Development Of A Vaccine For Leishmania Major Infection

利什曼原虫感染在世界范围内导致严重的发病率和死亡率。感染宿主的利什曼原虫种类和宿主产生的免疫反应决定了所见临床疾病的谱系。特别是，T细胞产生细胞因子的模式对保护至关重要。目前还没有一种易于管理、有效且成本效益高的利什曼病疫苗。这些实验将寻求建立一种疫苗方案，足以在小鼠和灵长类动物受到感染攻击后提供长期保护性免疫。实验将专门集中在DNA、蛋白质和重组病毒疫苗上。此外，这些研究将评估不同疫苗配方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.IL-10影响蛋白质+CpG免疫后Th1应答的大小和质量。 2.编码利什曼病毒抗原的5型腺病毒免疫小鼠可诱导高频率的产生IL-10的CD4+T细胞，无论是否有干扰素-g。 3.Rad-5免疫后由CD4+T细胞产生的IL-10不能通过疫苗产生的Th1反应来增强保护作用。 4.抗原剂量和TLR佐剂用量(CpG)影响Th1应答的大小和质量。

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. IL-10 influences the magnitude and quality of Th1 responses following protein+ CpG immunization. 2. Adenovirus Type 5 immunization encoding a leishmanial antigen induces a high frequency of IL-10 producing CD4+ T cells with or without IFN-g. 3. IL-10 produced by CD4+ T cells following rAd-5 immunization does not improve protection by Th1 responses generated by the vaccine. 4. Antigen dose and the amount of TLR adjuvant (CpG) influence the magnitude and quality of Th1 responses.