甲型肝炎灭活疫苗(L-A-1株)接种恒河猴的安全性及免疫原性

Safety and immunogenicity of inactivated hepatitis A vaccine(L-A-1 strain)in rhesus monkeys

目的观察甲型肝炎灭活疫苗(L-A-1株)接种恒河猴的安全性和免疫原性。方法将效价为640和1 280 EL.U/mL两个剂量的甲型肝炎灭活疫苗(L-A-1株)与进口疫苗(1 440 EL.U/mL)分别经后肢肌肉注射恒河猴,每组5只,首免后4周加强免疫1次。接种后每天观察动物接种局部有无红肿、硬结等异常反应;于免疫前、首免后1~10周定时采血,检测血清抗-甲型肝炎病毒(hepatitis A virus,HAV)抗体和丙氨酸转氨酶(alanine aminotransferase,ALT)水平;于初次免疫后第2天连续收集粪便1周,检测粪便中HAV含量;于免疫前及加强免疫后4周分别进行肝穿刺取肝组织,病理学检查。结果接种疫苗后各组恒河猴均未见异常反应;血清ALT水平未见异常升高;于首免后2周抗-HAV抗体阳转率达100%,加强免疫后血清抗-HAV抗体几何平均滴度持续升高,均在首免后7周达到峰值,随后略有下降,9~10周抗体滴度又略升高,甲型肝炎灭活疫苗(640 EL.U/mL)组抗体滴度峰值略低于甲型肝炎灭活疫苗(1 280 EL.U/mL)组和进口疫苗组,但差异无统计学意义(P>0. 05);恒河猴粪便中未检测到有HAV排出;肝组织未见病理学改变。结论甲型肝炎灭活疫苗(L-A-1株)接种恒河猴具有良好的安全性和免疫原性。

Objective To observe the safety and immunogenicity of inactivated hepatitis A vaccine(L-A-1 strain)in rhesus monkeys. Methods Fifteen rhesus monkeys were divided into three groups,five for each,and inoculated i. m. with inactivated hepatitis A vaccine(L-A-1 strain)at dosages of 640 and 1 280 EL.U/mL as well as imported vaccine at a dosage of 1 440 EL.U/mL respectively,and boosted 4 weeks later. The monkeys were observed for local reactions such as redness,swelling and duration in injection site every day,of which the serum samples were collected before and 1 ~ 10 weeks after the first immunization and determined for antibody level against hepatitis A virus(HAV)and lanine aminotransferase(ALT). The feces samples were collected starting from day 2 after the first immunization for 1 week and determined for HAV content. Liver tissues of test monkeys were collected before immunization and 4 weeks after the booster immunization for pathological examination. Results No abnormal reactions or abnormal increase of serum ALT levels were observed in monkeys of various groups after immunization. The anti-HAV antibody positive conversion rates in various groups 2 weeks after immunization were 100%,while the geometric mean titers of serum anti-HAV increased continuously after booster immunization and reached the peak value 7 weeks then decreased slightly,and increased slightly again 9 ~ 10 weeks,after the first immunization. The peak titer induced by inactivated hepatitis A vaccine at a dosage 640 EL.U/mL was slightly lower than that by the same vaccine at a dosage of 1 280 EL.U/mL and that by the imported vaccine(P > 0. 05). No HAV was detected in the feces of monkeys,and no pathological changes were observed in liver tissues. Conclusion Inactivated hepatitis A vaccine(L-A-1 strain)showed good safety and immunogenicity in rhesus monkeys.