Peetermans J
SmithKline Beecham Biologicals, Rixensart, Belgium.
Vaccine. 1992;10 Suppl 1:S99-101. doi: 10.1016/0264-410x(92)90557-z.
The isolation and adaptation of hepatitis A virus to cell culture opened the way to the development of vaccines. Based on experience with inactivated poliovaccines, a similar approach was chosen for the development of an inactivated hepatitis A vaccine. Strain HM175, adapted to MRC-5 human diploid cells, was used as the virus strain. Vaccine production starts with growth and multiplication of the seed virus in MRC-5 cells. The harvests are clarified, purified and concentrated. Inactivation by formaldehyde is carried out on a pool of purified harvests. Close control of all process parameters results in consistent production of completely inactivated and highly immunogenic vaccine lots. Quality control testing is based on the general requirements for biologicals of WHO and National Control Authorities. Tests have been developed and validated to show the purity of the cell substrate used for each production cycle, the quality of the virus harvest, the adequacy of the purification and inactivation processes, and the conformity to stringent specifications for purity, safety and potency of the final bulk vaccine filled in final containers. The vaccine is characterized by adequate identity tests, by its reaction with polyclonal and monoclonal antibodies, by its immunogenicity in laboratory animals and by the detailed study of the immune response in primates and human volunteers. The final result of the development of adequate production and testing methods, confirmed by extensive characterization studies, is the availability of a consistent, safe and potent hepatitis A vaccine.
甲型肝炎病毒的细胞培养分离与适应性培养为疫苗的研发开辟了道路。基于灭活脊髓灰质炎疫苗的经验，在甲型肝炎灭活疫苗的研发中采用了类似的方法。适应MRC - 5人二倍体细胞的HM175株被用作病毒株。疫苗生产始于种子病毒在MRC - 5细胞中的生长和繁殖。收获物经过澄清、纯化和浓缩。对纯化收获物的混合液进行甲醛灭活。对所有工艺参数进行严格控制，确保始终如一地生产出完全灭活且免疫原性高的疫苗批次。质量控制检测基于世界卫生组织和国家监管当局对生物制品的一般要求。已开发并验证了相关检测方法，以证明每个生产周期所用细胞基质的纯度、病毒收获物的质量、纯化和灭活工艺的充分性，以及最终灌装在最终容器中的半成品疫苗在纯度、安全性和效力方面符合严格的规格要求。该疫苗通过充分的鉴别试验、与多克隆和单克隆抗体的反应、在实验动物中的免疫原性以及对灵长类动物和人类志愿者免疫反应的详细研究来表征。通过广泛的特性研究证实，适当的生产和检测方法研发的最终成果是获得了一种始终如一、安全且有效的甲型肝炎疫苗。
