New Approaches to Passive and Active Immunoprophylaxis

HVS与比利时Rixensart的SmithKline Beecham合作开发了几种候选甲型肝炎减毒活疫苗。此外，人类免疫研究所还开发了一种前景看好的候选重组戊型肝炎疫苗，目前正在进行临床试验。HVS正在研究DNA疫苗的技术，并建立了一个基于乙肝疫苗的模型系统，HVS在乙肝疫苗方面已经有了丰富的经验。我们目前正在测试一种免疫刺激剂(CpG)作为DNA疫苗和蛋白质疫苗佐剂的有效性。此外，正在探索DNA疫苗用于控制丙型肝炎病毒(丙型肝炎病毒)的用途。这些研究扩展到非人类灵长类动物(恒河猴和黑猩猩)。事实证明，DNA疫苗在小鼠和恒河猴身上具有高度的免疫原性，在黑猩猩身上具有中等的免疫原性，但当黑猩猩受到活病毒的攻击时，它们并没有得到完全的保护。被动免疫预防也是一种重要的公共卫生工具。例如，正常的免疫球蛋白在预防甲型肝炎方面一直很重要。然而，单抗制剂可能更有效，为特定的中和表位量身定做，效力高度一致。我们从实验中先后感染了五种人类肝炎病毒的黑猩猩的骨髓中制备了组合文库。黑猩猩的球蛋白与人类的免疫球蛋白几乎完全相同，这使它们成为免疫预防和免疫治疗药物的诱人选择。

The HVS in collaboration with SmithKline Beecham, Rixensart, Belgium, has developed several candidate live attenuated HAV vaccines. In addition, the HVS has developed a candidate recombinant hepatitis E vaccine that is highly promising and that is currently in clinical trials. The HVS is studying the technology of DNA vaccines with a model system based upon hepatitis B virus (HBV) vaccine, a vaccine with which the HVS has had extensive experience. We are currently testing the efficacy of an immunostimulant (CpG) as an adjuvant for DNA vaccines, as well as for protein vaccines. In addition, the utility of DNA vaccines for the control of hepatitis C virus (HCV) is being explored. These studies were extended to non-human primates (rhesus monkeys and chimpanzees). A DNA vaccine proved to be highly immunogenic in mice and rhesus monkeys and moderately immunogenic in chimpanzees, but the chimpanzees were not fully protected when they were challenged with live HCV.Passive immunoprophylaxis has also been an important public health tool. For example, normal immunoglobulin has been important in the prevention of hepatitis A. However, monoclonal preparations could be more potent, tailored to specific neutralization epitopes and highly consistent in potency. We have prepared combinatorial libraries from the bone marrow of chimpanzees that had been experimentally infected in sequence with each of the five human hepatitis viruses. Chimpanzee globulins are virtually identical to human immunoglobulins, making them attractive choices for immunoprophylactic and immunotherapeutic agents.