Turkeltaub P C, Campbell G, Mosimann J E
Laboratory of Allergenic Products, Food and Drug Administration, Bethesda.
Allergy. 1990 Oct;45(7):528-46. doi: 10.1111/j.1398-9995.1990.tb00529.x.
One high potency (HP) and two low potency (LP) commercial whole short ragweed (WSR) extracts were assayed for relative potency (RP) by antigen E (AgE-Amb a 1), RAST inhibition, and parallel line bioassay (PLBA). The RP of the HP extract (300 micrograms AgE) was equal to the reference WSR, but the LP extracts were only approximately 0.01 of the RP of the reference. Each extract was administered to fall hay fever patients with skin sensitivity to WSR (less than or equal to 10(-3) micrograms/ml AgE for sum of erythema = 50 mm) to the maximum tolerated dose, or 0.5 cc of the concentrate, by either a 9- or 40-dose regimen. HP-treated patients had significantly lower symptom scores than untreated controls. No significant difference was noted in the total symptom scores between HP and LP extract-treated patients. Despite approximately 100-fold differences in the RP of HP versus LP extracts, both produced similar frequencies of severe systemic and severe late phase local reactions. Furthermore, when RP of HP and LP extracts were estimated by PLBA, both reached similar peak dosages, similar dosage for IgG WSR antibody response, and comparable IgG WSR antibody levels, indicating that the WSR dose estimates based on RP were bioequivalent. The 9-dose HP regimen produced fewer late phase local and systemic reactions per patient than the 40-dose HP regimen. Most patients experiencing severe systemic reactions were among those most skin sensitive to WSR. The number of systemic reactions per injection was significantly higher at higher WSR doses. One LP extract produced a high incidence of systemic reactions in the initial three injections. With respect to HP, its RP varied approximately 10-fold depending on the skin sensitivity of the patient to heat-stable ragweed allergens, demonstrating that it was compositionally different. However, when the dose of this extract was estimated by RP based on the skin sensitivity of each patient, the peak dose of the extract as well as the doses associated with late phase and systemic reactions were found to be similar to the HP doses. This indicated that immunizing dose estimates of compositionally different WSR extracts based on RP by PLBA were also bioequivalent.
通过抗原E（AgE - Amb a 1）、放射性变应原吸附试验（RAST）抑制和平行线生物测定法（PLBA），对一种高效力（HP）和两种低效力（LP）的市售全株短豚草（WSR）提取物进行了相对效力（RP）测定。高效力提取物（300微克AgE）的RP与参考WSR相等，但低效力提取物的RP仅约为参考物的0.01。将每种提取物给予对WSR皮肤敏感的秋季花粉症患者（红斑总和为50毫米时，对AgE的敏感度小于或等于10⁻³微克/毫升），采用9剂量或40剂量方案，给予最大耐受剂量或0.5毫升浓缩物。接受高效力提取物治疗的患者症状评分显著低于未治疗的对照组。高效力和低效力提取物治疗的患者总症状评分无显著差异。尽管高效力提取物与低效力提取物的RP相差约100倍，但两者产生严重全身反应和严重迟发性局部反应的频率相似。此外，当通过PLBA估计高效力和低效力提取物的RP时，两者达到相似的峰值剂量、相似的IgG WSR抗体反应剂量以及相当的IgG WSR抗体水平，这表明基于RP的WSR剂量估计在生物等效性上是相同的。9剂量的高效力提取物方案比40剂量的高效力提取物方案每位患者产生的迟发性局部和全身反应更少。大多数经历严重全身反应的患者是那些对WSR皮肤最敏感的患者。在较高的WSR剂量下，每次注射的全身反应数量显著更高。一种低效力提取物在最初三次注射中产生全身反应的发生率较高。关于高效力提取物，其RP根据患者对热稳定豚草过敏原的皮肤敏感度变化约10倍，表明其成分不同。然而，当根据每位患者的皮肤敏感度通过RP估计该提取物的剂量时，发现该提取物的峰值剂量以及与迟发性和全身反应相关的剂量与高效力提取物的剂量相似。这表明通过PLBA基于RP对成分不同的WSR提取物进行免疫剂量估计在生物等效性上也是相同的。
