【摘要】：目的:評價大鼠重復給藥預防宮頸癌的HPV疫苗的安全性。方法:將大鼠按體重隨機分為4組:陰性對照組、鋁佐劑對照組,HPV疫苗低劑量組和高劑量組,分別在d 1,d 22,d 43,d 64肌內注射給藥,恢復期4周,于給藥前和給藥后不同時間點進行各項毒理學指標檢測。結果:各組動物的臨床癥狀、體重、攝食量、體溫、和尿檢查各項指標均未見與給藥相關的明顯異常。在末次給藥結束后,HPV給藥組動物血液中性粒細胞及白細胞數(shù)量輕微升高,但在停藥4周后恢復正常。抗核抗體檢測結果顯示各組動物各時間點血清均為陰性。疫苗所含3種抗原蛋白在大鼠體內均能誘導產(chǎn)生較高的抗體滴度,表明疫苗具有良好的免疫原性。組織病理學檢查結果顯示與給予供試品相關的病理學變化主要發(fā)生于注射部位、坐骨神經(jīng)、肌肉(骨骼肌)以及腹股溝淋巴結,表現(xiàn)為不同程度的肉芽腫性炎癥、間質纖維組織增生、水腫、炎性細胞浸潤等,停藥后逐漸減輕。結論:大鼠重復肌內注射HPV疫苗,具有良好的耐受性,無明顯毒性反應劑量為人用劑量的2倍。本研究為下一步HPV疫苗進入臨床試驗奠定了基礎。
[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.
【作者單位】： 中國食品藥品檢定研究院國家藥物安全評價監(jiān)測中心藥物非臨床安全評價研究北京市重點實驗室;北京康樂衛(wèi)士生物技術股份有限公司;
【基金】：國家“重大新藥創(chuàng)制”科技重大專項資助項目(2015ZX09501007-004)
【分類號】：R392-33
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本文編號：2317013