Developing epicutaneous vaccine approaches for protective immunity

描述（由申请人提供）：预防传染病的疫苗接种仍然是公共卫生的一个重要和具有成本效益的目标。典型的免疫策略包括通过肌内注射递送减毒病原体或其产物，这种方法由于疫苗运输、分配、施用和安全处置中的物流限制而引入许多并发症。相比之下，表皮免疫（EPI），涉及通过皮肤上的表面应用程序提供的免疫原，提供了一个令人兴奋的替代疫苗接种策略。虽然对这种新方法有很大的热情，但对其在引发能够对病原体产生保护性免疫的长寿命细胞介导的记忆反应方面的功效知之甚少。在这个提议中，我们将探索使用表皮免疫来引发CDS T细胞反应，从而能够控制小鼠中的各种病毒和细菌病原体。在目标1中，我们将测试各种Toll样受体（TLR）对EPI的影响，特别强调表皮启动是否诱导长寿的记忆T细胞，能够控制病原体。加强这种反应的能力也将在这里受到考验。在目标2中，我们关注的报道是，当小鼠暴露于不同的TLR时，以及当IL-12与I型干扰素不平衡时，对病原体单核细胞增生李斯特菌的反应发生根本性改变。我们将探讨这可能如何限制这种病原体的表皮接种的使用。目的3研究了紫外线照射对EPI的影响。紫外线照射，可能会发生轻微的晒伤，是已知的抑制一些细胞免疫反应。我们将确定紫外线对表皮接种方法的抑制作用，以及如何控制。

DESCRIPTION (provided by applicant): Vaccination against infectious diseases remains an important and cost-effective goal for public health. Typical immunization strategies involve delivery of attenuated pathogens or their products via intramuscular injections an approach which introduces a number of complications due to logistic limitations in vaccine transportation, distribution, administration and safe disposal. In contrast, epicutaneous immunization (EPI), involving immunogens delivered via surface application on the skin, offers an exciting alternative vaccination strategy. While there is much enthusiasm for this novel approach, relatively little is known about its efficacy at priming long-lived cell-mediated memory responses capable of protective immunity to pathogens. In this proposal, we will explore the use of epicutaneous immunization to prime CDS T cell responses capable of controlling various viral and bacterial pathogens in mice. In Aim 1, we will test the impact of various Toll-like receptors (TLR) on EPI, with a special emphasis on whether epicutaneous priming induces long lived memory T cells, capable of controlling pathogens. The ability to boost this response will also be tested here. In Aim 2, we focus on reports that the response to the pathogen Listeria monocytogenes is radically altered when mice are exposed to different TLRs, and when there is an imbalance of IL-12 versus Type-l Interferons. We will explore how this might limit the use of epicutaneous vaccination for this pathogen. In Aim 3, we study the effects of UV irradiation on EPI. UV irradiation, as might occur with mild sunburn, is known to suppress some cellular immune responses. We will determine what inhibitory effect UV has on epicutaneous vaccination approaches, and how this can be controlled.