Monash University scientists have identified an immune system power play behind serious bee venom allergy, which lands twice as many Australians in hospital emergency departments each year as snake or spider bites.

According to the latest AIHW databee allergies were the number one cause of hospitalizations caused by venomous animals in 2021–22 with 1,072 cases—outstripping 539 visits for snake envenomation, and 455 for spider bites.

The standard preventive treatment, bee venom immunotherapy, is effective in up to 80% of recipients, but takes about three years to confer maximum protection. Unfortunately, for up to 15% of people with bee venom allergy, receiving immunotherapy actually induces anaphylaxis. And 1 in 5 recipients lose any benefit within 12 months of ending treatment.

In a paper published in the Journal of Allergy and Clinical Immunologya team led by Dr. Craig McKenzie of the Monash School of Translational Medicine revealed a surprising new finding that could solve the puzzle of how immunotherapy can cure allergies.

The key lies in the interplay between two types of antibodies and how they engage with an incoming allergen: IgG antibodies quietly neutralize by surrounding allergens in a sort of headlock; while IgE antibodies “overreact,” unleashing allergic reactions such as hives, rash and anaphylaxis.

“We used to think that people with bee venom allergies simply didn’t create enough of the ‘good’ IgG antibodies,” Dr. McKenzie said.

“What we found was that they usually do have them, but that they need even more than was previously thought necessary. Crucially, they need to outnumber IgE antibodies, in a process called ‘competitive inhibition,’ but even that doesn’t work for all patients.

“We also found that where an IgG antibody can grab at the allergen, it might play a crucial protective role against severe allergic reactions.”

The findings suggest that immunotherapies may work better by attaching to the allergen all over its surface, rather than just a part of it, as is the case in current formulations. This opens up new angles to improve therapies in the future.

A second challenge uncovered by this research is how to stoke IgG levels so that they crowded out IgEs. This requires stepping back to examine the behavior of the cells that go on to make these antibodies: Type 2 B cells. These are memory cells of the immune system that in recent years have been identified as the cells that create both these types of antibodies.

“Figuring out what makes type 2 B cells create either IgG or IgE is the next challenge. We’re looking for the switch,” Dr. McKenzie said.

The study builds on previous work on rye grass allergy, which uncovered the same mechanism. The research has implications for the widespread phenomenon of vaccines and immunotherapy waning over time.

“Bee venom immunotherapy has been around for decades, and when it works, it works really well,” Dr. McKenzie said.

“But there is still a significant group of people for whom it doesn’t work, and others who lose any benefits pretty quickly once they finish a long, expensive and invasive treatment requiring them to have regular injections for years.

“Living with bee venom allergy means living with a lot of uncertainty. You can only ever be sure immunotherapy has worked if you end up getting stung and don’t get anaphylaxis. It means you still have considerable anxiety around bees because you never truly know until you get stung.

“Knowing more about how these cells work will help us get better at predicting whether and how immunotherapy works in certain people, and unlocking longer-lasting benefits in the hope of curing other allergies in addition to bee venom allergies.”