Improvement of sublingual immunotherapy efficacy with a mucoadhesive allergen formulation.
BACKGROUND
Sublingual immunotherapy is a noninvasive and efficacious treatment of type I respiratory allergies. A murine model of sublingual immunotherapy is needed to understand better the immune mechanisms involved in successful immunotherapy and to assess second-generation candidate vaccines.


OBJECTIVE
Herein, we developed a therapeutic murine model of sublingual immunotherapy in which we document the value of mucoadhesive formulations to enhance treatment efficacy.


METHODS
BALB/c mice were sublingually treated with soluble or formulated ovalbumin before or after sensitization with ovalbumin. Airways hyperresponsiveness and lung inflammation were assessed by whole-body plethysmography and lung histology, respectively. Humoral and cellular immune responses were monitored by ELISA and ELISPOT techniques.


RESULTS
Prophylactic sublingual administration of ovalbumin completely prevents airways hyperresponsiveness as well as IL-5 secretion and IgE induction. Therapeutic administration of ovalbumin as a solution via either the sublingual or oral route has a limited efficacy. In contrast, sublingual application of ovalbumin formulated with maltodextrin to enhance mucosal adhesion results in a major reduction of established airways hyperresponsiveness, lung inflammation, and IL-5 production in splenocytes. This mucoadhesive formulation significantly enhances ovalbumin-specific T-cell proliferation in cervical but not mesenteric lymph nodes, and IgA production in the lungs.


CONCLUSIONS
A mucoadhesive maltodextrin formulation of ovalbumin enhances priming of the local mucosal immune system and tolerance induction via the sublingual route.


CONCLUSIONS
Mucoadhesive formulations offer the opportunity to improve dramatically sublingual immunotherapy in human beings, most particularly by simplifying immunization schemes.
Razafindratsita
Alain
A
Research and Development, Stallergènes, Antony, France.
Saint-Lu
Nathalie
N
Mascarell
Laurent
L
Berjont
Nathalie
N
Bardon
Thierry
T
Betbeder
Didier
D
Van Overtvelt
Laurence
L
Moingeon
Philippe
P
D000286:Administration, Sublingual; D000485:Allergens / Q000008:administration & dosage* / Q000627:therapeutic use; D000818:Animals; D001249:Asthma / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000517:prevention & control / Q000628:therapy; D001991:Bronchitis / Q000276:immunology / Q000628:therapy; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D007114:Immunization; D007070:Immunoglobulin A / Q000096:biosynthesis; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000187:drug effects; D007167:Immunotherapy / Q000379:methods*; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015848:Interleukin-5 / Q000037:antagonists & inhibitors / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D009061:Mouth Mucosa; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D020545:Respiratory Mucosa / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology; D014014:Tissue Adhesives; D016896:Treatment Outcome
D000485:Allergens; D007070:Immunoglobulin A; D015848:Interleukin-5; D014014:Tissue Adhesives; D016753:Interleukin-10; D007073:Immunoglobulin E; D010047:Ovalbumin