Short-course AIT in a porcine allergic model by enhanced and prolonged
allergen presentation using a novel mucoadhesive patch approach
Abstract
Background: To assess an improved version of sublingual AIT performed by
applying a novel short-course oromucosal allergen administration
strategy in a translational allergic pig model by prolonged and enhanced
tolerogenic presentation of intact allergen with a novel mucoadhesive
patch technology. Methods: Newborn piglets sensitized intraperitoneally
with the common egg allergen ovalbumin (OVA) were sublingually treated
five times using a dose ascending administration schedule with
nanofiber-based mucoadhesive patches carrying OVA allergen, formulated
with immune tolerogenic particles derived from the probiotic bacterium
Lactococcus lactis (TBP). Immunologic assessment was conducted by the
use of the intradermal test of immediate allergic reactions to OVA.
Results: Five weekly treatments with the mucoadhesive patch carrying OVA
alone or OVA and TBP resulted in significant desensitisation, being 8%
and 45% respectively, as measured by intradermal testing. Mucoadhesive
patch-based administration of OVA together with TBP resulted in the
allergen localisation to submucosa tissue and draining lymph nodes and
resulted in better desensitization compared with patch containing OVA
allergen alone. Conclusion: A first demonstration of short-course SLIT
approach which we term Specific Oromucosal Immunotherapy (SOMIT) has
been successfully carried out in a new translational therapeutic porcine
model of allergy. The results suggest that an improved short-course SLIT
approach is feasible by prolonging allergen delivery using a
mucoadhesive patch and proper stimulation of a privileged tolerogenic
immune compartment by tolerogenic probiotic bacterial particles.