A THERAPEUTIC VACCINE FOR EBV-ASSOCIATED MALIGNANCIES

一种治疗 EB 病毒相关恶性肿瘤的疫苗

• 批准号: 8358021
• 负责人: Frederick C. Wang
• 金额: $ 6.84万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8358021
• 关键词: AIDS-Related Lymphoma; Adenovirus Vector; Animal Model; EBV-associated malignancy; Epstein-Barr Virus Infections; Funding; Goals; Grant; Human; Human Herpesvirus 4; Immune; Immune response; Lymphocryptovirus; Lymphomagenesis; Macaca mulatta; Malignant Neoplasms; National Center for Research Resources; New England; Pan Genus; Primates; Principal Investigator; Proteins; Research; Research Infrastructure; Resources; Serotyping; Simplexvirus; Source; Testing; United States National Institutes of Health; Vaccines; Viral; Viral Proteins; arm; base; cost; immunogenicity; novel therapeutics; therapeutic vaccine; tumor; vector vaccine

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The goal of the application is to develop a novel therapeutic vaccine to Epstein-Barr virus (EBV) and its associated malignancies. EBV infection is responsible for the majority of AIDS-associated lymphomas. We propose to target the viral-encoded protein, EBNA1, which is the only viral protein consistently expressed in all EBV-associated malignancies. The vaccine will incorporate the fusion of the HSV gD protein to EBNA1 to overcome a negative regulatory arm of the adaptive immune response that has been implicated in tumor-associated immune escape. The vaccine vector will be derived from the E1-deleted adenoviral vectors based on the chimpanzee-serotype 68 (AdC68) to eliminate background immunogenicity to more common human serotypes. The vaccine will be tested in rhesus macaques, using the rhesus lymphocryptovirus (rhLCV) as the most appropriate animal model for EBV lymphomagenesis.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 该申请的目标是开发一种针对EB病毒（EBV）及其相关恶性肿瘤的新型治疗性疫苗。EB病毒感染是大多数艾滋病相关淋巴瘤的原因。我们建议靶向病毒编码的蛋白EBNA 1，这是唯一一种在所有EBV相关恶性肿瘤中一致表达的病毒蛋白。该疫苗将整合HSV gD蛋白与EBNA 1的融合，以克服与肿瘤相关的免疫逃逸有关的适应性免疫应答的负调节臂。疫苗载体将源自基于黑猩猩血清型68（AdC 68）的E1缺失腺病毒载体，以消除对更常见人类血清型的背景免疫原性。将在恒河猴中检测疫苗，使用恒河猴淋巴隐病毒（rhLCV）作为EBV淋巴瘤发生的最合适动物模型。