甲肝灭活疫苗接种安全性及免疫效果观察

Study on Safety and Effecacy of Inactivated Hepatitis A Vaccine in Rhesus Monkey

目的 观察甲型肝炎灭活疫苗的安全性及免疫效果。方法 挑选甲肝抗体阴性、丙氨酸转氨酶 (ALT)正常的健康的恒河猴 10只。随机分为 5组 ,每组 2只 ,每只接种 1ml甲肝疫苗 ,分别接种甲肝灭活疫苗吕 8株 (Lu8)、H2 株及史克疫苗。方案 :0、4周接种。接种 3天内 ,每天观察有无局部及全身反应。首次注射后每周采静脉血 1次 ,加强 1针后每 2周采血 1次检测抗HAV及ALT ,14周后改为每 4周采血 1次直至 4 6周。每周采粪便 2次 ,连采 4周 ,用KMB17细胞进行病毒分离。 4、8周肝组织穿刺作病理学检查。结果 接种疫苗后 3天内 ,所有猴子均无局部及全身反应。ALT正常 ,4、8周肝脏穿刺无特殊组织病理改变。首次注射后 2周 10 0 %抗体阳转 ,4周效价为 374 8mIU/ml～ 937mIU/ml。加强 1针后抗HAV效价有 10倍以上升高 ,抗体最高达 14 992mIU/ml,到 4 6周抗体水平持续在 2998 4mIU/ml～ 74 96mIU/ml之间 ,GMT为 31 2～ 34 2。大便传代 2次无排毒。结论 4批国产甲肝灭活疫苗接种恒河猴具有很好的安全性和可靠的免疫效果。

Objective To study on the safety and efficacy of inactivated hepatitis A vaccine in rhesus monkeys.Methods Ten rhesus monkeys with negative anti-HAV and normal liver function were divided randomly into 5 groups.Two animals for 1 specimen,1ml specimen of Lu8,H\-2 strain and SKB vaccines were injected by IM into rhesus respectively at 0th?4th week.The local and body reaction were observed within 3 day after injection.The blood test for anti-HAV and ALT were detected at once every week.The same test did once every two weeks after second inoculation,and once every month within 14th-46th weeks.HAV was isolated and identified by KMB17 cells/EIA from feces collected at twice in 1-4weeks postinoculation.Liver puncture was performed at 46th week for examing liver histopathology by routine sections with H-E staining.Results Local and body reaction was not observed in all rhesus monkey within 3 day after vacination,no elevation of ALT and liver histopathological change in all rhesus monkeys.Tbe seroconversion rate of anti-HAV was 100% at second week after first inoculation.The valence of antibody was 374.8-937mIU/ml at 4th week.The titer of antibody got up >10 fold after booster inoculation,and kept 2 998.4 mIU/ml-7 496mIU/ml at 46th weeks.GMTs were 31.2-34.2.Two passages of feces were negative for HAV.Conclusion Four batchs of inactivated HAV vaccines has good effectiveness and safety.