Table 1.

Mechanisms, advantages and disadvantages of different allergen-specific immunotherapy molecules

Molecules	Mechanism	Advantages	Disadvantages
Recombinant wildtype allergens	Since B-cell and T-cell epitopes are intact, induces blocking IgGs and targets T cells	Good immunogenicity and induction of blocking IgGs	Immediate allergic reactions possible as all IgE epitopes are intact
		T-cell tolerance induction, possible	Late-phase skin reactions because of allergen-specific T-cell epitopes
Short synthetic peptides	Peptides derived from T-cell epitopes of allergens are meant to induce tolerance	No early phase reactions because of loss of IgE reactivity	No induction of allergen-specific blocking IgGs as peptides are too short
		Possible activation of regulatory T cells	Late-phase skin reactions possible because of activation of allergen specific T cells
Contiguous long overlapping peptides	Long peptides covering all linear epitopes of allergen for induction of tolerance and protective IgGs	Immunogenicity and induction of protective IgGs	Late-phase skin and pulmonary symptoms observed because of maintained allergen-specific T-cell epitopes
		No early phase reactions because of loss of three-dimensional structure	Applicable only for simple allergen sources like birch but not for complex allergen sources
Nucleic acid-based strategies	Vaccination with DNA or RNA-encoding allergens should drive immune response toward Th1	Reduced risk of inducing systemic side effects	DNA may integrate into genome
		Potential for preventive approaches	Mostly studied in animal models, only few clinical studies in humans
Recombinant hypoallergens (fragments, folding variants, mosaics, mutants)	Reduced IgE reactivity because of altered structure but maintained B-cell and T-cell epitopes for IgG induction and tolerance induction	Good immunogenicity and protective IgGs	Late-phase skin reactions because of allergen-specific T-cell epitopes
		T-cell tolerance induction, possible	Folding variants may be difficult for production
		Reduced early phase reactions because of lack of IgE reactivity
Second generation recombinant hypoallergens (peptide carrier fusion proteins)	B-cell epitopes from allergens fused to viral carrier protein for induction of blocking IgGs against allergen and against viral protein	Good immunogenicity and protective IgGs
		No late phase reactions as allergen-specific T-cell epitopes are reduced and T-cell help comes from viral carrier
		Protective against allergy and against virus that was used as a carrier
		Applicable to simple and complex allergen sources
		Suitability for preventive approaches
		No induction of IgE responses
Recombinant allergen-specific antibodies	Passive immunotherapy with recombinant high-affinity allergen specific IgGs that compete with the binding of IgE	Good effectiveness with minimal side effects	Applicable only for allergen sources with dominant major allergens like cat or birch
			Costly
			Effects not long-lasting

IgG, Immunoglobulin G.