Intralymphatic Injections as a New Administration Route for Allergen-Specific Immunotherapy

Abstract

Background: IgE-mediated allergy can be treated by subcutaneous allergen-specific immunotherapy (SIT). However, the percentage of allergic patients undergoing SIT is low, mainly due to the long duration of the therapy and the risk of severe systemic allergic reactions associated with the allergen administration. To improve the safety and attractiveness of SIT for patients, alternative routes of allergen administration are being explored, such as sub-lingual or oral administration. Methods: The present study evaluated direct intralymphatic allergen administration as a means to enhance SIT with bee venom and cat fur allergens in mice. Allergen-specific antibody and T-cell responses were analysed by ELISA and flow cytometry. The therapeutic potential of intralymphatic immunisation in sensitised mice was analysed using an anaphylaxis model. Results: Direct injection of the major bee venom allergen phospholipase A₂ or the major cat fur allergen Fel d 1 into inguinal lymph nodes enhanced allergen-specific IgG and T-cell responses when compared with subcutaneous injections. Moreover, only intralymphatic immunisation stimulated the production of the Th1-dependent subclass IgG2a, which is associated with improved protection against allergen-induced anaphylaxis. Biodistribution studies showed that injection into the lymph node delivered antigen more efficiently to subcutaneous lymph nodes than subcutaneous injection. Conclusions: As intralymphatic immunisation induced more than 10-fold higher IgG2a responses with 100-fold lower allergen doses than subcutaneous immunisation, this approach should allow to reduce both the number of allergen injections as well as the allergen dose, improving both efficacy and safety of SIT.

New routes for allergen immunotherapy

“…132 Similar results were obtained in humans when intralymphatic injections were compared with subcutaneous injection using radio tracing. 81,83 Essentially, when the same dose of a 99mTc labeled protein was injected into either a superficial inguinal lymph node or subcutaneously at a site just lymphocytes are so low (approximately one in ten million) that antigens must be presented to millions of T and B cells in order to find their match and to elicit a response.…”

“…In mice, we have demonstrated that ILIT with a variety of allergens, e.g., bee venom phospholipase-A2, ovalbumin and allergen extracts from grass pollen, birch pollen and cat dander, stimulated antiallergic and protective B-and T-cell immune responses. [130][131][132][133][134] In fact, changing from the subcutaneous route to direct intralymphatic injection significantly enhanced the efficacy of immunization, inducing allergen-specific IgG2a antibody responses that were 10-20 times higher with only 0.1% of the allergen dose. Since allergic side effects are proportional to the allergen dose, intralymphatic SIT should also have the potential to reduce side effects, as lower doses of allergens are required for efficacious SIT.…”

Specific immunotherapy in grass pollen allergy

“…9 Finally, a new promising route of administration has been recently explored with intralymphatic allergen injections. 10 In humans, 3 injections in a lymph node seems to be as efficient on rhinoconjunctivitis symptoms as three years of subcutaneous immunotherapy. 11…”

Food Allergy Diagnosis and Therapy: Where are we Now?

“…It has shown great promise, having much greater efficacy than SCIT in far fewer doses, inducing stronger immune responses without polarizing T-cell responses [146,149,150]. Its use in FA therapy has yet to be assessed, although it has been found effective in a mouse model of ovalbumin allergy [146], and its efficacy in aeroallergen therapy suggests it is an avenue worth pursuing.…”