Human gamma herpes virus DNA vaccines

人类伽马疱疹病毒 DNA 疫苗

• 批准号: 6383178
• 负责人: Dirk P Dittmer
• 金额: $ 25.61万
• 依托单位: OKLAHOMA MEDICAL RESEARCH FOUNDATION
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-30 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6383178
• 关键词: Callithricidae; Epstein Barr virus; Gammaherpesvirinae; Herpesviridae disease; Herpesviridae vaccine; Macaca mulatta; active immunization; human herpesvirus 8; laboratory mouse; vaccine development; vector vaccine

Human gamma herpesviruses include Epstein-Barr virus (EBV or HHV- 4) and Kaposi's Sarcoma herpesvirus (KSHV or HHV-8). Both are oncogenic and have a chronic latent phase of infection, which leaves humans hosts infected for life. We hope to adapt the current knowledge of these viruses to develop DNA vaccines. Our purpose is to facilitate the elimination or relative suppression of Kaposi's sarcoma (especially in AIDS patients), as caused by KSHV, and of the latent EBV infection found in normals or expressed in some lymphomas, Hodgkin's disease, nasopharyngeal carcinomas, post-transplant lymphoproliferative disease, and infectious mononucleosis. These are over 150 gene products from which to select the targets for a DNA vaccine, as measured by the number of open reading frames in EBV and KSHV. We plan to begin this project (Specific Aim 1) by constructing DNA vaccines directed against four viral gene products, the TSAs ("tumor specific antigens"): LANA (latency associated nuclear antigen) and v-cyclin form KSHV and LMP-1 ((latent membrane protein) and LMP-2A from EBV. The immunogenicity and optimal vaccination strategy will be evaluated and developed in Balb/c mice (Specific Aim 2), where suppression of the transformed phenotype is expected using appropriately engineered vectors with, the 10(3) cell line. (Additional modifications may be needed for LMP-2A, which is the only one of the four TSAs not known to be oncogenic.) Finally, in preparation for future human studies we will test the DNA vaccines in non-human primates (Specific Aim 3). The suppression of EBV-induced lymphomas by the DNA vaccines will be assessed in Cotton top tamarins. Similarly, the acceleration of KSHV elimination will be assessed in DNA vaccine immunized Rhesus macaques. This experience and the immunologic evaluations performed will hopefully be preparatory for a successful trial of one or more of these gamma herpes virus vaccines in man.

人γ疱疹病毒包括爱泼斯坦 - 巴尔病毒（EBV或HHV-4）和卡波西的肉瘤疱疹病毒（KSHV或HHV-8）。两者都是致癌的，并且具有慢性潜在感染期，这使人类寄托着感染生命。我们希望适应这些病毒的当前知识，以开发DNA疫苗。我们的目的是促进KAPOSI肉瘤（尤其是在艾滋病患者中）的消除或相对抑制，这是由KSHV引起的，以及在某些淋巴瘤，霍奇金氏病，鼻咽癌癌，转移后淋巴细胞症状的淋巴细胞症，转移性淋巴细胞症和虚拟症中，霍奇金氏病，霍奇金氏病，霍奇金氏病，霍奇金氏病，hodgkin疾病，和infositious monoyuctious monoyuctious monononic sonononuctious，是在某些淋巴瘤中表达的潜在EBV感染。这些超过150种基因产物可以从中选择DNA疫苗的靶标，如EBV和KSHV中的开放式阅读帧数所测量。我们计划通过构建针对四种病毒基因产物的DNA疫苗（特定目的1）开始该项目（“肿瘤特异性抗原”）：LANA（与潜伏期相关的核抗原）和V-Cyclin形成KSHV和LMP-1（（潜在的膜蛋白）和LMP-2A的特定于免疫性和最佳效果。目的2），使用适当的工程矢量抑制10（3）个细胞系（LMP-2A可能需要其他修改）。 DNA疫苗将在棉花顶部的tamarins中进行评估。