Core 3: Non-human Primate Core

摘要-核心3 目前的SARS-CoV-2大流行是过去两年由BetaCov引起的第三次重大致病疫情 几十年。针对2b组和2c组B组冠状病毒的潘贝塔冠状病毒疫苗的研制 这是P01的一大重点。此外，P01还将评估甲型病毒复制子、修饰的信使核糖核酸脂 纳米粒子和蛋白质纳米粒子作为泛美冠状病毒疫苗平台。非人灵长类(NHP) 由于NHP Core 3团队已经证明食蟹猴或恒河猴是SARS的优秀模型- 获取CoV-2。NHP是疫苗设计和测试的重要组成部分，因为它们具有解剖学上的， 在生理和免疫学上与人类相似。NHP Core 3将通过实现以下目标支持P01 具体目标如下：目的1.检测潘贝塔柯萨奇病毒中和抗体疫苗的保护能力 以食蟹猴或恒河猴为动物模型。被下调选择的B细胞疫苗源自 项目1、2、3或4将在NHP模型中进行测试。我们假设猕猴将成为优秀的模特儿 蝙蝠或穿山甲冠状病毒的获得率与人类2b组原型冠状病毒(SARS-CoV-1和2)的获得率相同 2c组人类病毒，MERS。目的2.检测潘贝塔冠状病毒T细胞疫苗的保护能力 以食蟹猴或恒河猴为动物模型。CD8 T细胞反应已被证明是一种 恒河猴抗SARS-CoV-2的免疫相关成分。这里的假设是 以T细胞为靶标的疫苗可以与B细胞疫苗协同作用，以低中和作用改善保护 抗体效价。从项目4中提取的下调选择的T细胞疫苗将在NHP模型中进行测试，其中T细胞 反应将通过逐步的基于表位的方法进行评估，方法包括基于干扰素-γ的分析 ELISPOT、基于多参数流式细胞术的分析和10倍基因组转录组分析。目标3. 监测潘贝塔冠状病毒疫苗在猕猴中的疫苗相关疾病增强(VAED)。 我们将监测接种疫苗的猕猴的肺部病理，并增强BAL细胞因子和肺冠状病毒PFU。因此， NHP Core 3将是P01的一个组成部分，也是P01成功的关键。

Abstract - Core 3 The current SARS-CoV-2 pandemic is the third major pathogenic outbreak caused by a betaCoV in the last two decades. Development of panbetacoronavirus (panbetaCoV) vaccines for group 2b and group 2c beta CoVs is a major priority of this P01. In addition, this P01 will evaluate alphavirus replicons, modified mRNA-lipid nanoparticles and protein nanoparticles as panbetaCoV vaccine platforms. Nonhuman primates (NHPs) such as cynomolgus or rhesus macaques have been shown by the NHP Core 3 team to be excellent models of SARS- CoV-2 acquisition. NHPs are important components of vaccine design and testing as they have anatomical, physiological and immunological similarities to humans. The NHP Core 3 will support the P01 by achieving the following Specific Aims: Aim 1. Test the protectivecapacityof panbetaCoVneutralizing antibodyvaccines using cynomolgus or rhesus monkeys as animal models. Down-selected B cell vaccines derived from Projects 1, 2, 3 or 4 will be tested in NHP models. We hypothesize that macaques will be as excellent models of bat or pangolin CoV acquisition as they are for human prototype group 2b CoVs (SARS-CoV-1 and 2) and group 2c human virus, MERS. Aim 2. Test the protective capacity of panbetaCoV T cell basedvaccines using cynomolgus or rhesus monkeys as animal models. CD8 T cell responses have been shown to be a component of immune correlates of protection from SARS-CoV-2 in rhesus macaques. The hypothesis here is that a T cell-targeted vaccine can synergize with B cell vaccines to improve protection with low neutralizing antibody titers. Down-selected T cell vaccines derived from Project 4 will be tested in NHP models, whereT cell responses will be assessed through a step-wise epitope-based approach using assays including IFN-γ-based ELISpot, multi-parameter flow cytometry-based assays, and 10X genomics transcriptome analysis. Aim 3. Monitor Vaccine Associated Enhancement of Disease (VAED) in macaques by panbetaCoV vaccines. We will monitor vaccinated macaques for lung pathology and enhancedBAL cytokines and lung CoV PFU. Thus, NHP Core 3 will be an integral component of this P01 and key to P01 success.