelium and excess cells are washed off after an hour. After migration, they spontaneously differentiate into subsets of antigen-presenting cells with a range of phenotypes such as dendritic cells or macrophages.

The dendritic cells reverse-transmigrate through the endothelium, mimicking traffic across the lymphatics.

After reverse transmigration, we expose the DCs to test antigen or vaccine, and extract the antigen-pulsed dendritic cells using a pipette.

Some now-potent antigen-presenting cells are then placed into the next module: the lymphoid tissue equivalent or LTE.

Step 3: Lymphoid Tissue Equivalent (LTE) Module

The Lymphoid Tissue Equivalent module is a co-culture of t cells, b cells, and follicular dendritic cells that simulates a lymph node to initiate adaptive immune responses. When the dendritic cells present their antigen to the right receptor-matched T cells, a chain reaction occurs. The antigen activates T cells, which can then activate B cells. These B cells can then differentiate to plasma cells, generating antibodies and other cytokines.

We can examine both cellular and humoral immune responses to an individual. After a week for a recall immunological response and about two weeks for a naive immunological response, we remove the immunocytes and biomolecules for analysis.

Step 4: Functional Assays

The final step is the characterization of these immunocytes and biomolecules using a wide range of assays such as ELISA, ELISpot, ICCS, cytotoxic T cell, and neutralizing antibody assays.

Using antibody responses as an example, we can determine:

• Class
• Subtype
• Subclass
• Specificity,
• and Virus neutralization

Shown here, the vaccine-generated antibodies opsonize the virus stopping it from entering into the cellular host.

Our clinical trial in a test tube mirrors the human immune system more closely than any other model available. It simulates chemical efficacy of an immunotherapy or vaccine on human population subgroups, rapidly and consistently.

These results enable the design of more rapid and incisive clinical trials, potentially reducing the time and costs to produce new drugs and vaccines.