D'Hondt E
SmithKline Beecham Biologicals, Rixensart, Belgium.
Vaccine. 1992;10 Suppl 1:S48-52. doi: 10.1016/0264-410x(92)90542-r.
More than a decade ago, successful replication of hepatitis A virus (HAV) in cell culture opened the way to the development of live attenuated and inactivated vaccine candidates. Serial passages of HAV in cell culture led to attenuation as demonstrated by experiments in non-human primates. Several live vaccine candidates obtained through serial passages have been evaluated in volunteers. Significant improvements in the yield of viral antigen from infected cell cultures stimulated the development of killed vaccine candidates. These formalin-inactivated vaccines contain the viral capsid antigens assembled into viral particles. The immunogenic potential of the vaccine candidates depends strongly on the preservation of the configuration of the capsid proteins. Synthetic peptides covering immunogenic sequences of VP1 as well as soluble capsid proteins expressed as fusion proteins in Escherichia coli were therefore only weakly immunogenic when injected at high concentrations in rabbits. On the other hand, tamarin monkeys immunized with a live recombinant vaccinia expressing P1 were protected against virulent challenge. There are, however, considerable drawbacks related to the use of live vaccinia as a carrier virus. Chimeric polio-HAV VP1 viruses have been constructed. These hybrid viruses were not able to induce an immune response, probably because of configurational constraints of poliovirus on the inserted HAV epitopes. More recently, encouraging data on empty virus particles expressed in baculovirus and vaccinia virus systems have been reported.
十多年前，甲型肝炎病毒（HAV）在细胞培养中的成功复制为减毒活疫苗和灭活疫苗候选物的开发开辟了道路。HAV在细胞培养中的连续传代导致其减毒，这在非人类灵长类动物实验中得到了证明。通过连续传代获得的几种活疫苗候选物已在志愿者中进行了评估。感染细胞培养物中病毒抗原产量的显著提高刺激了灭活疫苗候选物的开发。这些福尔马林灭活疫苗含有组装成病毒颗粒的病毒衣壳抗原。疫苗候选物的免疫原性潜力在很大程度上取决于衣壳蛋白构型的保留。因此，覆盖VP1免疫原性序列的合成肽以及在大肠杆菌中作为融合蛋白表达的可溶性衣壳蛋白，在以高浓度注射到兔子体内时，免疫原性很弱。另一方面，用表达P1的重组痘苗病毒活疫苗免疫的绢毛猴对强毒攻击具有抵抗力。然而，使用活痘苗作为载体病毒存在相当多的缺点。已经构建了嵌合脊髓灰质炎-HAV VP1病毒。这些杂种病毒无法诱导免疫反应，可能是由于脊髓灰质炎病毒对插入的HAV表位的构型限制。最近，有报道称在杆状病毒和痘苗病毒系统中表达的空病毒颗粒有令人鼓舞的数据。
