Researchers Block Allergic Reactions to Peanuts in Mice

In a new study, researchers were successful in preventing allergic reactions to peanuts in mice using an allergen-specific inhibitor molecule. The research is published in Science Translational Medicine.

A tough nut to crack

An estimated 1.1% of the US population are thought to have severe (and possibly even fatal) allergic reactions caused by peanuts. There are no preventative treatments available, so allergy sufferers are recommended to follow strict dietary avoidance, but risks of accidental exposure are high as even trace amounts of peanuts can have disastrous consequences.

The researchers in the current study, led by Başar Bilgiçer, professor of chemical and biomolecular engineering at the University of Notre Dame, aimed to test the effectiveness of an inhibitor that could potentially be used to prevent these allergic reactions from occurring.

"Our approach is unique because our inhibitor starts working before the allergen has a chance to trigger an allergic reaction,” Bilgiçer explained. “Our collaboration with Dr. Mark Kaplan at Indiana University School of Medicine and Dr. Scott Smith at Vanderbilt University Medical Center made the development of these inhibitors possible. With their help, we were able to demonstrate the potency of our approach in animal studies.”

Slowing allergies in their tracks

Bilgiçer and colleagues used a specialized molecule called a covalent heterobivalent inhibitor (cHBI) that they had developed in a previous study. These molecules specifically block the peanut allergens from binding to antibodies on the surface of cells called immunoglobulin E (IgE), preventing them from initiating the complex series of events that lead to an allergic reaction. This effectively masks the allergen from the immune system without harming its ability to fight off infection.

When IgE antibodies encounter peanut allergens in the bloodstream of someone with an allergy, the body releases large amounts of molecules that cause inflammation, such as histamine. “The release of histamines is meant to fight against invading pathogens, but, in the case of peanut allergy, there is no pathogen, just peanut proteins,” Bilgiçer explained.

Using mice that produce human immune cells, the researchers showed that a single dose of the cHBI provided over two weeks of protection against allergic reactions to peanuts. This is an important first step to demonstrate the possibility of this working in humans.

Additionally, the cHBI was also able to slow down the progression of an allergic reaction when it was given soon after the first symptoms appeared.

Advancing to trials

Elaborating on the potential applications of these molecules, the authors explain that the research will now advance into preclinical trials, and that the success of the study indicates the development of other allergen-specific inhibitors may be possible.

“What we’ve developed is a platform technology,” said Bilgiçer. “The same design and engineering principles used in this paper can be applied in developing inhibitors to treat a range of other allergies such as shellfish and penicillin.”

Reference: Alakhras NS, Shin J, Smith SA, et al. Peanut allergen inhibition prevents anaphylaxis in a humanized mouse model. Sci. Transl. Med. 2023;15(682):eadd6373. doi: 10.1126/scitranslmed.add6373.

This article is a rework of a press release issued by the University of Notre Dame. Material has been edited for length and content.