甲型肝炎减毒活疫苗(H_2株)的开发研究

1992年我国研究开发成功甲型肝炎 (甲肝 )减毒活疫苗 (H2 株 )。十几年中建立了普通狨猴动物模型 ;将细胞-病毒培养系统的生产工艺做了重大改进 ;对 1989～ 1997年生产的 16批疫苗做了现场人体观察 ,未见不良反应及血清丙氨酸氨基转移酶 (ALT)升高 ,接种后抗体阳转率为 81 8%～ 10 0 0 % ,几何平均滴度 (GMT)为 1∶2 1～ 1∶5 0。K7疫苗病毒为IB基因亚型 ,经体内外多次传代或从接种者排出的病毒做序列分析 ,其与K7株的同源性达99 3%～ 10 0 0 % ,显示减毒性质、遗传稳定性不变。易感者接种疫苗后粪便排毒率为 85 7%～ 90 3% ,接触者为6 3 6 %～ 71 9% ,说明活疫苗接种后有次传播能力 ,但毒株均显弱毒性质 ,无毒力返祖现象。结果表明 :H2 株甲肝减毒活疫苗的安全性、免疫原性良好 ,应该继续推广使用

Research and Development of Live Attenuated Hepatitis A Vaccine (H_2 Strain)

In 1992, the research and development of live attenuated hepatitis A vaccine (H2 strain) met with success in China. However, a great deal of studies related to the developmental research have been performed for more than 10 years. An animal model of hepatitis A virus(HAV) was established in common marmoset (Callithrix jacchus) which showed better sensitivity than rhesus monkey to HAV infection. The manufacturing technology, especially the cell-virus cultivation process has significantly been improved. Sixteen batches of vaccine produced in years of 1989-1997 have been taken for trial investigation. The responses of 2508 vaccinees inoculated with one dose of vaccine showed that neither side effects nor alanine aminotransferae (ALT) elevation was detected. The positive seroconversion rates was from 81.8% to 100% and the geometric mean titer(GMT) was between 2.1-5.0. The whole nucleotide sequence of vaccine virus (K 7) has been analyzed and the genome type of K 7 virus was classified into 1B subgenotype. Meanwhile, several nucleotide fragments were determined for the progeny viruses derived from K 7 virus by passing many times in cells or in marmosets as well as inoculating into human bodies. The homology rate between the progeny viruses and the parental K 7 virus was 99.3-100%, and the hereditary stability of the attenuated of live vaccine virus was revealed. The excreting rates of virus in feces of susceptible vaccinees and contacts were 85.7-90.3% and 63.6-71.9%, respectively. However, the shedding HAV strains showed attenuation with no phenomenon of virulence reversion when the virulence/attenuation level was examined in common marmoset. The live vaccine of H 2 strain has been demonstrated possessing the ability of secondary transmission but not inducing hepatitis A. In conclusion, the live attenuated hepatitis A vaccine (H 2 strain) has good safety and immunogenicity, and its application should continuously be expanded.