甲型肝炎灭活疫苗的研究

Studies and Preparation of an Inactivated Hepatitis A Virus Vaccine

目的研制甲肝灭活疫苗。方法甲型肝炎病毒TZ84株、吕8株接种人胚肺二倍体细胞2BS、KMB17株,经培养繁殖、收获、提纯、甲醛溶液灭活和氢氧化铝吸附制成灭活疫苗。结果纯化的甲肝病毒经HPLC、SDS-PAGE等方法检测表明具有良好的纯度。灭活工艺经验证盲传三代证明灭活可靠。甲肝灭活疫苗在豚鼠、小白鼠、ICR小鼠、恒河猴和普通狨猴上具有良好的安全性和免疫原性;经539例临床研究表明,该疫苗儿童组和成人组副反应均轻微,全程免疫后接种者100％抗体阳转,儿童组0,6月注射500u全程免疫后抗体水平达4535mIU/ml,成人组注射500u 0,6月全程免疫后抗体水平为1657mIU/ml,均可获得较长期的保护效果;该疫苗2～8℃保存21个月、37℃保存32天,质量稳定。结论甲肝灭活疫苗安全、有效、稳定。

Objective To develop an inactivated hepatitis A virus (HAV) vaccine. Methods HAV strain TZ84 and Liu8, adapted to propagate in human diploid cells (strain 2BS and KMB17) which are acceptable for human vaccine manufacture, was highly purified, inactivated with formalin, absorbed to aluminium hydroxide, and detected for capacity to elicit antibody to HAV in both animals and human beings. Result Analysis by electron microscope, HPLC, SDS- poly-acrylamide gels indicated a high degree of purity of the purified HAV preparation. Evidence for successful inactivation of the purified HAV preparation by 1:4000 formalin was obtained in cell culture inoculated with three lots formalin - inactivated HAV. The vaccines were safe and high in Cuinea pigs, mice and marmosets, and induced protection against challenge in marmosets. The vaccines were safe and well tolerated in the clinical trial of 539 volunteers, and were high immunogenicity as all subjects had observed seroconversion after the full the vaccination course. Children and adults administered 500u in 0, 6 month achieved and - HAV antibody geometric mean titre (GMT) value of 4535 mIU/ml and 1657 mIU/ml respectively. The results showed effective against HAV infection. The vaccines stored at 2～ 8℃ for 21 months and 37℃ for 32days were also stable. Conclusion The inactivated HAV vaccines are safe, immmunologic and stable.