CORE--CLINICAL IMMUNOLOGY LABORATORY

疫苗已被证明是控制 传染病控制是通过限制复制来实现的 通过诱导抗原特异性免疫反应来对抗病原体。 特异性细胞毒性T淋巴细胞（CTL）应答是免疫应答的组成部分。 控制一些病毒感染。越来越多的调查人员 我认为，一种有效的HIV-1疫苗需要诱导一种 CTL应答。此外，产生强大和广泛的细胞和 体液反应似乎与维持 长期无进展者的无症状状态。最近，基于DNA 疫苗已经受到关注，用于开发针对 HIV-1我们已经证明了诱导体液和细胞 DNA疫苗在许多动物模型中的反应，包括 黑猩猩模型我们最近报道了关于保护黑猩猩 通过DNA疫苗的免疫预防HIV-1感染。虽然这 结果令人鼓舞，通过DNA免疫感染HIV-1 疫苗。虽然这一结果令人鼓舞，但免疫反应 HIV-1 DNA疫苗诱导的免疫应答需要进一步研究， 优化分子生物学的灵活性为我们提供了许多 寻求优化这些诱导免疫反应的途径。在 此外，免疫学的进步提供了几种技术来帮助 描述了DNA疫苗机制的重要细节- 诱导免疫应答并将应答与保护相关联。 该提案概述了一项旨在检查免疫系统的五年计划。 在两种动物模型中， 以及人类实验对象。该方案提出的五项原则 研究人员将致力于改进DNA免疫原的产生， 通过改造基因表达盒， 细胞因子以及其它免疫刺激基因序列。这个程序 将测试这种第二代疫苗对艾滋病毒的影响能力， 在动物、模型中复制，并调节HIV免疫应答。的 细胞免疫学核心的目标是确定 在黑猩猩和人类受试者中诱导的细胞反应的特征。 该核心设施将与项目1和2合作， 在猕猴研究中诱导的细胞反应的调查。 更具体地说，细胞免疫学核心将描绘CTL和 淋巴细胞增殖反应和免疫激活 第二代DNA疫苗的免疫接种，包括检测 交叉进化枝CTL活性。该核心还将尝试分析 不同细胞群以及细胞因子的激活 DNA质粒接种后诱导的图谱。这很可能 这将有助于世界范围内的发展。

Vaccines have proven to be the most effective agents for the control of infectious diseases. Control is accomplished by limiting the replication of pathogens through the induction of antigen specific immune responses. Specific cytotoxic T lymphocyte (CTL) responses are integral to the control of a number of viral infections. A growing number of investigators believe that an efficacious vaccine against HIV-1 will need to induce a CTL response. Furthermore, the generation of strong and broad cellular and humoral responses appear to correlate with the maintenance of the asymptomatic state in long-term non-progressors. Recently, DNA-based vaccines have received attention for the development of vaccines against HIV-1. We have demonstrated the induction of humoral and cellular responses by DNA vaccines in a number of animal models including the chimpanzee model. We recently reported on the protection of chimpanzees from infection with HIV-1 by immunization with DNA vaccines. Although this result is encouraging, the infection with HIV-1 by immunization with DNA vaccines. Although this result is encouraging, the immune responses induced by DNA vaccines against HIV-1 need to be further characterized and optimized. The flexibility of molecular biology affords us a number of avenues to pursue in optimizing these induced immune responses. In addition, immunologic advances provide several techniques to aid in characterizing important details about the mechanism of DNA vaccine- induced immune responses and correlating the responses with protection. This proposal outlines a five year plan designed to examine the immune responses induced by DNA vaccines against HIV-1 in both animal models as well as human subjects. The program proposed by the five principle investigators will focus on the generation of improved DNA immunogens through engineering gene expression cassettes which will co-deliver cytokines as well as other immunostimulatory gene sequences. This program will test the ability of such second generation vaccines to impact on HIV replication in animals, models and to modulate HIV immune responses. The goal of the cellular immunology core is to determine the magnitude and character of cellular responses induced in chimpanzee and human subjects. This core facility will collaborate with Projects 1 and 2 to aid in the investigation of the cellular responses induced in the macaque studies. More specifically, the cellular immunology core will delineate CTL and lymphocyte proliferative responses, and the immune activation following immunization with second generation DNA vaccines including testing for cross-clade CTL activity. This core will also attempt to profile the activation of the different cellular populations as well as the cytokine profiles induced following DNA plasmid vaccination. It is likely that this will aid in the development for world wide distribution.