Non Human Primate Core and the S. dysenteriae Vaccine Development Study - MARGE

优化利用非人类灵长类动物进行生物防御研究需要一种设施，使动物 在适当的生物容器中，研究人员在所需的方法学方面经验丰富 传染病研究和疫苗开发，以及开发必要的试剂 进行最先进的免疫学研究。这些责任的广度和程度是 最好是由一家以上机构组成的财团来满足。为此，灵长类动物设施在 匹兹堡大学和马里兰大学正在分享这些努力。具体地说，我们将 为非人类灵长类动物提供最先进的BSL3设施。我们还将提供我们广泛的 非人灵长类动物在发病机制研究和疫苗开发中的应用经验 艾滋病、结核病和其他感染性病原体，用于与A/B类药物的类似研究。此外， 我们将为食蟹猴的免疫功能分析提供必要的试剂 物种。食蟹猴为感染A/B类病原体提供了理想的模型，因为它们 都是容易感染这些病原体的，而且很容易获得。然而，一些试剂 缺乏评估该物种免疫反应所需的信息。我们建议解决这些问题 限制如下：1.食蟹猴的MHC I类基因座将是遗传的 特征，以及在已确定的种群中发现的最常见的基因座。多肽结合基序特异性 对于A类试剂，将进一步确定用作T细胞分析的试剂，以更好地定义和 量化免疫反应的特异性，并追踪粘膜组织的效应者群体。这些 研究将通过与匹兹堡大学的科学家和 爱普生公司是这项研究的先驱，致力于恒河猴的研究。2.细胞因子/趋化因子微阵列 将开发食蟹猴的特效药，以评估致病机制并进行分析 对疫苗的免疫反应。3.志贺菌粘膜免疫灵长类动物模型的建立 挑战赛将在马里兰大学开发，并被描述为上述活动的一部分 协作。总之，这些努力将提供一个理想的环境，用于开发和测试 本申请中提出的方法。

Optimal utilization of nonhuman primates for biodefense research requires a facility whereby animals are housed in appropriate biocontainment, research personnel experienced in the methodologies required for infectious disease research and vaccine development, and development of the necessary reagents to perform state-of-the-art immunological research. The breadth and magnitude of these responsibilities are best met by a consortium of more than one institution. Toward this end, the primate facilities at the University of Pittsburgh and the University of Maryland are sharing in these efforts. Specifically, we shall provide state-of-the-art BSL3 facilities for nonhuman primates. We shall also make available our extensive experience in the utilization of nonhuman primates for pathogenesis research and vaccine development for AIDS, tuberculosis, and other infectious agents for use in similar studies with category A/B agents. Further, we will provide the necessary reagents for analysis of immune function for use in cynomolgus macaque species. Cynomolgus macaques provide ideal models for infection with category A/B agents because they are both susceptible to infection with these agents and are readily available. However, some of the reagents required for evaluating the immune responses in this species are lacking. We propose to address these limitations by the following: 1. The MHC class I loci of cynomolgus macaques will be genetically characterized, and the loci found most common in the population identified. Peptide binding motifs specific for Category A agents will be further determined for use as reagents in T cell assays to better define and quantify the specificity of the immune response and to track effector populations to mucosal tissues. These studies will be performed through collaboration with scientists at the University of Pittsburgh and those at Epimmune, Inc. who have pioneered this effort in the rhesus macaque. 2. Cytokine/chemokine microarrays specific for cynomolgus macaques will be developed for evaluating pathogenic mechanisms and for analysis of immune responses to vaccines. 3. A primate model for mucosal vaccination using a Shigella dysenteriae challenge will be developed at the University of Maryland and characterized as a part of the above collaboration. Together, these efforts will provide an ideal setting with which to develop and test the methodologies proposed in this application.