Development Of A Vaccine For Leishmania Major Infection

开发利什曼原虫重大感染疫苗

• 批准号: 7964815
• 负责人: ROBERT A SEDER
• 金额: $ 164.19万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7964815
• 关键词: Activities of Daily Living; Adenoviruses; Adjuvant; Antibodies; Antibody Formation; Antigens; Autoimmune Diseases; CD4 Positive T Lymphocytes; CD8B1 gene; Cellular Immunity; Cellular Immunology; Clinical; DNA; Development; Disease; Dose; Drug Formulations; Enhancing Antibodies; Equilibrium; Flow Cytometry; Frequencies; Generations; HIV; Human; Immune response; Immunity; Immunization; Infection; Interferon Type II; Interferons; Interleukin-10; Leishmania; Leishmania major; Maintenance; Malaria; Mediating; Modeling; Molecular; Morbidity - disease rate; Mus; Mycobacterium tuberculosis; Organ; Pattern; Play; Primates; Production; Proteins; Role; T-Lymphocyte; Th1 Cells; Th2 Cells; Treatment Protocols; Vaccination; Vaccines; base; cost effective; cytokine; improved; killings; mortality; pathogen; recombinant virus vaccine; research study; response; vaccine development

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.

利什曼原虫感染在全世界范围内造成显着的发病率和死亡率。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临床疾病的范围。特别是，T 细胞产生细胞因子的模式对于保护至关重要。目前尚无易于施用、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，足以在小鼠和灵长类动物遭受感染攻击后赋予长期保护性免疫力。实验将特别关注 DNA、蛋白质和重组病毒疫苗。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，我们确定了以下内容。 1. IL-10 影响蛋白质+ CpG 免疫后 Th1 反应的程度和质量。 2.编码利什曼原虫抗原的5型腺病毒免疫在有或没有IFN-g的情况下诱导高频率产生IL-10的CD4+T细胞。 3. rAd-5 免疫后 CD4+ T 细胞产生的 IL-10 不会改善疫苗产生的 Th1 反应的保护作用。 4.抗原剂量和TLR佐剂(CpG)的量影响Th1反应的幅度和质量。