甲型肝炎灭活疫苗不同免疫方案对恒河猴免疫效果观察

Studies on vaccination schedule of inactivated hepatitis A vaccine

目的 确定甲型肝炎灭活疫苗免疫恒河猴最佳免疫方案。方法 根据 3个免疫方案(方案 1:0周免疫 ;方案 2 :0周初次免疫、4周加强免疫 ;方案 3:0周初次免疫、2 4周加强免疫 ) ,将 17只抗 HAV阴性的恒河猴随机分成 4组 ;第 1组 :免疫方案 1;第 2组 :免疫方案 2 ;第 3组 :免疫方案 3。1～ 3组各 5只 ,空白对照组 2只。用同等剂量 (12 80EL .U/ml)的甲型肝炎灭活疫苗于上臂三角肌内分别免疫两组恒河猴 ,检测恒河猴谷丙转胺酶 (ALT)水平、肝脏病理、抗 HAV水平。结果 3组猴在5 2周观察期内未出现肝脏病理改变及ALT水平异常升高。方案 1组猴IgG水平在 12周达最高水平(132 19mIU/ml) ,随后逐渐下降 ,第 5 2周降为 2 0 5 6mIU/ml。方案 2组在 4周加强后 ,第 12周达最高水平为 1386 3mIU/ml,第 5 2周降为 6 2 85mIU/ml。方案 3组在第 2 4周加强免疫后 ,第 2 8周抗 HAV水平明显提高 ,达到最高水平 ,为 40 6 38mIU/ml。结论 甲型肝炎灭活疫苗 (吕 8株 )具良好的安全性和免疫原性 ;0周初次免疫、2 4周加强免疫方案具最佳免疫效果。

Objective To evaluate three vaccination schedules of inactivated hepatitis A vaccine in rhesus monkeys (Macaca Mulatta) . Methods Seventeen rhesus monkeys were divided randomly into four groups. The first group of five monkeys was immunized with vaccination schedule 1 (one immunization at week 0); The second group of five monkeys was immunized with vaccination schedule 2 ( first injection at week 0, and booster one at week 4); the third group of five monkeys was immunized with vaccination schedule 3 (first injection at week 0, and booster one at week 24); and the fourth group of two monkeys with MEM as control. Rhesus monkeys were inoculated by intramuscular injections to detect the ALT (alanine aminotransferase), liver pathology and anti HAV at different time. Results During the 52 week observation, no abnormal elevation of ALT or liver pathology appeared . The IgG response for vaccination schedule 1 reached the highest level (13 219 mIU/ml), and decreased gradually to 2 056 mIU/ml at week 52. After booster immunization at week 4, the IgG response for vaccination schedule 2 was 13 863 mIU/ml at week 12, and decreased to 6 285 mIU/ml. The highest level of IgG (40 638 mIU/ml) for vaccination schedule 3 appeared at week 28 after booster injection at week 24. Further more, at week 52 the IgG level for vaccination schedule 3 was also the highest among the three vaccination schedules. Conclusions The inactivated hepatitis A vaccine is safe and well immunogenic. The vaccination schedule 3 showed the best immune response among the three vaccination schedules.