Fel d 1 Peptide Immunotherapy Ameliorates Both Cat and Ovalbumin Responses, in a Dual Allergen Murine Model of Allergic Airways Disease

Rationale: Peptide Immunotherapy targeting Fel d 1, the primary cat allergen, is clinically efficacious and has been shown to facilitate the spread of tolerance between T-cell epitopes within Fel d 1 through the generation of a tolerogenic environment. We sought to further explore the potential of the tolerogenic environment. Specifically, we hypothesized that Fel d 1 peptide immunotherapy could ameliorate responses to an unrelated, but co-administered, allergen.

Methods: Female BALB/c mice (Charles River;6-8wks, n=4/group, two independent experiments) received two intraperitoneal injections of Fel d 1 (1µg) and ovalbumin (OVA; 10µg) in alum (D0 & 14). Peptides Fel d 1_23-38 (EQVAQYKALPVVLENA) and Fel d 1_29-45 (KALPVVLENARILKNCVDAK) were administered intradermally on D28, 35 and 42. Mice were then concurrently exposed to OVA and Fel d 1, subcutaneously (D49, 56 & 63). Parallel groups of mice were challenged intranasally with either cat dander extract (CDE) or OVA, to assess the immune response to each allergen. 24-hour post challenge, mice were sacrificed and bronchoalveolar lavage (BAL), lungs and draining lymph nodes were collected for assessment by cytology, histology and flow cytometry.

Results: CDE and OVA challenge of sham treated mice induced robust airway eosinophilia. Peptide therapy prevented CDE-induced eosinophilia, while expanding T- and B-regulatory populations. Fel d 1 peptide immunotherapy also protected mice from challenge with OVA, observed as reductions in eosinophil recruitment and inflammatory cytokine (IL-4, -5 and -17) production by T-cells.

Conclusions: These results indicate that protection established with Fel d 1 peptide immunotherapy can be extended to other co-administered allergens, thereby potentially extending clinical efficacy.