Model could improve design of vaccines, immunotherapies

October 27, 2020

The body's immune system defeats diseases by sensing foreign invaders, like bacteria or viruses, and then mounting a response against them.

But just how immune cell receptors work together to sense multiple molecules and make these decisions remained a mystery. Now, researchers at the Pritzker School of Molecular Engineering (PME) at the University of Chicago have discovered a general property for understanding how these cells sense and respond to microbial signals.

By studying how molecules impact immune cells, they found that while the effect of a single molecule does not predict the effect of two molecules together, the complexity stops there. In fact, the effect of singles and pairs of molecules can be used to predict how triplets of molecules work.

The result, led by Asst. Prof. Nicolas Chevrier and published October 27 in the journal Cell Systems, led to a more effective cancer immunotherapy in mice and could lead to more effective vaccines for both existing and novel viruses.

Key to designing vaccines

Each of the body's innate immune cells has receptors that recognize molecules from foreign pathogens. To fight off bacteria or viruses, those cells make decisions in response to complex combinations of inputs from those molecules. Though researchers have studied singular pathways, how these pathways work together is still not well understood.

Chevrier and his collaborators set out to better understand how cells integrate multiple signals into a response. Not only would it help answer a basic fundamental question of biology, it would also help design vaccines that use adjuvants, molecules that help modulate the immune system and enhance its response.

Though just a few vaccines currently use them, adjuvants might be the key to developing new kinds of vaccines. Right now, FDA-approved adjuvants target only one or two of the cell's receptors. If researchers could find the right combination to target more, vaccines could become more effective.

Understanding how combinations work together

Chevrier and his collaborators used adjuvants to stimulate immune cells in petri dishes to figure out what happens when single molecules, pairs of molecules, and triplets of molecules are used. If the results were additive, the effects of one molecule and the effects of another molecule would, when combined, remain the same. Researchers found that wasn't the case - two molecules combined together led to different effects than each had singularly.

But they did find that the effect of single molecules and pairs of molecules could accurately predict what happened with triplets of molecules.

"It could have been infinitely complex, but it's not," Chevrier said. "We are the first to show you can predict higher-order effects across immune pathways with very simple models."

Model used to design cancer immunotherapy

To prove their theory, the researchers injected cells conditioned with certain combinations of adjuvants - creating a specific cancer immunotherapy treatment - in a mouse model with tumors. The response was potent: the tumors grew five to ten times less in treated mice versus untreated mice.

"That was very encouraging," Chevrier. "Now we need to better understand the mechanisms of why this worked so well."

The researchers also hope to search for new combinations of adjuvants that have equally strong effects and eventually mount a clinical trial in humans.

"Now that we can predict the effects of multiple adjuvants with little data and a simple model, we need to extend this knowledge to the design of vaccines against both new and old threats," Chevrier said.
Other authors on the paper include Surya Pandey and Adam Gruenbaum of the University of Chicago; Tamara Kanashova and Philipp Mertins of the Max Delbrück Center for Molecular Medicine; and Philippe Cluzel of Harvard University.

University of Chicago

Related Immune System Articles from Brightsurf:

How the immune system remembers viruses
For a person to acquire immunity to a disease, T cells must develop into memory cells after contact with the pathogen.

How does the immune system develop in the first days of life?
Researchers highlight the anti-inflammatory response taking place after birth and designed to shield the newborn from infection.

Memory training for the immune system
The immune system will memorize the pathogen after an infection and can therefore react promptly after reinfection with the same pathogen.

Immune system may have another job -- combatting depression
An inflammatory autoimmune response within the central nervous system similar to one linked to neurodegenerative diseases such as multiple sclerosis (MS) has also been found in the spinal fluid of healthy people, according to a new Yale-led study comparing immune system cells in the spinal fluid of MS patients and healthy subjects.

COVID-19: Immune system derails
Contrary to what has been generally assumed so far, a severe course of COVID-19 does not solely result in a strong immune reaction - rather, the immune response is caught in a continuous loop of activation and inhibition.

Immune cell steroids help tumours suppress the immune system, offering new drug targets
Tumours found to evade the immune system by telling immune cells to produce immunosuppressive steroids.

Immune system -- Knocked off balance
Instead of protecting us, the immune system can sometimes go awry, as in the case of autoimmune diseases and allergies.

Too much salt weakens the immune system
A high-salt diet is not only bad for one's blood pressure, but also for the immune system.

Parkinson's and the immune system
Mutations in the Parkin gene are a common cause of hereditary forms of Parkinson's disease.

How an immune system regulator shifts the balance of immune cells
Researchers have provided new insight on the role of cyclic AMP (cAMP) in regulating the immune response.

Read More: Immune System News and Immune System Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to