VACCINE FOR CTL IMMUNITY IN HUMAN IMMUNODEFICIENCY VIRUS

描述：（改编自研究者摘要）研究者 一个广泛的目标是开发用于引发强CTL和CD 4 T的方法 使用蛋白质疫苗的HIV细胞反应。 的理由 重点是这些多重免疫反应应该给予 最强的保护。然而，理想的蛋白质免疫原 因为它们原则上比活疫苗更安全， CTL免疫可能是抗肿瘤最重要的免疫应答之一， 艾滋病。 此外，没有强佐剂（不能用于人类） 蛋白质免疫原通常仅引起弱的和短暂的CD 4依赖性免疫应答。 免疫力 在上一个资助期，研究人员假设 一种新的抗原呈递途径可以用来诱导CTL 蛋白质免疫反应。 他们的实验方法是 成功 在目前的更新中，他们将进一步发展这一点， approach. 他们有3个具体的目标：目标1：开发方法， 非活体（蛋白质）免疫原的CTL免疫。 第一个目标 目的之一是利用我们现有的技术开发一个子单元， 具有增强CTL免疫的HIV抗原的疫苗。 第二 目标是进一步发展这项技术， 最强的免疫反应。 这背后的假设是 第二个目的是更强的抗原呈递将导致 更强、更持久的免疫力。 一种实验方法将 通过增强抗原性修饰增加抗原性 呈递细胞摄取抗原的能力和抗原的速率 处理. 另一种方法将试图增加免疫原性 通过用细胞因子配制抗原构建体。 目标二： 开发方法以引发伴随的MHC I类和II类限制性 反应和粘膜免疫与蛋白质免疫原。 的假设 这一目标的基础是，最佳的抗病毒疫苗将需要 不仅引发CTL应答，而且引发CD 4 T细胞应答， 全身和粘膜免疫。 这个目标的目标是设计他们的 来自Aim 1的抗原制剂，使得它们引发II类MHC- 限制性应答（特别是Th 1）和粘膜免疫。 重要 目标是口服生物利用度和全身制剂， 不需要炎性佐剂。 目标3：评价疫苗 灵长类动物的策略 本目标的目的是评估和适应 他们诱导CTL和II类限制性免疫的方法 在灵长类动物中。 他们的实验方法是开发方法学， 测定我们的抗原构建体在灵长类APC中的活性。 一旦他们 鉴定活性制剂并优化其对灵长类动物效力 细胞，他们将测试他们在体内引发免疫反应的能力， 非人类灵长类动物

DESCRIPTION: (Adapted from investigator's abstract) The investigators broad objective is to develop methods for priming strong CTL and CD4 T cell responses to HIV using protein-based vaccines. The rationale for this focus is that these multiple immune responses should give the strongest protection. However, protein immunogens, which are desirable because they are in principle safer than live vaccines, fail to stimulate CTL immunity which may be one of the most important responses against HIV. Moreover, without strong adjuvants (which cannot be used in man) protein immunogens often elicit only weak and short-lived CD4-dependent immunity. In the previous funding period the investigators hypothesized that a novel antigen presenting pathway could be exploited to elicit CTL responses with protein immunogens. Their experimental approach was successful. In the present renewal, they will further develop this approach. They have 3 specific Aims: Aim 1: Develop methods to prime CTL immunity with non-living (protein) immunogens. The first objective of this Aim is to use our existing technology to develop a subunit vaccine with HIV antigens that elicits CTL immunity. The second objective is to further develop this technology so that it elicits the strongest possible immune response. The hypothesis underlying this second objective is that stronger antigen presentation will result in greater and longer lasting immunity. One experimental approach will increase antigenicity through modifications that enhance in antigen presenting cells that uptake of antigen and the rate of antigen processing. Another approach will attempt to increase immunogenicity through the formulation of antigen constructs with cytokines. Aim 2: Develop methods to prime concomitant MHC class I and II-restricted responses and mucosal immunity with protein immunogens. The hypothesis underlying this Aim is that optimal anti-viral vaccines will need to elicit not only CTL responses but also CD4 T cell responses and both systemic and mucosal immunity. The goal of this Aim is to engineer their antigen preparations from Aim 1 so that they elicit MHC class II- restricted responses (particularly Th1) and mucosal immunity. Important objectives will be oral bioavailability and systemic formulations that do not require inflammatory adjuvants. Aim 3: Evaluate vaccine strategies in primates. The goal of this Aim is to evaluate and adapt their methodologies for eliciting CTL and class II-restricted immunity in primates. Their experimental approach is to develop methodology to assay the activity of our antigen constructs in primate APCs. Once they identify active formulations and optimize their potency for primate cells, they will test their ability to elicit immune response in vivo in non-human primates.