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肉注射递送减毒病原体或其产品，由于疫苗运输、分发、管理和安全处置方面的后勤限制，这种方法会带来一些并发症。相比之下，表皮免疫（EPI）是一种令人兴奋的替代疫苗接种策略，涉及通过皮肤表面施用免疫原。虽然人们对这种新方法充满热情，但相对而言，人们对其在启动长期细胞介导的记忆反应方面的功效知之甚少，这些记忆反应能够对病原体产生保护性免疫。在这个建议中，我们将探索使用表皮免疫来启动能够控制小鼠各种病毒和细菌病原体的CDS T细胞反应。在Aim 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能够控制病原体的长寿命记忆T细胞。提高这种反应的能力也将在这里进行测试。在Aim 2中，我们关注的报告是，当小鼠暴露于不同的tlr时，当IL-12与1型干扰素不平衡时，对单核细胞增生李斯特菌的反应会发生根本改变。我们将探讨这可能如何限制使用表皮疫苗接种这种病原体。在Aim 3中，我们研究了紫外线照射对EPI的影响。众所周知，轻度晒伤可能发生的紫外线照射会抑制某些细胞免疫反应。我们将确定紫外线对表皮疫苗接种方法的抑制作用，以及如何控制这种抑制作用。

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.