Development of A HTLV-1 Vaccine

HTLV-1 疫苗的开发

• 批准号: 10209750
• 负责人: Glen N. Barber
• 金额: $ 62.37万
• 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/10209750
• 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; Lead; Lymphoproliferative Disorders; Malignant - descriptor; Malignant Neoplasms; Measures; Mediating; Middle East; Mus; Nerve Tissue; Nervous system structure; Oncolytic; Prevention; Production; 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; base; design; efficacy testing; experience; genetic regulatory protein; immunogenicity; in vivo; insight; leukemia/lymphoma; 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.

项目总结