Table 4.

Mutational approaches used to produce recombinant hypoallergens (table adapted from Tscheppe et al. [113]).

Strategy	Definition	Allergen Source	Molecule/s
Fragmentation	The cDNA coding for a specific allergen is fragmented into ≥ 2 parts; the fragments may overlap or express individually	Birch pollen	Bet v 1 [115,116]
		Cow dander	Bos d 2 [117]
		Storage mite (L. destructor)	Lep d 2 [118]
		Timothy grass pollen	PhI p 1 [119]
		House dust mite (D. pteronyssinus)	Der p 2 [120]
Oligomerization	≥2 copies of the allergen-encoding cDNA are linked by oligonucleotide spacers with an open reading frame allowing the complete construct to express	Birch pollen	Bet v 1 [121]
Mosaics	The cDNA coding for a specific allergen is fragmented into several parts and the fragments are re-joined in an order different to the original sequence. If the sequence parts originate from >1 allergen the resulting protein is regarded as a hybrid mosaic	Birch pollen	Bet v 1 [122]
		Timothy grass pollen	PhI p 1 [123] PhI p 2 [124]
		Cat	Fel d 1 [125]
Chimeras/allergen hybrids	Chimeric/hybrid proteins are created by joining the genetic information of ≥2 different proteins such as constructs may contain parts or the complete original proteins	House dust mite (D. pteronyssinus)	Der p 1 [126] Der p 2 [127]
		Timothy grass pollen	PhI p 1 [128] PhI p 2 [128,129] PhI p 5 [128] PhI p 6 [129]
		Yellowjacket	Ves v 5 [130]
		Paper wasp	Pol a 5 [130]
		Honeybee	Api m 1 [131] Api m 2 [131] Api m 3 [131]
		Japanese cedar	Cry j 1 [132] Cry j 2 [132]
Point mutations	One or more nucleotide triplets coding for a specific amino acid is/are altered to replace the original amino acid at its exact position by an amino acid with different physicochemical characteristics	Birch pollen	Bet v 1 [133,134] Bet v 4 [135]
		Brassica rapa pollen	Bra r 1 [136]
		Carp	Cyp c 1 [137]
		P. Judaica pollen	Par j 1 [138]
		Gallus gallus (Ovomucoid)	Gal d 1 [114,139]
		Latex H. brasiliensis	Hev b 6.02 [140,141] Hev b 5 [142]
		House dust mite (D. pteronyssinus)	Der p 2 [143]
		Peanut	Ara h 1-3 [144,145,146]
		Ryegrass pollen	Lol p 5 [147]