Induction of robust T cell response to RRV-LANA

描述：卡波西肉瘤是艾滋病患者中观察到的主要癌症。绝对需要能够概括卡波西肉瘤相关疱疹病毒（KSHV）感染和疾病的大多数/所有方面的体内模型来开发和测试新疫苗，以防止KSHV感染和疾病的增加。目前，KSHV样疾病的恒河猴（RM）模型实现了这些方面中的大部分，因为实验性感染猿猴免疫缺陷病毒（SIV）和恒河猴鼻状病毒（RRV）的动物发展出与共感染KSHV的AIDS患者相似的B细胞淋巴增生性疾病（LPD）。重要的是，RM对RRV感染表现出与感染KSHV的人相似的免疫应答。具体而言，感染RRV的RM对病毒具有低的CD 4+和CD 8 + T细胞应答，这可能是允许病毒维持持续感染的一个宿主因素。在本申请中，我们打算测试新开发的恒河猴巨细胞病毒（RhCMV）疫苗载体系统的特性，以刺激RM中可识别RRV潜伏相关核抗原（拉娜）的强大T细胞应答。一旦在接种动物中表征了对RRV拉娜的免疫应答，将用RRV攻毒动物并监测病毒感染和持续性。本研究的长期目标旨在评价RhCMV载体诱导对RRV-LANA的强烈T细胞应答的能力，以及这种T细胞免疫是否能够清除RRV感染并在KSHV感染的相关模型中持续存在。为了解决这一问题，提出了以下特定目的：特定目的1：RhCMV US 8 -11-拉娜在恒河猴中的免疫原性。具体目的2：保护RhCMV US 8 -11-LANA疫苗接种的动物免受野生型RRV的攻击。

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.