Wistar大鼠肌内注射HPV疫苗重复给药毒性研究
发布时间：2018-11-07 17:10
【摘要】：目的:评价大鼠重复给药预防宫颈癌的HPV疫苗的安全性。方法:将大鼠按体重随机分为4组:阴性对照组、铝佐剂对照组,HPV疫苗低剂量组和高剂量组,分别在d 1,d 22,d 43,d 64肌内注射给药,恢复期4周,于给药前和给药后不同时间点进行各项毒理学指标检测。结果:各组动物的临床症状、体重、摄食量、体温、和尿检查各项指标均未见与给药相关的明显异常。在末次给药结束后,HPV给药组动物血液中性粒细胞及白细胞数量轻微升高,但在停药4周后恢复正常。抗核抗体检测结果显示各组动物各时间点血清均为阴性。疫苗所含3种抗原蛋白在大鼠体内均能诱导产生较高的抗体滴度,表明疫苗具有良好的免疫原性。组织病理学检查结果显示与给予供试品相关的病理学变化主要发生于注射部位、坐骨神经、肌肉(骨骼肌)以及腹股沟淋巴结,表现为不同程度的肉芽肿性炎症、间质纤维组织增生、水肿、炎性细胞浸润等,停药后逐渐减轻。结论:大鼠重复肌内注射HPV疫苗,具有良好的耐受性,无明显毒性反应剂量为人用剂量的2倍。本研究为下一步HPV疫苗进入临床试验奠定了基础。
[Abstract]:Objective: to evaluate the safety of repeated administration of HPV vaccine against cervical cancer in rats. Methods: rats were randomly divided into 4 groups according to their body weight: negative control group, aluminum adjuvant control group, low dose HPV vaccine group and high dose group. The toxicological indexes were detected before and after administration. Results: the clinical symptoms, body weight, food intake, body temperature and urine examination of the animals in each group were not significantly abnormal related to drug administration. At the end of the last administration, the neutrophil and leukocyte count in HPV group increased slightly, but returned to normal 4 weeks after withdrawal. The results of antinuclear antibody test showed that the serum of each group was negative at each time point. The three antigenic proteins contained in the vaccine could induce high antibody titers in rats, which indicated that the vaccine had good immunogenicity. Histopathological findings showed that the histopathological changes associated with the administration of the sample mainly occurred at the injection site, sciatic nerve, muscle (skeletal muscle) and inguinal lymph nodes, with varying degrees of granulomatous inflammation. Interstitial fibrous tissue proliferation, edema, inflammatory cell infiltration and so on, gradually alleviated after withdrawal. Conclusion: repeated intramuscular injection of HPV vaccine in rats has good tolerance, and the dose of no obvious toxic reaction is twice as high as that of human dose. This study laid a foundation for further clinical trials of HPV vaccine.
【作者单位】： 中国食品药品检定研究院国家药物安全评价监测中心药物非临床安全评价研究北京市重点实验室;北京康乐卫士生物技术股份有限公司;
【基金】：国家“重大新药创制”科技重大专项资助项目(2015ZX09501007-004)
【分类号】：R392-33
，
本文编号：2317013
[Abstract]:Objective: to evaluate the safety of repeated administration of HPV vaccine against cervical cancer in rats. Methods: rats were randomly divided into 4 groups according to their body weight: negative control group, aluminum adjuvant control group, low dose HPV vaccine group and high dose group. The toxicological indexes were detected before and after administration. Results: the clinical symptoms, body weight, food intake, body temperature and urine examination of the animals in each group were not significantly abnormal related to drug administration. At the end of the last administration, the neutrophil and leukocyte count in HPV group increased slightly, but returned to normal 4 weeks after withdrawal. The results of antinuclear antibody test showed that the serum of each group was negative at each time point. The three antigenic proteins contained in the vaccine could induce high antibody titers in rats, which indicated that the vaccine had good immunogenicity. Histopathological findings showed that the histopathological changes associated with the administration of the sample mainly occurred at the injection site, sciatic nerve, muscle (skeletal muscle) and inguinal lymph nodes, with varying degrees of granulomatous inflammation. Interstitial fibrous tissue proliferation, edema, inflammatory cell infiltration and so on, gradually alleviated after withdrawal. Conclusion: repeated intramuscular injection of HPV vaccine in rats has good tolerance, and the dose of no obvious toxic reaction is twice as high as that of human dose. This study laid a foundation for further clinical trials of HPV vaccine.
【作者单位】： 中国食品药品检定研究院国家药物安全评价监测中心药物非临床安全评价研究北京市重点实验室;北京康乐卫士生物技术股份有限公司;
【基金】：国家“重大新药创制”科技重大专项资助项目(2015ZX09501007-004)
【分类号】：R392-33
，
本文编号：2317013
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