Transmitted/Founder SHIV macaque model

传播/创始人SHIV猕猴模型

• 批准号: 9204007
• 负责人: Siddappa N Byrareddy
• 金额: $ 18.81万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-24 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9204007
• 关键词: Transmitted; Founder; SHIV; macaque; model

DESCRIPTION (provided by applicant): Several substantial vaccine efforts against HIV-1 have so far failed primarily because to date we have failed to identify the correlates of protectiv immunity and the optimal vaccine formulation that can induce such protective immune responses in vivo. The knowledge that only select single or limited virus species are transmitted via the mucosal route has advanced the concept of Transmitter/Founder viruses (T/F). It is reasoned that such viruses that are preferentially transmitted should be the target of HIV vaccine efforts. The clade 'C' viruses that constitute the major clade transmitted sexually worldwide therefore have become the focus of studies for vaccine formulations. However, there is a lack of both suitable clade 'C' viruses and an optimal nonhuman primate model that faithfully mimics such natural transmission so that it can be utilized for the testing of candidate vaccines or microbicides. The present proposal is directed at providing the initial foundation for these objectives. Our lab has available unique pairs of infectious molecular clones (IMC) of replication competent T/F viruses from heterosexual transmission studies being conducted in Rwanda-Zambia. Our lab has prepared and tested a number of SHIVs in the past and is thus highly experienced to exploit these unique sets of T/F cloned viruses and prepare in vitro and in vivo replication competent clade C T/F env-SHIVs which will share all the properties required for the testing of candidate vaccines. We plan to carry out systematic studies that include 1) the derivation and the detailed in vitro characterization of such recombinant SHIVs using a battery of tests 2) To utilize novel in vivo cell lineage depletion techniques that our lab has optimized i rhesus macaques and attempt to adapt the SHIVs for efficient replication in such models leading to the isolation of swarms of SHIVs stocks and 3) to test such in vitro and in vivo replication competent swarms of SHIV's for mucosal transmission. We submit that we are uniquely poised in terms of reagents, talent, experience and knowledge to achieve the objectives outlined in this proposal.

描述（由申请人提供）：到目前为止，针对HIV-1的几项实质性疫苗的努力主要是因为迄今为止我们未能识别保护免疫的相关性和最佳的疫苗配方，可以在体内诱导这种保护性免疫反应。通过粘膜途径传播只有选择单一或有限病毒物种的知识已经提出了发射机/创始人病毒（T/F）的概念。有理由认为，优先传播的这种病毒应该是HIV疫苗努力的目标。因此，构成全球性行为主要进化枝的进化枝“ C”病毒已成为疫苗配方研究的重点。但是，缺乏合适的进化枝“ C”病毒和最佳的非人类灵长类动物模型，该模型忠实地模仿了这种自然传播，因此可以用于测试候选疫苗或杀生型。目前的建议旨在为这些目标提供最初的基础。我们的实验室拥有在卢旺达 - 桑比亚进行的异性传播研究中可复制的独特的感染分子克隆（IMC）。我们的实验室过去曾准备好并测试了许多SHIV，因此经验丰富，可以利用这些独特的T/F克隆病毒集，并在体外和体外复制效果促进甲板C t/f envivs进行准备，这些进化枝C T/F env-Shivs将共享所有测试候选疫苗所需的所有属性。我们计划进行系统研究，包括1）使用一系列测试的衍生和详细的体外表征和详细的体外表征2）利用新颖的体内细胞谱系耗尽技术，我们的实验室已经优化了我的鼻误痕，并试图在shivs中进行有效的模型，以使Swarm在Swarm中有效地进行了swarms的隔离，并试图在Swarm上进行隔离，并试图在Swarm上进行隔离。以及湿婆的粘膜传播的体内复制群体。我们认为，我们在试剂，人才，经验和知识方面都有独特的准备，以实现该提案中概述的目标。