New Approaches to Passive and Active Immunoprophylaxis

HVS与比利时Rixensart的SmithKline Beecham公司合作开发了几种候选HAV减毒活疫苗。此外，HVS还开发了一种重组戊型肝炎候选疫苗，该疫苗非常有希望，目前正在临床试验中。HVS正在研究以乙型肝炎病毒（HBV）疫苗为基础的模型系统的DNA疫苗技术，HVS在乙肝疫苗方面有丰富的经验。我们目前正在测试一种免疫刺激剂（CpG）作为DNA疫苗和蛋白质疫苗的佐剂的功效。此外，正在探索DNA疫苗用于控制丙型肝炎病毒（HCV）的效用。这些研究扩展到非人类灵长类动物（恒河猴和黑猩猩）。一种DNA疫苗被证明在小鼠和恒河猴中具有高度免疫原性，在黑猩猩中具有中等免疫原性，但是当黑猩猩受到活的HCV攻击时，它们并没有得到完全的保护。被动免疫预防也是一项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中很重要。然而，单克隆制剂可能更有效，针对特定的中和表位进行定制，并且效力高度一致。我们从黑猩猩的骨髓中准备了组合文库，这些黑猩猩在实验中按顺序感染了五种人类肝炎病毒中的每一种。黑猩猩的免疫球蛋白与人类的免疫球蛋白几乎相同，这使它们成为免疫预防和免疫治疗药物的有吸引力的选择。

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.