Stimulation of DNA vaccines by IRF

描述(申请人提供)：这些研究的长期目的是确定干扰素调节因子家族(IRF)的转录因子在免疫反应中的作用。这一应用的重点是阐明IRF增强DNA诱导的免疫应答的分子机制。在过去的几年里，我们已经鉴定并鉴定了三个新的红外线受体：IRF-3、IRF-5和IRF-7。这些IRF作为病毒诱导信号的直接转导因子，在早期炎症基因的诱导中起着关键作用。然而，它们的功能超越了天然免疫，我们已经确认IRF-7是一种巨噬细胞分化因子。此外，IRF-1、IRF-3或IRF-7的表达可增强DNA增强的免疫应答。在这项研究中，我们希望研究IRF对流感病毒血凝素蛋白和HIV-1包膜蛋白这两种病毒抗原对DNA介导的免疫应答的佐剂作用的分子基础。为此，本研究有三个目的，我们将在其中提出以下问题：目的1.IRF对两种不同抗原的免疫应答的佐剂作用是否相同？我们将分析对HIV-1的GP 160的体液和细胞反应，并将其与流感对HA的反应进行比较。目的#2.IRF是否由I型干扰素介导的佐剂作用？IRF被证明能刺激I型干扰素的诱导，因此我们将研究IRF在缺乏I型干扰素受体的小鼠中的佐剂作用。为了进行比较，将检测共表达IFNA对DNA增强的免疫应答的影响。目的#3.在佐剂效应中是否需要激活IRF？我们将研究组成活性的IRF-3和RF-7对DNA介导的免疫反应的佐剂作用。意义：与传统疫苗相比，DNA介导的疫苗提供了强大的病毒特异性CD4+和CD8+反应，这对控制包括HIV-1在内的许多病毒感染的病毒血症至关重要，而且它的分发将是容易和经济的。因此，开发有效的DNA佐剂诱导免疫应答具有重要的流行病学和经济意义。

DESCRIPTION (provided by applicant): The long term of these studies is to determine the role of transcription factors of the interferon regulatory factor family (IRF) in immune responses. This application is focused on the clarification of molecular mechanism by which IRF enhance the DNA raised immune response. Over the past years we have identified and characterized three novel IRFs: IRF-3, IRF-5 and IRF-7. These IRF functions as direct transducers of virus induced signaling and play a critical role in induction of the early inflammatory genes. However, their function extends beyond innate immunity and we have identify IRF-7 as a macrophage differentiation factor. Furthermore the expression of IRF-1, IRF-3 or IRF-7 enhances a DNA raised immune response. In the proposed study we wish to examine the molecular basis of the adjuvant effect of IRF on DNA mediated immune response by two viral antigens, hemaglutinin protein of influenza virus and envelope protein of HIV-1. To this effect the study has three Aims in which we shall ask following questions: Aim#1. Is the adjuvant effect of IRF on immune response to two distinct antigens identical? We shall analyzed humeral and cellular response to gp 160 of HIV-1 and compare it with the response to HA of influenza. Aim #2. Is the adjuvant effect of IRF mediated by Type I IFN? The IRF were shown to stimulate induction of Type I IFN we shall therefore examine the adjuvant effect of IRF in mice that is lacking the Type I IFN receptor. Effect of co-expression of IFNa on DNA raised immune response will be examined for comparison. Aim #3. Is there a requirement for IRF activation in the adjuvant effect? We shall examine the adjuvant effect of constitutively active IRF-3 and !RF-7 on a profile of DNA mediate immune responses. Significance: Compared to the conventional vaccines, the DNA mediated vaccination provides elicits potent virus specific CD4+ and CD8+ responses that are critical for controlling viremia in many viral infections including HIV-1 and its distribution would be easy and economical. Thus the development of potent adjuvant of DNA elicited immune response is of great epidemiological and economical importance.