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首页> 外文期刊>Journal of applied toxicology >A safety study of a B class CpG ODN in Sprague-Dawley rats
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A safety study of a B class CpG ODN in Sprague-Dawley rats

机译：Sprague-Dawley大鼠B类CpG Odn的安全研究

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ABSTRACT: Oligodeoxynucleotides containing CpG motifs (CpG ODNs) are potent immune activators and are being tested as anti-tumor, antimicrobial agents and as adjuvants in vaccines. Little has been reported, however, about the systematic and comprehensive safety evaluation on repeated CpG ODN administration. To investigate the safety profile of a newly developed CpG ODN, CpG 684, we conducted a 28-day repeated dose toxicity study in rats, at dose levels of 5,20 and 150 ug CpG 684 per rat. No abnormalities in clinical observations, growth, urinalysis and bone marrow cell counts were found in CpG 684 treated rats. CpG 684 was proved biologically active, capable of up-regulating the expressions of CD40 and CD86 molecules. The monocyte numbers were increased at the dose levels of 20 and 150mug per rat. The spleen weights were increased in female rats at the dose level of 150mug per rat. Microscopically, 5, 20 and 150mug per rat CpG 684 caused local inflammatory cell infiltration and hyperplasia of fibrous tissue at injection sites; the treatment of 5 and 150mug per rat CpG 684 induced enhanced inflammatory reaction in inguinal lymphoid tissue, and the dose of 150mug per rat induced cell hyperplasia in white pulp of spleen and white pulp expansion. CpG 684 at 150 ug per rat led to decreases in peripheral lymphocyte, serum globulin, glucose, alkaline phosphatase and K~+ levels in female rats, and induced the decrease in serum albumin and total protein in rats of both sexes. The data from this study will provide an important reference for developing CpG 684 as an adjuvant for vaccines of human use.
机译：摘要：含有CpG基序（CpG ODN）的寡聚寡核苷酸是有效的免疫活化剂，并在抗肿瘤，抗微生物剂和疫苗中作为佐剂进行测试。然而，据报道，关于重复的CPG ODN管理的系统和全面的安全评估。为了调查新开发的CPG ODN，CPG 684的安全性曲线，我们在大鼠中进行了28天的重复剂量毒性研究，剂量水平为5,20和150μg/大CPG 684。在CPG 684处理的大鼠中发现了临床观察，生长，尿症和骨髓细胞计数的异常。 CPG 684被证明是生物活性的，能够上调CD40和CD86分子的表达。单核细胞数在每鼠20和150mug的剂量水平时增加。在每鼠150mug的剂量水平的雌性大鼠中脾脏重量增加。每大鼠的显微镜，5,20和150mug，导致注射部位的局部炎症细胞浸润和纤维组织的增生;每大鼠CPG 684治疗5和150Mug诱导脾脏淋巴组织中增强的炎症反应，每大鼠脾脏白色纸浆白色纸浆中每个大鼠诱导细胞增生剂的剂量。每个大鼠150μg的CpG 684导致雌性大鼠外周血淋巴细胞，血清淋巴细胞素，血糖，碱性磷酸酶和K〜+水平降低，并诱导两性大鼠血清白蛋白和总蛋白质的降低。本研究的数据将为开发CPG 684作为人类使用疫苗的佐剂提供重要参考。

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