Probable effective Dose Range for Allergen Extracts US Standardized Units a
Antigen
Dust mites:
D. farinae and D. pteronyssinus c
Cat d
Grass, standardized
Short ragweed f e
Non-standardized extract
-Dog g
Labeled potency or concentration a,b
3,000, 5,000, 10,000 and
30,000 AU/ml
5,000 to 10,000 BAU/ml
10,000-100,000 BAU/ml
1:10 –1:20 w/v
100,000 AU/ml
1:10- 1:100 w/v
Probable Effective Dose
Range
500-2,000 AU
1,000-4,000 BAU
1,000-4,000 BAU
6-12 mcg of Amb a 1
1000-4000 AU
Concentration of Amb a 1 is on the label of w/v extracts in FDA units f
15 mcg of Can f 1
40,000 PNU/ml a) Multiple studies have demonstrated the efficacious dose for allergen immunotherapy is between 5 mcg to 20 mcg of the major allergen per injection. Only two extracts licensed in the United States are standardized based on major allergen content (measured by radial immunodiffusion): Short ragweed (Amb a 1) and Cat (Fel d 1). b) The labeled concentrations for the non-standardized extracts have no established standards for biological potency. Non-standardized extracts are labeled on the basis of protein nitrogen unit (PNU) or the weight of the source material extracted with a given volume of extracting fluid (w/v) c) There have been no dose response studies with US licensed dust mite extracts and dosing recommendations in AU’s are extrapolated from published European studies, that used aqueous
1
and alum-precipitated extracts.
2, 3
One study designed to investigate the effect of 3 doses of an alum-precipitated D. pteronyssinus extract (0.7 mcg, 7 mcg and 21 mcg of Der p 1) found a dose response effect on efficacy and side effects.
2
The authors suggested the optimal maintenance dose was 7 mcg of Der p 1. Corresponding doses were based on specific allergen measurements of US commercially available standardized extracts provided by manufacturers. Extrapolating effective and safe doses in this manner may not be scientifically valid. D. farinae and D. pteronyssinus are similar in group 1 allergen content according to the FDA’s current reference standards.
Appropriate dose reductions would need to be made when combining antigens that have a strong degree of cross-reactivity, for example: D. pteronyssinus and D. farinae.
d) The major cat allergen Fed d 1 is reported in FDA units (Fel d 1 U) with 1 Fel d 1 U

2 to 4 mcg of Fel d 1.
4-6
The amount of Fel d 1 in 10,000 BAU/ml ranges from 10 U to
19.9 U/ml. one study demonstrated clinical efficacy of a maintenance dose of 4.56 FDA units of Fel d 1 dose in terms of decreased cat-extract PD-20, titrated skin test results and allergen specific IgE and IgG.
7, 8
In a recent study that investigated the efficacy in terms of immunological changes of 3 doses of a US licensed cat extract (0.6 mcg, 3 mcg and
15 mcg) demonstrated that a significant effect on titrated skin prick test, allergen-specific
Adapted from: Cox, L., et al., Allergen immunotherapy: A Practice Prameter Second
Update. Journal of Allergy and Clinical Immunology, 2007: p. In press. (IV).

Probable effective Dose Range for Allergen Extracts US Standardized Units a
IgG4 and CD4+/IL-4 was only seen in the group treated with 15 mcg of Fed 1, although the 3 mcg dose group did demonstrate a significant change in titrated skin test response and increase in cat specific IgG4.
9 e) There have been no dose response studies with US licensed standardized grass extracts. Recommended doses are extrapolated from published European studies that have used aqueous 10 , alum-precipitated 11, 12 and calcium phosphate- precipitated grasspollen extracts.
13
One of these studies compared a dose of 2 mcg with 20 mcg of major timothy allergen (Phl p 5 ) and found clinical efficacy at both doses.
11
The efficacy was greater in the 20 mcg of Phl p 5 dose but the systemic reaction rate was also higher in the high dose group. The package inserts for US licensed grass pollen extracts contain a table to convert the non-standardized units (w/v and PNU) for which there have been studies that have demonstrated efficacy, into BAUs. Extrapolating effective and safe doses in this manner may not be scientifically valid. Appropriate dose reductions would need to be made when combining antigens that have a strong degree of cross-reactivity, such as the
Northern pasture grasses (subfamily Pooideae ; eg, perennial rye, meadow fescue, or timothy) f) Ragweed is reported in FDA units with 1 U Amb a 1 =1 mcg of Amb a 1. The potency units for short ragweed extracts were originally assigned based on their Amb a 1 content. Subsequent data suggested that 1 unit of Amb a 1 is equivalent to 1 mcg of Amb a 1, and 350 Amb a 1 units/ml is equivalent to 100,000 BAU/ml.
14
The package insert of the Short Ragweed 100,000 AU/ml extract states the optimal immunotherapy dose is
2000 AU with a range of 1000 to 4000 AU.One open study of ragweed allergic rhinitis patients demonstrated a significant improvement in ragweed nasal challenge in patients treated with a mean dose of 6 mcg of Amb a 1 for 3 to 5 years compared with an untreated matched control group.
15
A ragweed dose response study (0.6 mcg, 12.4 mcg and 24.8 mcg Amb a 1) demonstrated efficacy as measured by nasal challenge at 12 mcg and 24 mcg Amb a 1.
16
The efficacy of the 24 mcg dose was not significantly better than the 12 mcg dose and the authors concluded that the optimal dose for ragweed extract was
> 0.6 mcg but not more than 12.4 mcg of Amb a 1. g) Dog extracts are not standardized. However, one dose response study with a US licensed acetone-precipitated dog extract investigated the efficacy of three doses (AP dog; Hollister-Stier; 0.6 mcg, 3 mcg and 15 mcg) in terms of immunological changes and found the dose of 15 mcg of Can f 1 to be most efficacious.
17 The 3 mcg dose also demonstrated significant efficacy though not as great as the 15 mcg dose. The extract used in the dosing study was assayed at 160 mcg/ml. Subsequent lots have assayed between 128-208 mcg/ml (avg Can f 1 162 mcg/ml SD+- 26mcg/ml) (Information provided by extract manufacturer Hollister-Stier)
Allergen Immunotherapy Practice Parameters 2nd Update
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Probable effective Dose Range for Allergen Extracts US Standardized Units a
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Clin Immunol 2001;107:87-93.
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16. Creticos PS, Marsh DG, Proud D, et al. Responses to ragweed-pollen nasal challenge before and after immunotherapy. J Allergy Clin Immunol 1989;84:197-205.
17. Lent A. M. HR, Sills M., Schmidt K., Efaw B. , Lebo T. , , S.; NH.
Immunological Response to Administration of Standardized
Dog Allergen Extract at Differing Doses Journal of Allergy and Clinical Immunology
2006;118: in press.
Adapted from: Cox, L., et al., Allergen immunotherapy: A Practice Prameter Second
Update. Journal of Allergy and Clinical Immunology, 2007: p. In press. (IV).