目的 評價重組三價人乳頭瘤病毒（HPV）疫苗的急性毒性。方法 將Wistar大鼠隨機分成2組：陰性對照組和HPV疫苗組，每組20只，HPV疫苗組單次sc 3倍人用劑量（1.5 mL）HPV疫苗，陰性對照組注射等體積的生理鹽水。觀察動物臨床狀態(tài)；檢測動物體質量變化；給藥后第15天，解剖大鼠，進行大體病理學檢查。結果 動物單次給藥大劑量HPV疫苗后，臨床癥狀均未見明顯異常；與對照組比較，給藥組動物體質量增長未見顯著性差異；病理學檢查未見與供試品相關的明顯異常。結論 Wistar大鼠單次sc重組三價HPV疫苗總體耐受性良好，未見明顯毒性反應，為進一步臨床前評價HPV疫苗的安全性奠定了基礎。

objective To evaluate the acute toxicity of recombinant trivalent human papillomavirus (HPV) vaccines.Methods Wistar rats were randomly divided into negative control and HPV groups with 20 rats in each group. Rats in HPV groups were sc administered with a single-dose of 1.5 mL of HPV vaccines (three times of human dose/each rat), while rats in negative control group were given equal volume of saline. The clinical state of animals was observed, and the body mass changes were detected. Rats were dissected after 15 d of treatment and examined by gross pathology.Results Following a single injection with high-dose HPV vaccines, there were not obvious abnormalities in clinical symptom. Compared with negative control group, the body weight of rats from HPV vaccines-treated group had no significant difference. No obvious macro-pathological change was found in all animals.Conclusion Single sc injection with recombinant trivalent HPV vaccines is well tolerated and no obvious toxicological change is found in Wistar rats. These results will facilitate further preclinical safety studies of HPV vaccines.

“重大新藥創(chuàng)制”科技重大專項（2015ZX09501007-004）