Improvement of sublingual immunotherapy efficacy with a mucoadhesive allergen formulation

Oral myeloid cells uptake allergoids coupled to mannan driving Th1/Treg responses upon sublingual delivery in mice

“…Allergen uptake by oral mucosal dendritic cells (DCs) is thought to be a critical step for initiating the immune response in SLIT,11 a step requiring higher allergen concentration and dose frequency for SLIT than SCIT 12. To improve allergen uptake by oral DCs, some experimental allergen formulations have been assayed, such as conjugation with cholera toxin,13 binding to mucoadhesive agents,14 or using nanoparticles 15…”

“…Besides their better uptake, these glycoconjugates are rendered hypoallergenic16, 17, 18 and able to activate DCs to promote the induction of functional FOXP3 + Treg cells,16 thus with improved features for allergen immunotherapy 19. These properties may be especially relevant for SLIT due to the very short time the allergens are available to mucosal DCs, which might well explain the high allergen doses needed for clinical efficacy in SLIT 12, 14. Therefore, we were prompted to test the immunogenic properties of PM‐allergoids in comparison with native allergens in mice that were treated sublingually with each allergen preparation.…”

The future of immunotherapy for canine atopic dermatitis: a review

“…Adjuvanting the allergen to enhance its delivery such as packaging in VLPs prior to injection, or in a mucoadhesive polymer to prolong oromucosal contact in SLIT, is promising. [38][39][40][41] Immunomodulating substances that direct the immune system towards a Th1 cell response and/or toleranceagain as a nonspecific action that could be administered along with any specific allergen -have been studied, but principally in mouse models. 42,43 Administration of CpG oligodeoxynucleotides either as sole therapy or along with specific allergen may have benefit, including in dogs.…”

Adjuvants for allergy vaccines

“…During subcutaneous or sublingual immunotherapy, such allergen-specific CD4 + T cell responses are rather redirected toward both a Th1 type with an increased production of IFNγ (immunodeviation) as well as IL10-producing CD4 + regulatory T cells (immunosuppression). 4,19,20 Such changes in the polarization of T cell responses have been documented both in peripheral blood and in respiratory mucosae 21,22 As a consequence of such a change in the cytokine milieu, both SCIT and SLIT are associated with a decrease in seric allergen-specific IgEs, concomitantly with an upregulation of IgG1, IgG4, IgA antibodies, 4,20,23 some of which are thought to mediate a "blocking" anti-inflammatory activity. 24 Successful immunotherapy also leads to a substantial decrease in the recruitment and activation of proinflammatory cells, including basophils, mast cells and eosinophils in the skin, as well as nasal or bronchial mucosae.…”

“…The dual interest of vector systems for mucosal vaccination is (1) to enhance the duration of contact of the allergen with the mucosa, for example by using positively charged mucoadhesive polymers binding to epithelial cells, and further (2) to target efficiently phagocytic APCs by presenting the allergen in a particulate form or by interacting with a specific surface receptor expressed by dendritic cells 12,63 ( Table 2). In this regard, both nanoparticles made from polymerized maltodextrin or chitosan-based microparticles were shown to enhance the uptake of allergens by oral dendritic cells, following sublingual administration to asthmatic mice, thus resulting into a superior priming of allergen-specific Tr1 cells in draining cervical lymph nodes, and consequently in a stronger decrease in airway inflammation 23,64 ( Table 2). Still in murine models, conjugates with the outer membrane protein A from Klebsiella pneumoniae (OmpA) as well as the shiga toxin B subunit have been successfully used to target efficiently antigens/allergens to APCs [65][66][67] (Table 2).…”