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

SOTO A; MATÍAS DAMIÁN PERRONE SIBILIA; VANESA ROXANA SÁNCHEZ; NADIA ARCÓN; VALENTINA MARTIN; IGNACIO MARTÍN FENOY; ALEJANDRA GOLDMAN

INTL. ARCH. ALLERGY IMMUNOL.

Karger

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 alternativetreatment to control asthma that still presents several concerns related to its formulation. rTgPI-1contains independent inhibitory domains able to inhibit trypsin and neutrophil elastase, bothinvolved in asthma pathology. Objectives: In view of the need to design rational therapies, herein weinvestigate 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 OVAcombined with the full-length recombinant protein rTgPI-1 or its truncated versions, Nt (containingtrypsin 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 allinhibitory domains were simultaneously administered, an improvement was achieved. Still, a betteroutcome was obtained when mice were treated with the full-length rTgPI-1. Conclusions: Adjuvantability 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.