Core 3: Non-human Primate Core

摘要-核心3 目前的SARS-CoV-2大流行是过去两年中由betaCoV引起的第三次重大病原性爆发 几十年用于2b组和2c组β CoV的泛β冠状病毒（panbetaCoV）疫苗的开发是 这是P01的主要优先事项。此外，该P01将评价甲病毒复制子、修饰的mRNA-脂质 纳米颗粒和蛋白质纳米颗粒作为泛β CoV疫苗平台。非人灵长类动物（NHP），如 由于食蟹猴或恒河猴已被NHP Core 3团队证明是SARS的优秀模型， CoV-2感染。NHP是疫苗设计和测试的重要组成部分， 生理和免疫学上与人类相似。NHP Core 3将支持P01， 遵循具体目标：目标1。泛β-CoV中和抗体疫苗的保护力试验 使用食蟹猴或恒河猴作为动物模型。来源于以下的向下选择的B细胞疫苗 项目1、2、3或4将在NHP模型中进行测试。我们假设猕猴会成为 蝙蝠或穿山甲冠状病毒的收购，因为他们是人类原型组2b冠状病毒（SARS-CoV-1和2）， 2C组人类病毒MERS目标2.检测基于T细胞的泛β CoV疫苗的保护能力 使用食蟹猴或恒河猴作为动物模型。CD 8 T细胞应答已被证明是一种免疫应答。 恒河猴SARS-CoV-2免疫保护相关成分。这里的假设是 靶向T细胞的疫苗可以与B细胞疫苗协同作用，以提高保护作用， 抗体滴度。将在NHP模型中测试来自项目4的向下选择的T细胞疫苗，其中T细胞 将通过逐步基于表位的方法，使用包括基于IFN-γ的 ELISpot、基于多参数流式细胞术的测定和10 X基因组学转录组分析。目标3. 通过panbetaCoV疫苗监测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学和增强的BAL细胞因子和肺CoV PFU。因此，在本发明中， NHP Core 3将是P01的组成部分，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.