流行性出血热(EHF)Ⅱ型(家鼠型)纯化灭活疫苗Ⅰ期临床观察

Observations On clinical trial of type Ⅱ purified Epidemic Haemorrhagic fever (EHF) Vaccine

根据卫生部(91)特申体第02号文,92年完成了Ⅱ型纯化疫苗Ⅰ期临床反应及血清效果观察,免疫程序为0,1,2月,分原倍疫苗组和1∶2稀释组,各免15人,每针次免疫后连续观察3天,结果均无不良反应,仅在注射时稍有微胀痛感。二针次免疫后均能产生较高的免疫抗体:原倍疫苗免疫抗体滴度,ELISA1∶181(GET),PRNT中和抗体≥1∶10;1∶2稀释疫苗,ELISA1∶169(GMT),PRNT≥1∶10。三针次免疫后抗体滴度高于二针次;原倍疫苗,ELISA1∶478(GMT),PRNT1∶10～1∶20;稀释疫苗,ELISA1∶446(GMT),PRNT1∶10～1∶20,但原倍疫苗和稀释疫苗的抗体水平之间无显著性差异。半年后仍保持一定抗体水平。可采用二针次总量2ml免疫。

The phase Ⅰ Clinical trial of type Ⅱ Purified EHF Vaccine was approved by the rational contral authority in 1991. A lot (91001- 1 ) of type Ⅱ EHF vaccine was prepared with suckling mouse brain, using R22SM Strain ( type Ⅱ ) . It only cantains envelop glycoprotein G1, G2 and nucleocapsid protein N of EHF virus ( i. e. purified subunits vaccine of EHF virus ) . It was inactivated by 1:6000 β-propiolactone.The results on examination showed that no live virus was detected in vaccine after 3 Passages in Vero-E6 Cells; Antigen titers were 1:1024 by ELISA, 1 :512 by RPHA, 1 :64 by C. F. Neutralizing antibodies Produced in rabbite were ≥1 :20 by PRNT and Serum tilers were 1 :2048~4096 by ELISA to EHF Virus R22SM and LR1 strain after two injections with the vaccine, Befor inoeulation of human trial the said vaccine stored at 2-8 ℃ for 17 months. In order to study the immune response of type Ⅱ Purified vaccine, 30 Volunteers were divided in two group: group 1 were injected with undiluted vaccine and group 2 with diluted vaaccine. Fach of Volunteer of the two groups had been immunized intramuscularly ( 1ml ) tree time at an interval of 0 , 1,2 months, and observed 3 dogs continuously after each vaccination. According to the clinical trial and serologic data showed that none of all vaccinees developed fever or side offects or local and general reactions, After two injections ( 2 dose ) with type Ⅱ EHF vaccine, antibody titers were positive in all vaccinees of group 1 and 2 by ELISA, RPHI and PRNT. Seroconversion rate was 100%. Group 1 were ELISA 1 :181 (GMT), PRNT ≥1:10; Group 2 were ELISA 1 :16 9 ( GMT ) , PRNT≥1 = 10. After three injections ( 3 dores ) , immune antibody titers of vaccine was better than that of two inoculations. Group 1 were ELISA 1 :478(GMT),PRNT 1 :10~ 1 :20. Group 2 were ELISA 1 :446 ( GMT ) , PRNT 1 :10~1 :20. It following that there are no statistical difference between the vaccine in group 1and 2. both antibody titers remained at same level after half year of inoculation. These results indicated that the typo Ⅱ EHF purified vaccine appears to be safe and eff-ective for humans, and had highter immune activity, and conld be adopted two shot immunizations with a total of 2 ml. It can be used widely in urban and rural to proventive inoculation against EHF.