Table 1 Novel vaccine development for allergen-SIT
Type of the vaccine/approach | Description and mechanism | Current status |
|---|---|---|
Bypassing IgE and targeting T cells | ||
Major allergens or their fragments are fused and expressed as a single recombinant protein. IgE binding is attenuated, T cell reactivity is preserved. Preventive effect on generation of IgE is demonstrated in mice. | Effects in human cell cultures and mouse models. | |
Hypoallergenic hybrid molecules [5] | Derived from Der p 1 and Der p 2, reduced IgE reactivity of hybrid proteins, induce higher T cell proliferation responses. | Effects in human cell cultures and mouse models. |
Fragments of major allergens [6] | Major allergen (Bet v 1) is divided into nonIgE binding fragments. IgE binding is attenuated and T cell reactivity is preserved. | A multi center clinical trial has been finalized. |
NonIgE binding T cell epitope peptides (Fel d 1, Api m 1) have been used in cat and bee venom allergy. | Several promising clinical studies have been performed. Safe and tolerable in cat allergics | |
Unrefolded native or recombinant allergens [12] | Major recombinant allergens (Api m 1, Bet v 1) are not refolded to the native conformation. This decreases or abolishes IgE binding, but preserves T cell reactivity. | Several studies reported promising results. |
Polymers of major allergens [6] | Major allergen (Bet v 1) is trimerized. Mast cell, basophil degranulation is attenuated, T cell reactivity is preserved in vitro. | A multi center clinical trial has been finalized. |
Reconstitution of the natural extract with multiple recombinant allergens | ||
Mixture of several major recombinant allergens [13] | A mixture of five recombinant grass pollen allergens (Phl p 1, Phl p 2, Phl p 5a, Phl p 5b, Phl p 6) reduced symptoms and need for symptomatic medication in grass pollen allergic patients. | One clinical trial reported promising results. |
Allergens coupled to adjuvants | ||
GpG oligonucleotide-conjugated allergens [14] | Major allergen (Amb a 1) is bound to a toll-like receptor 9-triggering CpG oligonucleotide. | A large multicenter clinical trial did not reach endpoints, but the clinical efficacy was robustly demonstrated. |
Allergens coupled to virus-like particles [15] | Der p 1 coupled to highly repetitive virus capside-like recombinant particles | Rapid induction of high IgG antibody titers was observed in healthy human volunteers. |
Carbohydrate-based particles [16] | Carbohydrate-based particles-bound rPhl p 5b induced a stronger antibody and cytokine responses. | In murine models. |
Hypoallergenic vaccine based on allergen-derived peptides fused to hepatitis B PreS [17] | Recombinant fusion proteins show reduced allergenic activity in basophil activation and no IgE reactivity. | In murine models. |
Monophosphoryl lipid A (MPL) formulated with allergoid [18] | Pollen allergoid formulated with the Th1-inducing adjuvant monophosphoryl lipid A (MPL) facilitates short-term SIT. | Results of clinical trials have been reported. |
Novel routes of administration | ||
Intralymphatic vaccination [19] | Allergen-SIT vaccines administered directly into a lymph node. The aim is to deliver high amounts of allergens into secondary lymphatic organs. | Results of a clinical trial have been reported to show safety and efficacy. |
Epicutaneous vaccination [20] | High numbers of antigen presenting cells (LCs), non-vascularized area, safe, needle-free, and potentially self-administrable. | Clinical trial in grass pollen-induced rhinoconjunctivitis demonstrated safety and efficacy. |
Fusion with immune response modifiers | ||
Fusion of allergens with human Fcγ has been reported to inhibit allergen-induced basophil and mast cell degranulation by crosslinking Fcγ and FcϵRI receptors. | Human cell cultures and mouse models. | |
Modular antigen translocation (MAT) vaccines [23] | The fusion of transactivator of transcription (Tat) peptide to both truncated invariant chain and allergens is able to target antigens to the nascent MHC II molecules in the trans-golgi compartment. | Clinical trial is finalized and demonstrated safety and efficacy with evidence of immune regulation. |
Combined treatment with immune response modifiers | ||
To reduce SIT induced side effects. To enable relatively rapid dose increase To use relatively high doses | Significantly fewer systemic allergic reactions, more patients were able to reach the target maintenance immunotherapy dose. | |