An “inverse vaccine” that delivers deactivated allergens to the liver was able to reduce reactions in mice with allergic asthma for at least a year after treatment. Should the approach translate to humans, people with allergies may one day be able to take a vaccine that protects them from dangerous allergic reactions.
Mice allergic to either an egg protein or a dust mite protein saw their airway inflammation and mucus levels reduced after exposure if they’d been given the vaccine, researchers reported in Science Translational Medicine on April 16.
For mice with an established egg protein allergy, a commonly used model for respiratory allergies, protection lasted for a full year after two intravenous doses of the vaccine separated by a week, the researchers found.
“One thing I really like about this approach is that it has memory,” Jeffrey Hubbell, Ph.D., a biomedical engineer at New York University and senior author of the study, told Fierce Biotech in an interview. “You just take the drug and then that's that.”
How often a human version of the vaccine would need to be given is something Hubbell hopes to work out in clinical trials. He’s weighing whether to start a new biotech or to partner with an existing company to further explore the approach, but he's determined to move the therapy forward somehow, he said.
The inverse vaccine is essentially a safer and faster version of allergy immunotherapy, Hubbell said, which involves exposing people with allergies to small amounts of an allergen over time to build up their body’s ability to handle exposure.
“Low amount of allergen can potentially drive tolerance in individuals,” J. Emiliano Gómez Medellín, Ph.D., a molecular biologist at the University of Chicago Pritzker School of Molecular Engineering and an author of the study, told Fierce Biotech in an interview. But exposing someone to the thing they’re allergic to can also cause trouble, he added, by triggering an inflammatory response, including dangerous anaphylaxis.
To make the allergens safer, the researchers used an engineering approach to stick a mannose sugar onto them, nullifying the parts of their protein structures that trigger an allergic response. This turns the allergen into what the scientists call a “tolerogen.”
Because the liver is able to produce long-lasting regulatory T cells, which can calm the overactive helper T cells that spark allergic reactions, the team directed their innocuous tolerogens there. Once in the liver, the tolerogens induce the organ to make regulatory T cells that quell the response to that specific allergen.
The technique is called an inverse vaccine because rather than inhibiting a bad actor, like a virus, “we're promoting a good actor,” the regulatory T cells, Hubbell said.
Hubbell has worked on related liver-targeting tech for years, co-founding the Swiss biotech Anokion in 2010 that is now pushing forward inverse vaccines for autoimmune diseases like celiac disease and multiple sclerosis. Anokion’s celiac disease candidate, KAN-101, recently proved able to reduce gluten-triggered symptoms in early phase 2 data.
Medellín is now working on adapting the allergic asthma vaccine for food allergies, he said, with preliminary mouse data so far showing the technique may confer protection there too.
Hubbell wants to get the vaccine “rock solid” in defending against allergens found in peanuts or cow’s milk, he said, so that when looking to advance the therapy he can show its overall potential to protect against any protein allergen.
“To go out and say, 'hey, look, we can work in respiratory allergy, we can work in food allergies,'” Hubbell explained, would suggest the vaccine is "quite a generalizable concept.”