Vaccine Prevention of Rheumatic Fever

风湿热疫苗预防

• 批准号: 7113104
• 负责人: JAMES B. DALE
• 金额: $ 50.97万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7113104
• 关键词: Africa; Central America; Streptococcus pyogenes; Streptococcus vaccine; clinical research; clinical trial phase I; cooperative study; cytokine; disease /disorder model; disease /disorder prevention /control; drug administration routes; helper T lymphocyte; human subject; laboratory mouse; microorganism population study; patient oriented research; pharyngitis; rheumatic fever; vaccine development

The overall goal of this project is to develop a safe and effective multivalent M protein-base d vaccine to prevent acute rheumatic fever (ARF). Rheumatic fever is triggered by group A streptococcal infections of the throat. Although the incidence of ARF has declined markedly in the U.S. and other developed countries over the past 50 years, the disease remains rampant in developing countries of the world. Rheumatic heart disease (RHD) is the leading cause of heart disease in children throughout the world. An estimated 12 million people suffer from chronic RHD and 400,000 die from the disease each year. Thus, the development of an effective vaccine designed to prevent the streptococcal infections that cause ARF and RHD could significantly improve the health of millions of children around the world. The aims of this proposal are: 1) To determine the distribution of group A streptococcal serotypes causing acute pharyngitis in countries where ARF is common, 2) to determine the optimal formulation and route of delivery of multivalent group A streptococcal vaccines using an established mouse model, 3) to identify T cell epitopes within multivalent vaccines in order to enhance the overall protective antibody responses to the multivalent vaccines, 4) to translate these findings into the design, construction, GMP production, and formulation of a multivalent vaccine to prevent rheumatic fever, and 5) to perform a phase I clinical trial to assess the safety and immunogenicity of the vaccine in adult volunteers. Prospective studies will be conducted in Mall, West Africa and Leon, Nicaragua to identify the prevalent rheumatogenic serotypes. This information will be combined with available data on the emm-type distribution of clinical isolates from around the world. Laboratory studies in animals will establish the optimal formulation and route of delivery for the vaccine. The final vaccine will be produced and manufactured to GMP standards by ID Biomedical Corporation. The proposed phase I clinical trial will be performed at the University of Maryland and will establish the safety and immunogenicity of the vaccine in human adult volunteers. Successful completion of these studies will bring us one step closer to determining whether acute rheumatic fever is a vaccine preventable disease.

该项目的总体目标是开发一种安全有效的基于M蛋白的多价d疫苗来预防急性风湿热（ARF）。风湿热是由喉咙 A 族链球菌感染引发的。尽管过去50年来ARF的发病率在美国和其他发达国家明显下降，但该病在世界发展中国家仍然猖獗。风湿性心脏病（RHD）是全世界儿童心脏病的主要原因。据估计，每年有 1200 万人患有慢性 RHD，其中 40 万人死于该病。因此，开发一种有效的疫苗来预防引起 ARF 和 RHD 的链球菌感染可以显着改善全世界数百万儿童的健康。该提案的目的是： 1) 确定在 ARF 常见的国家中引起急性咽炎的 A 组链球菌血清型的分布，2) 使用已建立的小鼠模型确定多价 A 组链球菌疫苗的最佳配方和给药途径，3) 识别多价疫苗内的 T 细胞表位，以增强对多价疫苗的整体保护性抗体反应，4) 将这些发现转化为 设计、构建、GMP 生产和配制预防风湿热的多价疫苗，以及 5) 进行 I 期临床试验，以评估疫苗在成年志愿者中的安全性和免疫原性。前瞻性研究将在西非马尔进行 和尼加拉瓜莱昂以确定流行的风湿性血清型。该信息将与世界各地临床分离株的 emm 型分布的现有数据相结合。动物实验室研究将确定疫苗的最佳配方和给药途径。最终疫苗将由 ID Biomedical Corporation 按照 GMP 标准生产和制造。拟议的一期临床试验将在马里兰大学进行，并将确定疫苗在成人志愿者中的安全性和免疫原性。这些研究的成功完成将使我们更接近确定急性风湿热是否是一种疫苗可预防的疾病。