Table 2. Strategies for improving specific immunotherapy.

	Strategies	Examples	References
Molecule-based
Natural molecules	Chemical treatment of extracts	Depigmented aldehyde-treated extracts (house dust mite, grass and tree pollen)	[17–24]
Synthetic molecules	Peptides	T-cell peptides of Fel d 1	[15▪]
Recombinant molecules	Folding variants	Pru p 3 folding variant	[27]
	Mutants	Mus m 1 structural mutant	[28]
	Fragments/oligomers	Art v 1 mutation of disulfide bonds	[29]
	Hybrids	Trimer of Bet v 1 fragment	[30]
		Fel d 1 with duplicated T-cell epitopes and disrupting of disulfide bonds	[31]
		Feld 1 random mutations	[34]
		Der p 1–2 hybrid	[33]
	Peptide-carrier fusion proteins	Ole e 1 peptides coupled to KLH	[39]
		Der p 2 peptides coupled to KLH	[40]
		Alt a 1 peptides coupled to KLH	[41]
		Phl p 1 peptides fused to VP1	[43]
		Fel d 1 peptides fused to PreS	[44▪]
	DNA vaccines	Der p 2 mutant	[47]
		Der p 1 mature	[48]
		Cyn d 1	[49]
	RNA vaccines		[50]
Routes
Oral	Desensitization in food allergy	Peanut flour	[52]
	Edible seeds	Rice seeds with shuffled Cry j 2,Der p 1 fragment, Der f 2 with disrupted disulfide bonds [57]	[54–56]
Sublingual	Recombinant allergens	Natural-like recDer p 2	[58]
Epicutaneaous	Pollen extract patches	Grass pollen extract	[60]
	Food allergens	Peanut extract	[61]
Intralymphatic	MAT	MAT-Fel d 1	[62▪]
Immunomodulation
Conjugated molecules	CpGs	Cry j 1-CpG	[64]
	Vitamin D3	Fel d 1 Vit D3	[66]

KLH, keyhole limpet hemocyanin; MAT, modular antigen transporter.