Current Methods to Predict the Human Immune Response

Existing methods to predict the human adaptive immune response, such as peripheral blood mononuclear cells (PBMCs) and animal models have limited effectiveness, impeding the discovery and development of vaccines and immune-related pharmaceutical products. Before discussing how MIMIC™ answers these methods' shortcomings, let's examine these existing methods in more detail here.

Peripheral Blood Mononuclear Cells (PBMCs)

One method uses human peripheral blood mononuclear cells (PBMC), which is a population of monocytes, NK cells, and T and B lymphocytes in a two-dimensional in vitro assay to simulate the immune response. The PBMCs are extracted from whole human blood by standard methods (e.g., Ficoll separation), or as a by-product from apheretic processes intended to concentrate platelets for transfusion. The PBMCs are aliquoted into test tubes or wells in a plastic plate, then stimulated with an antigen or molecules that provoke innate and/or adaptive immune responses. Benefits and drawbacks of this method are:

Benefits	Drawbacks
Uses human immune cells	2D environment
High-throughput format	Immune cell populations not segregated
Relatively inexpensive	Improper cell-cell interactions
Established process	Immune stimulants added

Using Animal Models to Simulate Human Immune Responses

Another method uses animal models to simulate a human immune response. Mice and rats are most often used in the early stages of development. Larger species, such as dogs and non-human primates, are typically used in later stages of development. Animals treated with vaccines will exhibit an immune response, which can be measured over time in various ways. Animals may also be used to test pharmaceutical products such as immune suppressants. For example, the collagen-induced arthritis model in mice is commonly used to test efficacy of products to treat rheumatoid arthritis, an autoimmune disease. However, the immune systems of animals differ significantly from the human immune system, especially when rodent models are used. Benefits and drawbacks of this method are:

Benefits	Drawbacks
3D environment	Low throughput – automation not possible
Immune cell populations segregated	Relatively expensive (especially larger animals)
Physiological response	Often not predictive of human immune response
Test toxicity effects of drug