De Novo Induction of Simian CTL Using Lentivirus Vectors

描述：（由申请人提供）HIV疫苗必须针对引发 强病毒特异性T细胞反应，以控制HIV感染细胞 在爆发性病毒产生之前。对于任何候选疫苗 对于艾滋病病毒，主要的目标必须是树突状细胞，因为它们发挥着重要作用。 在向初始T细胞呈递抗原和诱导免疫应答中的中心作用 主要的细胞免疫反应。能够稳定地 在原代非增殖细胞中整合和表达所需基因， 树突状细胞的潜在疫苗输送系统。我们将确定 树突状细胞是否稳定表达慢病毒基因产物， 慢病毒载体有效地引发保护性抗病毒免疫应答。 为此，我们将使用恒河猴作为动物模型， 我们的疫苗研究首先，我们将优化必要的条件， 慢病毒载体在单核细胞来源的细胞中稳定表达SIV基因， 来自恒河猴的树突状细胞。我们将评估树突状细胞是否 SIV基因转导的细胞迁移到引流淋巴组织， 增加了它们与SIV特异性细胞毒相互作用的可能性， T淋巴细胞（CTL）前体。接下来我们将确定恒河猴 注射转导的细胞在体内产生抗SIV CTL。最后我们 将研究是否由转导的树突状细胞产生的免疫力， 动物提供保护以抵抗感染性SIV的攻击。结果 这些灵长类动物的研究将为开发靶点提供重要信息。 预防艾滋病毒的疫苗。

DESCRIPTION: (Provided by Applicant) HIV vaccines must be directed at eliciting strong virus specific T-cell responses in order to control HIV-infected cells before the development of fulminant virus production. For any candidate vaccine for HIV, the principal targets must be dendritic cells, since they play a central role in the presentation of antigens to naive T-cells and the induction of primary cellular immune responses. Lentivirus vectors capable of stably integrating and expressing a desired gene in primary nonproliferating cells are potential vaccine delivery systems for dendritic cells. We will determine whether dendritic cells, made to stably express lentivirus gene products with lentivirus vectors, efficiently elicit protective anti-viral immune responses. Toward this objective, we will use the rhesus macaque as an animal model for our vaccine studies. Initially, we will optimize the conditions necessary for the lentivirus vectors to stably express SIV genes in monocyte-derived dendritic cells from rhesus macaques. We will evaluate whether dendritic cells transduced with SIV genes migrate to draining lymphoid tissues, thereby increasing their likelihood of interacting with SIV-specific cytotoxic T-lymphocyte (CTL) precursors. We will determine next if rhesus macaques injected with the transduced cells generate anti-SIV CTL in vivo. Finally, we will investigate if the immunity generated by the transduced dendritic cells in animals provides protection against challenge with infectious SIV. Results from these primate studies will provide important information in developing target vaccines against HIV.