Development of A HTLV-1 Vaccine

HTLV-1 疫苗的开发

• 批准号: 10582706
• 负责人: Glen N. Barber
• 金额: $ 58.37万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-03 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10582706
• 关键词: Adult T-Cell Leukemia/Lymphoma; Affect; Africa; Area; Attenuated; Australia; Binding; CD4 Positive T Lymphocytes; Caribbean region; Cell fusion; Cells; Clinical; Communities; Complement; Cytotoxic T-Lymphocytes; Development; Disease; Evaluation; Exhibits; Future; Giant Cells; Glycoproteins; Human; Human T-lymphotropic virus 1; Immune response; Immune system; Immunization; Immunocompetent; In Vitro; Individual; Infection; Inflammatory; Japan; Knowledge; Lymphoproliferative Disorders; Malignant - descriptor; Malignant Neoplasms; Measures; Mediating; Middle East; Mus; Nerve Tissue; Nervous System; Oncolytic; Persons; Predisposition; Prevention; Production; Proliferating; Proteins; Reporting; Retroviridae; South America; Spinal Cord Diseases; Symptoms; Taxes; Tertiary Protein Structure; Tropical Spastic Paraparesis; Tropism; United States; Vaccines; Vesicular stomatitis Indiana virus; Viral; Viral Proteins; Viral Vaccines; aged; bZIP Domain; design; efficacy testing; experience; genetic regulatory protein; immunogenicity; in vivo; insight; leukemia/lymphoma; manufacture; mouse model; mutant; neutralizing antibody; novel; novel vaccines; phase I trial; prevent; receptor; seropositive; tax Gene Products; therapeutic vaccine; transcription factor; vaccine candidate; vector; vector-based vaccine; Adult T-Cell Leukemia/Lymphoma; Affect; Africa; Area; Attenuated; Australia; Binding; CD4 Positive T Lymphocytes; Caribbean region; Cell fusion; Cells; Clinical; Communities; Complement; Cytotoxic T-Lymphocytes; Development; Disease; Evaluation; Exhibits; Future; Giant Cells; Glycoproteins; Human; Human T-lymphotropic virus 1; Immune response; Immune system; Immunization; Immunocompetent; In Vitro; Individual; Infection; Inflammatory; Japan; Knowledge; Lymphoproliferative Disorders; Malignant - descriptor; Malignant Neoplasms; Measures; Mediating; Middle East; Mus; Nerve Tissue; Nervous System; Oncolytic; Persons; Predisposition; Prevention; Production; Proliferating; Proteins; Reporting; Retroviridae; South America; Spinal Cord Diseases; Symptoms; Taxes; Tertiary Protein Structure; Tropical Spastic Paraparesis; Tropism; United States; Vaccines; Vesicular stomatitis Indiana virus; Viral; Viral Proteins; Viral Vaccines; aged; bZIP Domain; design; efficacy testing; experience; genetic regulatory protein; immunogenicity; in vivo; insight; leukemia/lymphoma; manufacture; mouse model; mutant; neutralizing antibody; novel; novel vaccines; phase I trial; prevent; receptor; seropositive; tax Gene Products; therapeutic vaccine; transcription factor; vaccine candidate; vector; vector-based vaccine

PROJECT SUMMARY For this proposal we intend to develop a novel vaccine to prevent and possibly treat Human T cell leukemia virus type-1 (HTLV-1) associated diseases. HTLV-1 is a human retrovirus that is the causative agent of a malignant T CD4+ cell lymphoproliferation referred to as Adult T cell leukemia/lymphoma (ATLL), as well as several inflammatory disorders with the most problematic being human myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1 infection is endemic in many areas around the world including southern Japan, the southern United States, central Australia, the Caribbean, South America, equatorial Africa, and the middle East. Over 10 million people may be infected worldwide. It is estimated that approximately 5% of HTLV-1 positive individuals will develop ATL, and 2% HAM/TSP. Seropositive rates in certain areas reach 20–40% among people aged over 50 years. With millions affected worldwide, HTLV-1 is a major problem in endemic communities and remarkably, there are no effective vaccine or treatment options to prevent ATL or HAM/TSP afflicted individuals. Given this, aim to develop and test the efficacy of a novel vaccine to prevent HTLV1-mediated disease. Aim 1: To evaluate the immunogenicity, in immunocompetent murine models, including mice with a humanized immune system (NSG™-SGM3) VSV-based vaccine vectors that express the HTLV-1 glycoprotein and regulatory proteins TAX and HBZ (VSV-gp62-∆HT). The ability of our candidate vaccine to generate neutralizing antibodies to the glycoprotein will be analyzed, as well as the production of cytotoxic T cells (CTLs) to gp62, TAX and HBZ. Aim 2: We aim to compare whether our vaccine can be used to prevent HTLV-1 transformation associated disease. This approach will include establishing whether VSV-gp62-∆HT can prevent the establishment of HTLV- 1-assocated leukemia/lymphoma in NSG™-SGM3 mice. Our objectives are to collate sufficient information to warrant the consideration of a variety of Phase I trials to prevent HTLV-1 -associated disease.

项目摘要 对于此提案，我们打算开发一种新型疫苗，以预防和可能治疗人类T细胞白血病 病毒类型1（HTLV-1）相关疾病。 HTLV-1是人类逆转录病毒，是A 恶性T CD4+细胞淋巴细胞增生称为成人T细胞白血病/淋巴瘤（ATLL），以及 几种炎症性疾病，最有问题的是人骨髓病/热带痉挛性副疾病 （HAM/TSP）。 HTLV-1感染在世界许多地区都是内在的，包括日本南部，南部 美国，澳大利亚中部，加勒比海，南美，非洲赤道和中东。超过10 百万人可能会被全世界感染。据估计，大约5％的HTLV-1阳性个体 将开发ATL和2％HAM/TSP。在某些地区的血清阳性率达到20–40％ 50年。由于全世界有数百万的影响，HTLV-1是内在社区的主要问题，非常明显 没有有效的疫苗或治疗选择可以防止ATL或HAM/TSP受苦的个体。给出 这是旨在开发和测试新型疫苗以防止HTLV1介导的疾病的效率。 目标1：在免疫能力的鼠模型中评估免疫原性，包括人源化的小鼠 免疫系统（NSG™-SGM3）基于VSV的疫苗向量，表达HTLV-1糖蛋白和 调节蛋白税和HBZ（VSV-GP62-∆HT）。我们候选疫苗产生中和的能力 将分析糖蛋白的抗体，以及细胞毒性T细胞（CTL）的产生，税收税，税收 和HBZ。 目标2：我们旨在比较是否可以使用疫苗来防止与HTLV-1转化相关 疾病。这种方法将包括确定VSV-GP62-∆HT是否可以防止建立HTLV- NSG™-SGM3小鼠中的1相关白血病/淋巴瘤。我们的目标是整理足够的信息 需要考虑各种I期试验，以防止与HTLV -1相关的疾病。