Core-- Animal Models

动物模型核心，将在SARS冠状病毒疫苗中起到三个主要目的 发展计划。1)核心将开发用于评估野生型SARS-CoV诱导的免疫反应的标准化分析和试剂，以及项目1-4和核心C中开发的携带活的减毒、灭活和复制子载体的SARS-CoV候选疫苗小组。2)核心将评估在该计划项目中开发的重组突变体SARS-CoV在最近发展的小鼠模型中对体内复制的影响，以及在SARS-CoV诱导的疾病的雪貂模型中的体内复制和致病机制。这些研究将对SARS-CoV呼吸道感染中特定病毒基因在发病机制中的作用提供重要的见解。还预计在这一核心范围内的研究 将鉴定减毒SARS-CoV突变体，其在雪貂中的安全性特征将使它们成为很好的减毒活疫苗候选者。3)CORE将对在雪貂模型中被证明是安全的SARS-CoV减毒活疫苗以及灭活疫苗和复制子交付的疫苗进行面对面的比较。这些研究将对每种疫苗在小鼠和雪貂模型中安全地诱导SARS-CoV特异性免疫反应和保护其免受SARS-CoV攻击的能力进行深入和逐步的评估。这个核心的最终目标，以及整个计划项目，都是为了开发 候选人接种的减毒活疫苗、灭活疫苗或载体疫苗将安全有效地预防SARS-CoV感染。在小鼠和雪貂模型中安全地诱导对SARS冠状病毒攻击的保护性免疫的疫苗，将被认为是在非人类灵长类动物中进行额外安全性和有效性测试的良好候选者。具体目标： 目的1.免疫应答检测方法的建立和优化目的2.评价重组SARS-CoV在小动物模型中的复制和疾病表型。目的3.评价减毒活疫苗、灭活疫苗、VLP疫苗和重组载体疫苗诱导保护性免疫应答的效果。

The Animal Models Core, will serve three major purposes within the SARS Coronavirus Vaccine Development Program. 1) The core will develop standardized assays and reagents for evaluating the immune responses induced by wild-type SARS-CoV, as well as the panel of live attenuated, inactivated, and replicon vector delivered SARS-CoV vaccine candidates developed in projects 1-4 and Core C. 2) The core will evaluate the recombinant mutant SARS-CoV developed in this program project for effects on in vivo replication in a recently developed mouse model, and in vivo replication and pathogenesis in a ferret model of SARS-CoV-induced disease. These studies will provide important insights in to the role of specific viral genes in the pathogenesis of SARS-CoV respiratory infection. It is also expected that studies within this core will identify attenuated SARS-CoV mutants that whose safety profiles in the ferret will make them good candidates as live attenuated vaccines. 3) The core will perform a head to head comparison of live attenuated SARS-CoV vaccines that prove safe in the ferret model, as well as inactivated and replicon delivered vaccines. These studies will involve an in depth and stepwise assessment of each vaccine's ability to safely induce SARS-CoV specific immune responses and to protect from SARS-CoV challenge in the mouse and ferret models. The ultimate goal of this core, as well as the program project as a whole, is to develop candidate live attenuated, inactivated, or vector delivered vaccines that will safely and effectively protect against SARS-CoV infection. Vaccines that safely induce protective immunity against SARS-CoV challenge in the mouse and ferret models, will be considered to be good candidates for additional safety and efficacy testing in non-human primates. Specific Aims: Aim 1. Immune response assay development and optimization Aim 2. Evaluation of recombinant SARS-CoV for replication and disease phenotypes in small animal models. Aim 3. Evaluation of live attenuated, inactivated, VLP, and recombinant vector-based SARS-CoV vaccines for induction of protective immune responses.