GSK Vaccines, Parc de la Noire Epine, Rue Fleming 20, 1300, Wavre, Belgium.
(at the time of study) GSK Vaccines, Rue de l'Institut 89, 1330, Rixensart, Belgium.
Reprod Toxicol. 2018 Jan;75:110-120. doi: 10.1016/j.reprotox.2017.09.006. Epub 2017 Sep 23.
The potential reproductive and developmental toxicity of the synthetic oligodeoxynucleotide (ODN) CpG 7909, a component of GSK's AS15 immunostimulant, was examined in rat and rabbit studies following intermittent intramuscular injections. Previous studies using subcutaneous and intraperitoneal injections in mice, rats and rabbits revealed that CpG ODNs induced developmental effects. To analyze the safety signal, GSK conducted additional animal studies using the intended clinical route of administration. CpG 7909 injections were administered intramuscularly to rats or rabbits 28 and 14days before pairing, on 4 or 5 occasions during gestation, and on lactation day 7. The No Observed Adverse Effect Level for female fertility, embryo-fetal and pre- and post-natal development was 4.2mg/kg in both species, approximately 500-fold higher than the anticipated human dose. In conclusion, the anticipated risk to humans is considered low for sporadic intramuscular exposure to CpG 7909.
GSK 公司的 AS15 免疫刺激剂的组成部分，合成寡脱氧核苷酸（ODN）CpG 7909，其潜在的生殖和发育毒性，在经过间歇性肌肉内注射的大鼠和兔研究中进行了检查。之前在小鼠、大鼠和兔子中使用皮下和腹腔注射的研究表明，CpG ODN 会引起发育效应。为了分析安全信号，GSK 使用预期的临床给药途径进行了额外的动物研究。CpG 7909 注射在大鼠或兔子配种前 28 天和 14 天、妊娠期间的 4 或 5 次、以及哺乳期第 7 天进行肌肉内注射。在这两种物种中，CpG 7909 对雌性生育力、胚胎-胎儿和产前及产后发育的无观察不良效应水平为 4.2mg/kg，大约是预期人类剂量的 500 倍。总之，考虑到人类偶然肌肉内接触 CpG 7909，其风险被认为较低。
