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Immune system on a chip will speed up the development of new vaccines

Researchers at the Harvard Wyss Institute have modified a microfluidic chip model of the human immune system, providing better conditions for studying how immune cells respond to vaccines and pathogens. This could speed up the development of new vaccines.

The scientists cultured human B and T cells inside a microfluidic device designed to mimic the physical conditions these immune cells would encounter when they reached the organ. When the nutrient stream was added inside, something unexpected was found, the scientists said.

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B and T cells formed clumps resembling lymphoid follicles when nutrients flowed around the circuit (left) but not under static conditions (right)

By culturing human B and T cells inside a microfluidic device and adding nutrients to them, the scientists discovered the formation of germinal centers that trigger complex immune responses. The grown lymphoid follicles secreted the chemical CXCL13, which is normally produced in response to chronic inflammation. B cells within the structures expressed an enzyme called activation-induced cytidine deaminase (AID), which activates B cells against certain antigens. Also found are plasma cells into which mature B cells differentiate to secrete antibodies.

“These results are particularly exciting because they confirm that we have a functional model that can be used to unravel some of the complexities of the human immune system, including how it responds to different types of pathogens,” said Pranav Prabhala, co-author of the study.

The scientists then tested how the artificial immune system would react to vaccination by adding dendritic cells involved in the production of antigens to the microfluidic chip. The H5N1 influenza strain was taken for the experiment, and, of course, the vaccinated LF chips produced much more plasma cells and anti-flu antibodies than those grown in conventional squamous cell cultures.

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Illustration of microfluidic channels containing human B and T cells (pink and green) at the bottom

Identical results were also found in experiments with commercially available influenza vaccines. It was found that the level of some cytokines is similar to what happens in vaccinated people. This indicates that LF microfluidic chips are close in their work to real immune centers inside living organisms. In turn, it follows that they can become a much more humane analogue of animal experiments for future immunological research and drug development.

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