Development Of A Vaccine For Leishmania Major Infection

利什曼原虫感染在世界范围内引起显著的发病率和死亡率。感染宿主的利什曼原虫种类和宿主产生的免疫应答决定了所观察到的临床疾病谱。特别是，T细胞产生细胞因子的模式对于保护至关重要。目前还没有一种易于管理、有效且具有成本效益的利什曼原虫疫苗。这些实验将寻求建立一种疫苗方案，该方案足以在小鼠和灵长类动物感染性攻击后赋予长期保护性免疫力。实验将特别侧重于DNA、蛋白质和重组病毒疫苗。此外，这些研究将评估不同疫苗制剂诱导长期保护性细胞免疫的细胞和分子机制。在过去的一年里，我们确定了以下几点。 1. 抗原剂量和TLR佐剂（CpG）的量影响Th1应答的幅度和质量。 2. 来自三种不同疫苗的抗原特异性Th1应答的基因表达谱显示出显著差异，表明没有共同的基因组特征。

Infection with Leishmania causes significant morbidity and mortality worldwide. The type of Leishmania species infecting the host and the immune response generated by the host determines the spectrum of clinical disease that is seen. In particular, the pattern of cytokine production from T cells is critical for protection. At present there is no vaccine for Leishmania that is easy to administer, efficacious, and cost effective. These experiments will seek to establish a vaccine regimen that is sufficient to confer long-term protective immunity following infectious challenge in mice and primates. Experiments will specifically focus on DNA, protein and recombinant viral vaccines. In addition, these studies will evaluate the cellular and molecular mechanisms by which different vaccine formulations induce long-term protective cellular immunity. Over the past year we have determined the following. 1. Antigen dose and the amount of TLR adjuvant (CpG) influence the magnitude and quality of Th1 responses. 2. Gene expression profiling of antigen specific Th1 responses from three distinct vaccines that elicited protection showed striking differences suggesting there is not a common genomic signature.