Novel vaccines targeting dendritic cells by coupling allergoids to mannan

Abstract

Allergen-specific immunotherapy (AIT) is the single disease-modifying treatment for allergy. Clinical trials show AIT to be safe and effective for many patients; however, it still faces problems related to efficacy, safety, long treatment duration and low patient adherence. There has been intensive research to develop alternative strategies, including novel administration routes, adjuvants or hypoallergenic molecules. Promising results are reported for some of them, but clinical progress is still moderate. Allergoids conjugated to nonoxidized mannan from Saccharomyces cerevisiae have emerged as a novel concept of vaccine targeting dendritic cells (DCs). Preclinical human and animal models demonstrated that allergoids conjugated to mannan enhance allergen uptake, promote healthy responses to allergens by inducing Th1 and T regulatory (Treg) cells, and show clinical efficacy in veterinary medicine. Dose-finding phase II clinical trials in humans are currently ongoing. We review the current stage of allergoids conjugated to mannan as next generation vaccines for AIT.

Carbohydrate Conjugates in Vaccine Developments

“…Allergen-specific immunotherapy has attracted researchers' attention as it may provide a long-lasting relief from allergy for the patients. Mannan-allergen conjugates have been studied as potential anti-allergy vaccines (Benito-Villalvilla et al, 2018).…”

Innate immunity in allergy

“…These vaccines are candidates for AIT of allergic diseases as they promote the generation of Treg cells by mechanisms partially depending on programmed death‐ligand 1 (PD‐1) and IL‐10 in both humans and mice . Phase II clinical trials for grass‐pollen and house dust mite allergens are currently ongoing …”

Mast cells and γδ T cells are largely dispensable for adaptive immune responses after laser-mediated epicutaneous immunization

“…Unlike laser microporation, this technique has to be rated as much less invasive. Also the tape-stripped skin area is inevitably larger compared to the constrained area of 10 mm 2 treated with the laser, on which the (epi)dermal tissue between the micropores is left intact [16]. In the above mentioned work, communication between epithelial cells and DETCs via the activating receptor NKG2D was crucial for induction of TH2-biased responses.…”

“…As pattern recognition receptors (PRRs), CLRs play various roles in eliciting immune responses depending on the detected pathogen-associated molecular pattern (PAMP). The potential of the carbohydrate mannan as an adjuvant capable of enhancing and shaping the overall immune response has been demonstrated to rely on its capacity to engage CLRs [16, 17]. We have previously reported that EPI with allergen-mannan neoglycoconjuates by laser microporation leads to more efficient antigen uptake by dDCs and LCs.…”