Induction of Tolerance via the Sublingual Route: Mechanisms and Applications

Table 1

Compared characteristics of sublingual versus other administration routes for allergy vaccines.

Routes	Current clinical indications	Comments	Ref
Sublingual (SLIT)	(i) Established as a safe and efficacious treatment for IgE-dependent respiratory allergies (rhinoconjunctivitis with or without moderate asthma); (ii) For adults and 5–15 year old children	(i) No adjuvants; (ii) Dose 50 to 100 fold the one used for SCIT; (iii) Treatments available as drops, fast-dissolving tablets, lyocs); (iv) Two sublingual grass pollen tablets (Grazax, Oralair) have been registered in Europe as pharmaceutical specialties); (v) Excellent safety record (mostly moderate local reactions). Systemic reactions are extremely rare); (vi) Efficacy documented by large scale double blind placebo controlled Phase III trials (evidence-based medicine)	[5–8]
Subcutaneous	(i) Same as SLIT; (ii) Venom allergies; (iii) Latex allergies	(i) Adjuvants (aluminum salts or calcium phosphate) are being used; (ii) For effective immunotherapy, a 5 to 25 μg maintenance dose of allergen is necessary; (iii) Efficacy documented by historical practice (reference route since 1911); (iv) Potential safety issues (besides acceptable local reactions, risk of infrequent but life threatening anaphylactic shocks).	[3, 4]
Exploratory routes (oral, nasal, epicutaneous, intralymphatic)	(i) None as of today; (ii) Numerous clinical studies are being conducted in patients with respiratory allergies (mites, pollens) or food allergies (milk, egg, peanut)	(i) Encouraging results in small cohorts of patients; (ii) Safety and efficacy remain to be confirmed in large scale clinical studies.; (iii) Expected positive outcomes of those new routes include new applications for immunotherapy (e.g., food allergy for the oral or epicutaneous routes) or tolerance induction with a limited number of administrations (e.g., intralymphatic route)	[9–20]