Trivedi Bhavini, Valerio Cherry, Slater Jay E
National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md, USA.
J Allergy Clin Immunol. 2003 Apr;111(4):777-83. doi: 10.1067/mai.2003.1338.
Endotoxin is a ubiquitous and potent proinflammatory agent. Previous limited studies suggest that it is pres-ent in allergen vaccines and that this could affect the safety and efficacy of allergen immunotherapy. The endotoxin content of standardized allergen vaccines is unknown.
The purpose of this study was to quantify the amount of endotoxin contained in standardized allergen vaccines.
The endotoxin content of 14 allergen vaccines was measured by using the Limulus amebocyte lysate (LAL) gel-clot assay. To account for (1,3)-beta-d-glucan and protease interference, vaccines were selectively depleted of endotoxin and then retested with the gel-clot assay. Proteases were also heat-inactivated in selected vaccines. Fifty-eight lots of vaccines were tested, including at least two manufacturers per vaccine.
The endotoxin content of the 58 vaccines ranged from undetectable to 34,000 EU/mL. Cat pelt (12,735 EU/mL; range, 5177 to 33,805) had significantly more endotoxin activity than cat hair (2883 EU/mL; range, 1 to 16,962), and Dermatophagoides farinae extracts (4619 EU/mL; range, 849 to 8485) had more than Dermatophagoides pteronyssinus (11 EU/mL; range, 1 to 34). Grass (160 EU/mL; range, 3 to 1561) and ragweed pollen (341 EU/mL; range, 8 to 1697) vaccines contained less endotoxin. (1,3)-beta-d-glucan interference was significant (>10%) only in three ragweed vaccines and two grass vaccines. Heat inactivation had no effect. There were considerable differences in endotoxin content of the same vaccines made by different manufacturers.
The endotoxin content of standardized allergen vaccines is extremely variable. Interference by proteases and (1,3)-beta-d-glucans is minimal. The effects of the high levels of endotoxin in some vaccines on the immunomodulatory changes associated with allergen immunotherapy require further study.
内毒素是一种普遍存在且强效的促炎剂。先前的有限研究表明，它存在于变应原疫苗中，这可能会影响变应原免疫疗法的安全性和有效性。标准化变应原疫苗的内毒素含量尚不清楚。
本研究的目的是量化标准化变应原疫苗中所含内毒素的量。
使用鲎试剂凝胶凝固法测量14种变应原疫苗的内毒素含量。为了排除（1,3）-β-d-葡聚糖和蛋白酶的干扰，对疫苗进行选择性内毒素去除，然后用凝胶凝固法重新检测。还对选定的疫苗进行蛋白酶热灭活处理。共检测了58批疫苗，每种疫苗至少检测两个制造商的产品。
58种疫苗的内毒素含量范围从检测不到到34,000 EU/mL。猫皮（12,735 EU/mL；范围为5177至33,805）的内毒素活性显著高于猫毛（2883 EU/mL；范围为1至16,962），粉尘螨提取物（4619 EU/mL；范围为849至8485）的内毒素含量高于屋尘螨（11 EU/mL；范围为1至34）。草（160 EU/mL；范围为3至1561）和豚草花粉（341 EU/mL；范围为8至1697）疫苗的内毒素含量较低。仅在3种豚草疫苗和2种草疫苗中存在显著的（1,3）-β-d-葡聚糖干扰（>10%）。热灭活没有效果。不同制造商生产的相同疫苗的内毒素含量存在相当大的差异。
标准化变应原疫苗的内毒素含量变化极大。蛋白酶和（1,3）-β-d-葡聚糖的干扰极小。某些疫苗中高水平内毒素对与变应原免疫疗法相关的免疫调节变化的影响需要进一步研究。
