Our immune system recreated on a chip to study the effectiveness of vaccines


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Vaccines came back on tea in front of a scientific scene during a sober pandemic COVID-03. Our knowledge of the immune system and the mechanisms involved are however still limited to us, despite undeniable advances. Nevertheless, the differences in the reaction of organisms (of different individuals) to the same disease make the task particularly difficult when it comes to the development of a vaccine, for example. Indeed, why do some people show no symptoms when infected with SARS-CoV-2 while others suffer from specialty fever and body aches? Researchers at Harvard’s Wyss Company have created a more accurate model of the human immune system in a microfluidic chip, providing a better platform to study how immune cells respond to vaccines and pathogens. Explanations.

New vaccines and immunotherapies are currently being evaluated in animal models , which may result in unintended toxicities or poor efficacy in human clinical trials, due to species differences in immune responses. Admittedly, preclinical experiments can be carried out in vitro using human immune cells taken from blood; however, even these results often fail to predict patient reactions.

One of the main reasons for this failure is that immune responses inside vivo ze usually occur in the highly specialized tissue microenvironment of lymphoid follicles. They are small groups of tissues containing nafed W and To lymphocytes, which together initiate the cascade of events leading to a full immune response which, when exposed to the specific antigen. They normally exist in secondary lymphoid organs such as the lymph nodes. But they may ectopically (in other organs) cause swelling. It is the understanding of this adaptive immune response that is at stake in the implementation of vaccines or immunotherapies in humans. Opinion having access to these mechanisms depends on the surrounding tissue which?

In recent years, scientists have developed a simple way to model organs and other bodily tissues. in microfluidic chips, allow much closer comparison that. A microfluidic chip is a set of microchannels etched or molded in the material (glass, silicon or polymer). The microchannels are interconnected to fulfill a specific function (sorting, pumping, mixing, etc.). These organs on chips or Organ-On-Chip (OOC) included until now the heart, the lungs, the intestines, the kidneys, the price, the horn, the dings and the placenta.

La Protection Advanced Analysis Projects Company, an agency of the United States Department of Defense for research and development of new technologies for military use, supported the engineering of a device that fluidically links multiple OOCs to create a body-on-chip that. The latter should make it possible to study the impact of drugs on several organ systems simultaneously. Recently, researchers from Harvard University’s Wyss Start for Biologically Motivated Anatomist, also supported by that US Department of Defense, added the immune system to the list of these OOCs. Their research is published in the journal Advanced Technology.

An unexpected discovery

Before this technological feat, the sober Goyal team simply wanted to study how B and Capital t lymphocytes, circulating in the blood, modify their behavior once inside a tissue. For this purpose, they cultured these immune cells, from samples of human blood, inside a microfluidic device, designed to mimic the situations they encounter when they reach the organ.

b t cell microfluidic chip
Une illustration des canaux microfluidiques, contenant des cellules B et T humaines (roses et vertes) dans la partie infrieure. Institut Wyss l’Universit de Harvard

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A representation of the microfluidic channels, containing human B and Big t cells (pink and green) in a part lower. Wyss Institute at Harvard University

But when researchers introduced the nutrient flow, they discovered some unexpected select. The M cells and Testosterone levels began to organize themselves into three-dimensional structures that resembled lymphoid follicles and, more specifically, they seemed to form germinal cells, carry out immune reactions, things that.

Goyal, an immunologist at the Wyss Company and sober primary author on the study, said in a statement:

It was so unexpected that we completely diverted soberly from the original experience and focused on this discovery .

This is how, by probing the constructions formed, they were able to observe which secreted a chemical compound called CXCL13. The latter is produced by lymphoid follicles in response to chronic irritation. In addition, the N cells inside the buildings expressed an enzyme called activation-induced cytidine deaminase (Help), essential for activating T cells against specific antigens. This enzyme is not present in Udemærket lymphocytes circulating in the blood. National insurance CXCL National Insurance Help were present in cells grown out of these chips, suggesting that scientists were indeed successful in creating functional lymphoid follicles from blood cells in blood flow.

They also found plasma cells in which the mature B cells learned to differentiate in order to secrete antibodies, after having applied several stimuli, such as a sober combination of a cytokine IL-4 and an anti-CD antibody 19, or dead bacteria.

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formation of lymphoid follicles microfluidic chip
B and P cells formed clumps that resembled lymphoid follicles as nutrients passed through the routine (left), but not in static problems (right). Wyss Institute at Harvard University

Pranav Prabhala, technician at Wyss Start and co-author of the article, specifies: These findings were particularly exciting, as they confirmed that we have a working model that could be used to unravel some of the complexities of the human immune system, including its responses to various types of pathogens.

A tool to predict the effectiveness vaccines

In a 2nd temperature, with a simple model of functional lymphoid follicles and capable of triggering an immune response, they sought to know his opinion that he would respond to a vaccination. That’s why the team added dendritic cells. To their effect, in the body they help produce antigens, presenting pieces of pathogens to the lymph nodes. Then they vaccinated that on-chip immune system against the They Would5In1 flu strain either alone or with the adjuvant, called SWE, known to boost immune responses to the vaccine. The chips that received the vaccine and the adjuvant produced significantly more plasma cells and antibodies against influenza than those grown in the usual culture dishes, and even compared to those that only received the vaccine without the adjuvant.

This indicates that these lymphoid follicle microfluidic chips are a close match to reality. They could provide a model much more similar to the human body, for future research on the immune system and the development of drugs.

Researchers from Wyss is now using their lymphoid follicle arrays to test various vaccines and adjuvants in collaboration with pharmaceutical companies and the Gates Foundation.

G. Goyal concludes:

Animals have been the gold standard research models for developing and testing new vaccines, but their immune system differs significantly from ours and does not predict not sure how humans will respond to it. Our chip
[de follicules lymphoïdes]

offers a way to model the complex choreography of human immune responses to infection and vaccination, and could significantly speed up the pace and the quality of vaccine creation in the future .

Source: Advanced Science