甲、乙型肝炎联合疫苗接种恒河猴的初步观察

为了探索联合接种甲乙肝疫苗、实验性甲乙肝联合疫苗免疫恒河猴的安全性及免疫原性。实验中挑选了甲肝抗体阴性,乙肝两对半阴性,肝功能指标正常的健康恒河猴24只,随机分为10组。混合或分别接种,进行不同毒株的甲肝灭活疫苗与不同厂家的乙肝疫苗的配对效果比较。并接种了实验性甲乙肝联合疫苗;史克甲乙肝联合疫苗试验组。设甲肝单价灭活疫苗L8株、深圳乙肝单价疫苗作为对照。免疫方案0、4、24w。每只恒河猴接种lml。接种3d内,每天观察动物有无不良反应。接种1针和2针后4w内,每2w采集空腹静脉血,以后每4w采血1次检测抗HAV、抗HBs、ALT、AST直至40w。接种疫苗后4、8、24、28w穿刺肝组织做病理学检查。结果显示接种疫苗后3d内,所有恒河猴均无不良反应。ALT、AST无异常升高。4、8、24、28w肝组织无特殊病理改变。注射2针后4w,除3组外,其余各组抗HAV及抗HBs均阳转。3组抗HAV阳转时间迟至12w。全程免疫后12w(即40w),抗HAVGMT为258.75～37489.50mIU/ml;抗HBsGMT为8263.68～60008.064mIU/ml。甲乙肝疫苗联合免疫及实验性的甲乙肝联合疫苗接种恒河猴安全性及免疫原性均良好。

Preliminary studies on safety and efficacy of the combined vaccines of hepatitis A and hepatitis B in Rhesus monkeys

To study on the safety and efficacy of two combined vaccines of hepatitis A and hepatitis B, 24 Rhesus monkeys were randomly divided into 10 groups, 4 animals for the combined vaccine groups and 2 animals for other groups, which were anti-HAV and anti-HBV negative, with normal liver function. The Rhesus monkeys were injected 1.0ml mixed L8 or H (2) strain and HB simultaneously or SKB HAV vaccine /HBV vaccine respectively at 0, 4, 24 weeks. After injection the local and systematic reactions were observed within 3 days. Anti-HAV, anti-HBs, ALT and AST were detected in every two weeks, the same tests were performed in two weeks after second inoculation, and once every month in between 14 and 40 weeks. The liver puncture were performed at 4, 8, 24, 28 weeks for examination liver function by routine sections with H-E staining. The local and systematic reactions did not be found in all tested monkeys within three days post-vaccination, no elevation of ALT, AST and liver histopathological changes observed. The seroconversion rate of anti-HAV and anti-HBs were 100% separately, the antibody levels were 258-37489mIU/ml for HAV and 8263-60008mIU/ml for HBV. The safety and immunogenicity of both the combined vaccine and the experimental vaccine are in good quality