Experimental Immunotherapy Could Offer Some Protection Against Insect Sting-Induced Anaphylaxis

Research using mouse models may offer clues to potential prophylactic approaches for patients with venom sensitivity.

New research in mice may offer hope for people whose severe allergies to stings put them at risk of anaphylaxis.

A team from Switzerland gave CBA/J mice prophylactic injections of a compound that binds the allergen phospholipase A2 (PLA2) to microbubbles (MB). They then measured antibody and T cell response of each mouse with ELISA and CFSE-based proliferation assays and, finally, injected the mice with native PLA2 in order to simulate bee stings.

Escalating doses of native PLA2 eventually killed all of the mice, but the prophylactic shot significantly reduced the severity of allergic reactions.

“Prophylactic immunization with PLA2-MB induced PLA2-specific IgG and IgA Ab, triggered the production of IFN-γ and IL-10, and the differentiation of PLA2-specific Foxp3+ Treg,” the study authors wrote in Clinical & Experimental Allergy.

“Immunized/sensitized mice displayed: (1) increased titers of potent blocking IgG1, IgG2a and IgG3 Ab, (2) both reduced allergen-specific T cell proliferation and Th2-type cytokine production and (3) elevated frequencies of specific Foxp3+ Treg and increased production of TGF-β, as compared to naïve/sensitized animals.Immunomodulation correlated with reduced signs of anaphylaxis after allergen challenge.”

The researchers noted that the treatment protected mice against PLA2 for at least 4 months and credited the microbubble formulation for the effect. Indeed, they speculated that microbubble technology might allow the creation of similar prophylactic products targeted at a wide range of allergens.

Venom sensitivity is common. Roughly 25% of Americans exhibit it to some degree, and it tends to increase with each exposure.

A research review published in Immunology and Allergy Clinics of North America estimates that stings have triggered anaphylaxis in 3% of all Americans. Anaphylaxis typically occurs in people who have developed venom sensitivity from previous stings, but it can occur the first time a person ever gets stung.

Trials of venom immunotherapy have found it to be between 75% and 98% effective in reducing the risk of anaphylaxis. It is, however, a cumbersome form of protection. A full course of immunotherapy lasts anywhere from 3 years to 5 years, and patients must adhere to it religiously in order to enjoy its full benefits.

A formula that could provide significant protection against venom after just 1 injection — or even after a handful of injections — would therefore constitute a significant improvement over the status quo, an improvement that might induce a far higher percentage of venom-sensitive patients to protect themselves.

The researchers who tested the PLA2-MB formulation in mice consisted of 2 researchers from the Division of Immunology and Allergy at University State Hospital (CHUV) in Epalinges, Switzerland and 3 others from Bracco Suisse SA, a company that already uses microbubbles in contrasting agents for medical imaging.

A number of pharmaceutical companies around the world are working on experimental treatments that seek to expedite traditional immunotherapy. None of them has been approved for widespread use, but a skin patch designed to reduce the risk of anaphylaxis and other severe reactions to peanuts has become the first allergy treatment ever granted a place in the US Food and Drug Administration’s program for “breakthrough” products.