Contribution of Kazal-like domains of the serine-protease inhibitor-1 from T. gondii in asthma therapeutic vaccination effectiveness

A SOTO; M PERRONE SIBILIA; SANCHEZ VR; ARCÓN, N; MARTIN V; FENOY I,; A GOLDMAN

INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY

KARGER

Lugar: Basel; Año: 2022

1018-2438

Background: We previously showed rTgPI-1 tolerogenic adjuvant properties in asthma treatment, turning it a promising candidate for allergen-specific immunotherapy. This therapy is an alternative treatment to control asthma that still presents several concerns related to its formulation. rTgPI-1 contains independent inhibitory domains able to inhibit trypsin and neutrophil elastase, both involved in asthma pathology. Objectives: In view of the need to design rational therapies, herein we investigate the contribution of the different inhibitory domains in rTgPI-1 therapeutic effectiveness. Methods: BALB/c mice were rendered allergic by intraperitoneal OVA-alum sensitization and airway-challenged. Once the asthmatic phenotype was achieved, mice were intranasally treated with OVA combined with the full-length recombinant protein rTgPI-1 or its truncated versions, Nt (containing trypsin inhibitory domains) or Ct (containing neutrophil elastase inhibitory domains). Afterward, mice were aerosol re-challenged. Results: Asthmatic mice treated with the neutrophil elastase or the trypsin inhibitory domains separately, failed to improve allergic lung inflammation. Only when all inhibitory domains were simultaneously administered, an improvement was achieved. Still, a better outcome was obtained when mice were treated with the full-length rTgPI-1. Conclusions: Adjuvant ability depends on the presence of all its inhibitory domains in a single entity so it should be included in potential asthma treatment formulations as a full-length protein.