New Approaches to Passive and Active Immunoprophylaxis

被动和主动免疫预防的新方法

• 批准号: 6431698
• 负责人: Robert H. Purcell
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6431698
• 关键词: Baculoviridae; Callithricidae; Hepatovirus; Macaca mulatta; Pan; active immunization; attenuated microorganism; bone marrow; hepatitis A; hepatitis B; hepatitis B virus group; hepatitis C virus; hepatitis vaccine; hepatitis virus; immunomodulators; laboratory mouse; live vaccine; nonhuman therapy evaluation; oral administration; passive immunization; tissue /cell culture; vaccine development; vector vaccine; virus replication

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.

HVS与比利时里克森萨尔的SmithKline Beecham合作开发了几种候选的减毒活HAV疫苗。此外，HVS还开发了一种非常有前途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疫苗技术，其模型系统基于HVS具有丰富经验的B肝炎病毒（HBV）疫苗。我们目前正在测试免疫刺激剂（CpG）作为DNA疫苗和蛋白质疫苗佐剂的功效。 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）。DNA疫苗在小鼠和恒河猴中被证明具有高度免疫原性，在黑猩猩中具有中等免疫原性，但当黑猩猩受到活HCV的攻击时，它们并没有得到充分的保护。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中一直是重要的。然而，单克隆制剂可能更有效，针对特定的中和表位定制，并且效力高度一致。我们已经从黑猩猩的骨髓中制备了组合文库，这些黑猩猩已经被实验性地依次感染了五种人类肝炎病毒中的每一种。黑猩猩球蛋白几乎与人免疫球蛋白相同，使其成为免疫预防剂和免疫抑制剂的有吸引力的选择。