Induction of robust T cell response to RRV-LANA

诱导 T 细胞对 RRV-LANA 产生强烈反应

基本信息

批准号：
8774212
负责人：
SCOTT W WONG
金额：
$ 19.03万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-12-01 至 2015-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8774212
关键词：
Address Animal Model Animals Antigens B-Lymphocytes Biological Biopsy Blood Blood specimen Bronchoalveolar Lavage CD8B1 gene Control Groups Cytomegalovirus Cytomegalovirus Vaccines Development Disease Exhibits Genome HIV HIV-1 Health Herpesviridae Infections Human Human Herpesvirus 8 Hyperplasia Immune response Immunity Incidence Individual Infection Integration Host Factors Intravenous Kaposi Sarcoma Light Lung Lymphoproliferative Disorders Macaca mulatta Malignant Neoplasms Modeling Monitor Non-Hodgkin&apos s Lymphoma Organ Transplantation Outcome Pathogenesis Patients Peptides Population Property Rhadinovirus SIV Syndrome System T cell response T-Lymphocyte Techniques Testing Tissue Banks Tissue Sample Tissues Vaccinated Vaccination Vaccines Viral Load result Virus Virus Diseases acquired immunodeficiency cohort gamma-2 herpesvirus immunogenicity in vivo Model latency-associated nuclear antigen lymph nodes mutant nonhuman primate novel vaccines prevent response therapeutic vaccine vaccine evaluation vector

项目摘要

DESCRIPTION: Kaposi's sarcoma is the leading cancer observed in individuals with AIDS. In vivo models that can recapitulate most/all aspects of Kaposi's sarcoma-associated herpesvirus (KSHV) infection and disease are absolutely required to develop and test new vaccines to prevent the increase in KSHV infection and disease. Currently, the rhesus macaque (RM) model of KSHV-like disease fulfills most of these aspects, as animals experimentally infected with the simian immunodeficiency virus (SIV) and rhesus macaque rhadinovirus (RRV) develop B cell lymphoproliferative diseases (LPD) similar to AIDS patients co-infected with KSHV. Importantly, RM exhibit similar immunological responses to RRV infection, as humans infected with KSHV. Specifically, RM infected with RRV possess low CD4+ and CD8+ T cell responses to the virus, which could be one host factor that allows the virus to maintain a persistent infection. In this application, we intend to test the properties of the newly developed rhesus cytomegalovirus (RhCMV) vaccine vector system to stimulate a robust T cell response in RM that can recognize RRV latency-associated nuclear antigen (LANA). Once the immune responses to RRV LANA are characterized in vaccinated animals, the animals will be challenged with RRV and monitored for virus infection and persistence. The long-term objectives of this study aim to evaluate the ability of RhCMV vectors to induce a strong T cell response to RRV-LANA and whether this T cell immunity is capable of clearing RRV infection and persistence in a relevant model of KSHV infection. To address this, the following Specific Aims are proposed: Specific Aim 1: Immunogenicity of RhCMV US8-11-LANA in rhesus macaques. Specific Aim 2: Protection of RhCMV US8-11-LANA-vaccinated animals against challenge with wild type RRV.

描述：卡波西的肉瘤是在艾滋病患者中观察到的主要癌症。可以开发和测试新的疫苗以防止KSHV感染和疾病的增加，可以绝对需要概括Kaposi肉瘤相关疱疹病毒（KSHV）感染和疾病的大多数/所有方面的体内模型。目前，像KSHV样疾病的恒河猴模型（RM）模型达到了这些方面的大多数，因为通过实验感染了邻胺免疫缺陷病毒（SIV）和恒河猴猕猴rhadinovirus（RRV）B细胞淋巴细胞增强性疾病（LPD）类似于AIDS患者Co-kshv。重要的是，RM对RRV感染表现出类似的免疫反应，与受KSHV感染的人类相似。具体而言，感染RRV的RM具有低CD4+和CD8+ T细胞对病毒的反应，这可能是使病毒保持持续感染的宿主因子。在此应用中，我们打算测试新开发的颗粒状细胞瘤病毒（RHCMV）疫苗载体系统的性质，以刺激RM中可识别RRV潜伏期相关的核抗原（LANA）的RM中强大的T细胞反应。一旦对RRV LANA的免疫反应在疫苗接种的动物中被表征，将对动物进行RRV挑战并监测病毒感染和持久性。这项研究的长期目标旨在评估RHCMV载体诱导T细胞对RRV-LANA的强烈T细胞反应的能力，以及该T细胞免疫是否能够在KSHV感染的相关模型中清除RRV感染和持久性。为了解决这个问题，提出了以下特定目的：具体目标1：RHCMV US8-11-LANA在恒河猕猴中的免疫原性。具体目标2：保护RHCMV US8-11-LANA接种动物免受野生型RRV的挑战。