PME researcher receives NIH funding to study vaccine combination adjuvants

Nicolas Chevrier, assistant professor at the Pritzker School of Molecular Engineering (PME) at the University of Chicago, has received $2 million in direct funding from the National Institutes of Health (NIH) to support his research on vaccine adjuvants. With the new grant, Chevrier will investigate the mechanisms that enable adjuvant triplet combinations to affect the immune system.

The grant, officially part of the Molecular Mechanisms of Combination Adjuvants (MMCA) program, was created to promote the understanding of novel adjuvant combinations. Adjuvants are a class of highly specialized compounds used in vaccines to influence the body’s response, often boosting a person’s immune reaction. Currently, only a handful of adjuvants are used in modern vaccines.

Nicolas Chevrier
Asst. Prof. Nicolas Chevrier

Because of their ability to boost vaccine effectiveness, the National Institute of Allergy and Infectious Disease (NIAID) considers adjuvant development a high-priority research area, and in 2016, they initiated the MMCA program. The program’s goal is to understand and potentially develop new combination adjuvants to improve vaccine responses in compromised populations such as young children and the elderly.

“This NIH award will allow us to break new ground on fundamental mechanisms in the immune system, which is very exciting,” Chevrier said. “Our work in 2020 demonstrated how a better understanding of how multiple signaling pathways coordinate their actions can directly improve treatment. Now, with this funding, we can take an even deeper dive into the mechanistic implications of that work.”

Chevrier’s previous research focused on the cellular mechanisms behind adjuvant responses, breaking down how cells communicate when confronted with the specialized compounds. His broader research focuses on how the immune system communicates on multiple scales, from the cellular level up to the whole organism, which he believes is essential to developing more effective clinical treatments.

“Our motivation is learning the fundamental rules about how the immune system works in an integrated fashion,” Chevrier said. “Typically, people might study just immune molecules in cells, or specific subsets of immune cells in a specific tissue, whereas we try to emphasize a multiscale approach by studying the effects of molecules on cells, tissues, and even the whole body. By better understanding those fundamental rules governing the immune system, we hope to better manipulate it.”

One of the main challenges facing vaccine adjuvant research is the sheer number of potential combinations to evaluate. If a team was researching 1,000 potential compounds, Chevrier explained, it would mean testing roughly 40 billion possible combinations. That many combinations equate to running about 100,000 experiments a day for 1,000 years.

Chevrier sidesteps that obstacle by investigating how to better predict the effects of adjuvant combinations on immune responses, eliminating the need to test thousands of compounds. Already, Chevrier and his team have used this approach to successfully predict an adjuvant combination that shrunk tumor growth in mouse models of melanoma.

Looking to the future, Chevrier hopes that what his team uncovers in the coming years will lead to transformative applications in the fundamental and translational spaces.

“We do all these things in the hope that within the next five to ten years, perhaps we can contribute knowledge that will help bring new adjuvant combinations to the clinic in one form or another,” Chevrier said. “We want to help grow an arsenal of adjuvants, make better vaccines for diseases we already know, and help cope with diseases that have yet to come or that are currently intractable.”