Innate Immune Responses and Vaccines Against Tumor-Associated Herpesviruses

先天免疫反应和针对肿瘤相关疱疹病毒的疫苗

基本信息

批准号：
8659738
负责人：
REN SUN
金额：
$ 173.24万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-19 至 2019-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8659738
关键词：
Acute Address Africa Area Benign Budgets Case Study Cells Child Complement Critiques Data Defense Mechanisms Developing Countries Development Disease Evolution Foundations Functional RNA Future Goals Hepatitis B Virus Herpesviridae Herpesviridae Infections Host Defense Mechanism Human Human Herpesvirus 4 Human Herpesvirus 8 Human Papillomavirus Immune Immune response Incidence Infection Infection prevention Institution Interferons Kaposi Sarcoma Knowledge Leadership Life Lymphocyte Malignant Neoplasms Maps Medical MicroRNAs Modeling Molecular Mus Natural Immunity Principal Investigator Proteins Rana Recommendation Reporting Research Personnel Resources Role Satellite Viruses Services The Sun Translational Research Vaccine Adjuvant Vaccine Design Vaccines Vertebrates Viral Virus War Work defense response design gammaherpesvirus human subject protection in vivo infection related cancer latent infection member novel novel vaccines pathogen prevent programs response tumor vaccine candidate vaccine development virology

项目摘要

DESCRIPTION (provided by applicant): Through co-evolution with hosts, herpesviruses have acquired strategies to exploit their hosts, allowing their own life-long persistence while intermittently being secreted and transmitted to naive hosts. By evading host defense mechanisms, herpesviruses can persist in hosts and cause various diseases. Members of the gamma-herpesvirus subfamily (Epsetin-Barr virus, Kaposi's sarcoma-associated herpesviruses and gamma herpesvirus-68) are distinct in their ability to establish latent infections in lymphocytes and cause benign or malignant tumors in infected hosts. It remains elusive how gamma-herpesviruses evade host innate immunity during their acute and persistent infections. Understanding the mechanisms of viral evasion mechanism is essential for developing approaches to prevent or control the virus associated cancers. Innate immunity is not only the first line of defense against pathogens, but is also critical for stimulating adaptive immune responses. The objective is to understand the mechanisms by which cells mount innate defense responses and tumor-associated-herpesviruses thwart components of the defense mechanisms, to establish a foundation for rational design of vaccine candidates that can elicit effective immune responses and reduce associated cancer incidence. There are four projects: 1) Interactions of gamma-herpesviruses with NLRs (Cart Ware); 2) Regulators of innate immune responses to gamma-herpesvirus infection (Sumit Chanda); 3) Role of microRNAs in regulating host interactions (Tariq Rana); 4) Restoring immune responses to gamma-herpesviruses (Ren Sun); coordinated by an Administrative Core (Ren Sun) and facilitated by a Virology Technical Service Core (Ting-Ting Wu). A team of investigators with diverse and complementing expertise has been working together and obtained critical preliminary data as the foundation for the Program. The understanding of the molecular and cellular mechanisms underlying the interactions between virus-host innate defenses will be utilized to develop a new vaccine strategy. This translational research program will provide critical information for vaccine development to prevent cancers associated with gamma-herpesviruses.

描述（由申请人提供）：通过与宿主的共同发展，疱疹病毒已经获得了利用宿主的策略，允许他们自己的终身持久性，同时间断地分泌并传播给天真的寄主。通过逃避宿主防御机制，疱疹病毒可以持续存在于宿主并引起各种疾病。伽马病毒亚科（Epsetin-Barr病毒，Kaposi与肉瘤相关的疱疹病毒和伽马疱疹病毒-68）的成员在淋巴细胞中建立潜在感染并引起受感染宿主的良性或恶性肿瘤。伽马病毒在急性和持续感染期间逃避了先天免疫，这仍然是难以捉摸的。了解逃避病毒机制的机制对于开发预防或控制病毒相关癌症的方法至关重要。先天免疫不仅是针对病原体的第一道防线，而且对于刺激适应性免疫反应至关重要。目的是了解细胞安装先天防御反应的机制和与肿瘤相关的疱疹病毒阻止防御机制的组成部分，以建立候选疫苗的合理设计基础，这些疫苗可以引起有效的免疫反应并减少相关癌症的发生率。有四个项目：1）γ-HERPESVIRUS与NLR的相互作用（CART WARE）； 2）对伽马病毒感染的先天免疫反应调节因子（Sumit Chanda）； 3）microRNA在调节寄主相互作用（Tariq Rana）中的作用； 4）恢复对γ-疱疹病毒（Ren Sun）的免疫反应；由行政核心（Ren Sun）协调，并由病毒学技术服务核心（Ting-ting Wu）促进。具有多样化和补充专业知识的调查员团队一直在合作，并获得了关键的初步数据，作为该计划的基础。将利用对病毒宿主先天防御之间相互作用的分子和细胞机制的理解来制定一种新的疫苗策略。该转化研究计划将为疫苗开发提供关键信息，以防止与γ-疱疹病毒相关的癌症。