Vaccine Prevention of Rheumatic Fever

风湿热疫苗预防

基本信息

批准号：
7490667
负责人：
JAMES B. DALE
金额：
$ 47.06万
依托单位：
UNIVERSITY OF TENNESSEE HEALTH SCI CTR
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-09-01 至 2011-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7490667
关键词：
Academia Acute Acute Pharyngitis Address Adjuvant Adult Africa Animals Antibodies Antibody Formation Antigens Biological Assay Cells Centers for Disease Control and Prevention (U.S.)Cervical lymph node group Child Chronic Clinical Distribution Clinical Research Combined Vaccines Consensus Country DNA Data Developed Countries Developing Countries Development Disease Dose Drug Formulations Enzyme-Linked Immunosorbent Assay Epidemiology Facility Construction Funding Category Funding Genes Goals Guanosine Monophosphate Health Heart Diseases Immune response In Vitro Incidence Individual Industry Infection Intramuscular Laboratory Study Lipid A Liposomes Lymphocyte Activation Maryland Medical Surveillance Mononuclear Mus Nicaragua North America One-Step dentin bonding system Peptides Pharyngeal structure Pharyngitis Phase Phase I Clinical Trials Plasmids Prevalence Prevention Production Prospective Studies Proteins Protocols documentation Publishing Recombinant Vaccines Recombinants Reporting Research Research Personnel Rheumatic Fever Rheumatic Heart Disease Route Safety Saliva Schedule Selection Criteria Serotyping Serum Site Source Spleen Standards of Weights and Measures Streptococcal Infections Streptococcal Vaccines Streptococcus Streptococcus pyogenes Subunit Vaccines T-Lymphocyte T-Lymphocyte Epitopes Testing Toxic effect Translating Universities Upper arm Vaccine Design Vaccines Western Europe Work aluminum sulfate base cytokine design design and construction enzyme linked immunospot assay experience immunogenic immunogenicity improved intraperitoneal lymph nodes member mouse model multicatalytic endopeptidase complex multiple myeloma M Protein novel vaccines preclinical study prevent programs prototype recombinant peptide research clinical testing research study response vaccine delivery vaccine efficacy volunteer

项目摘要

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多价M蛋白碱D疫苗，以防止急性风湿热（ARF）。风湿热是由A组的喉咙链球菌感染引起的。尽管在过去50年中，美国和其他发达国家的ARF发生率显着下降，但在世界发展中国家中，该疾病仍然猖ramp。风湿性心脏病（RHD）是全世界儿童心脏病的主要原因。估计每年有1200万人患有慢性RHD和40万人死亡。因此，开发旨在防止引起ARF和RHD的链球菌感染的有效疫苗可以显着改善世界上数百万儿童的健康。该提议的目的是：1）确定A组链球菌血清型的分布，在ARF很常见的国家中引起急性咽炎，2）确定多价组A链球菌疫苗的最佳配方和途径，使用已建立的小鼠模型，3），以鉴定多价疫苗，以增强跨性别抗体反应，以增强综合抗体反应，以增强量的抗体反应。设计，建筑，GMP的生产和多价疫苗的制剂以防止风湿发烧，以及5）进行I期临床试验，以评估成人志愿者中疫苗的安全性和免疫原性。前瞻性研究将在西非购物中心进行尼加拉瓜莱昂（Leon），以识别流变的风湿性血清型。该信息将与有关来自世界各地的临床分离株的EMM型分布的可用数据结合使用。动物的实验室研究将建立疫苗的最佳配方和输送途径。最终的疫苗将由ID Biomedical Corporation生产和制造，按GMP标准生产。拟议的I期临床试验将在马里兰大学进行，并将在人类成人志愿者中建立疫苗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可预防的疾病。