中国药物警戒 ›› 2018, Vol. 15 ›› Issue (3): 132-135.

• 基础与临床研究 • 上一篇    下一篇

食蟹猴肌内注射重组乙型肝炎疫苗重复给药毒性实验研究

李萌1, 戴晓莉2, 戴学栋2, 马玉奎2   

  1. 1 青岛市中心医院药学部，山东 青岛 266042；
    2 山东省药学科学院，山东 济南 250100
  • 收稿日期:2017-12-04 修回日期:2018-05-04 出版日期:2018-03-20 发布日期:2018-05-04
  • 通讯作者: 马玉奎，男，博士，主任药师，新药安全性评价。 E-mail：yukuima@sina.com
  • 作者简介:李萌，男，硕士，副主任药师，临床药理学。
  • 基金资助:
    山东省创新公共服务平台项目（2015CXPT00001）：山东抗体类和疫苗类生物药物临床前评价公共服务平台的完善与运行。

Intramuscular Repeated Dose Toxicity of Recombinant Hepatitis B Vaccine in Cynomolgus Monkeys

LI Meng1, DAI Xiao-li2, DAI Xue-dong2, MA Yu-kui2   

  1. 1 Qingdao Central Hospital,Shandong Qingdao 266042, China;
    2 Shandong Academy of Pharmaceutical Sciences, Shandong Jinan 250100, China
  • Received:2017-12-04 Revised:2018-05-04 Online:2018-03-20 Published:2018-05-04

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摘要： 目的 研究重复肌内注射给予重组乙型肝炎疫苗4次对食蟹猴产生的毒性。方法 正常食蟹猴30只，分为重组乙型肝炎疫苗20、40 μg/只两个剂量组和空白对照组，每组肌内注射接种相应剂量的药物，每2周接种1次，共4次，末次接种后停药恢复15天。通过检测体重、心电、体温、眼科、尿液、血液学、血液生化学、免疫指标以及脏器相对重量和组织病理学，全面评价其对食蟹猴的毒性作用。结果 重组乙型肝炎疫苗40 μg/只剂量下轻微抑制食蟹猴体重增长和 NE%、EO%等血液学指标升高，对注射部位有轻微刺激作用，20和40 μg/只接种2次后可诱导食蟹猴产生高水平的抗体，对其他指标无明显影响。结论 食蟹猴肌内注射≥20μg/只重组乙型肝炎疫苗4次对食蟹猴有较强的免疫原性，40μg/只对体重增长、血液学和注射部位有轻微影响，无其他毒性反应。

关键词: 重组乙型肝炎疫苗, 毒性, 免疫原性, 食蟹猴

Abstract: Objective To study the intramuscular repeated dose toxicity of recombinant hepatitis B vaccine in cynomolgus monkeys. Methods Thirty normal cynomolgus monkeys were divided into three groups：normal control group and recombinant hepatitis B vaccine groups (20, 40 μg, each animal). The cynomolgus monkeys were administered intramuscularly with corresponding dose of drug for four times and followed with four weeks withdrawal. The body weight, body temperature, ECG, ophthalmology, urine, hematology, blood biochemistry, immune indexes, viscera index and histopathology were examined to study the toxicity of recombinant hepatitis B vaccine in cynomolgus monkeys. Results The body weight gain of normal cynomolgus monkeys were slightly reduced after administration with recombinant hepatitis B vaccine (40 μg, each animal). Abnormal increase of the levels of NE%、EO% and slight muscle stimulation were also found after administration. High level of antibody was induced after administration with recombinant hepatitis B vaccine (20, 40 μg, each animal) for two times. Conclusion Recombinant hepatitis B vaccine intramuscularly taken showed significant immunogenicity(20, 40 μg, each animal) and there were slight toxicities on body weight, hematology and injection site after administration with recombinant hepatitis B vaccine (40 μg, each animal).

Key words: recombinant hepatitis B vaccine, toxicity, immunogenicity, cynomolgus monkey

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