Tickborne SFTS Virus Vaccine Development

蜱传 SFTS 病毒疫苗开发

• 批准号: 10227961
• 负责人: Jae U Jung
• 金额: $ 56.45万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-03 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10227961
• 关键词: 4 year old; Age; Antibody Response; Attenuated; Attenuated Vaccines; Basic Science; Biochemical; CNR1 gene; Cells; Characteristics; Clinical; Communicable Diseases; DNA; DNA Vaccines; Dangerousness; Disease Outbreaks; Epidemic; Far East; Ferrets; Ferritin; Fever; Future; Genes; Genetic; Genome; Genotype; Genus Phlebovirus; Glycoproteins; Goals; Head; Hemorrhage; Host Defense; Human; IFNAR1 gene; Immune; Immune Evasion; Immunity; Immunocompetent; Immunologics; Incidence; Infection; Interleukin-10; MAP3K8 gene; Modeling; Molecular; Morbidity - disease rate; Mus; Nanotechnology; Nonstructural Protein; Pathogenesis; Pathogenicity; Pathway interactions; Patients; Phosphotransferases; Production; Proteins; RNA; RNA-Directed RNA Polymerase; Recombinants; Risk Factors; Seroprevalences; Severe Fever with Thrombocytopenia Syndrome Virus; Source; Structure; Surface; Symptoms; Syndrome; System; T cell response; Testing; Thrombocytopenia; Ticks; Time; Vaccination; Vaccines; Vesicular stomatitis Indiana virus; Viral; Viral Genes; Viral Genome; Viral Hemorrhagic Fevers; Viral Pathogenesis; Viral Proteins; Virion; Virus; Virus Diseases; Virus Replication; age group; age related; aged; base; clinical Diagnosis; clinically relevant; comparative; gene function; immunogenicity; insight; member; mortality; mouse model; mutant; nanoparticle; neutralizing antibody; older patient; pathogenic virus; protective efficacy; recombinant virus; reverse genetics; tick-borne; tool; vaccine candidate; vaccine development; vaccine efficacy; vector vaccine

Project Summary/Abstract Severe fever with thrombocytopenia syndrome (SFTS) is a newly emerging tick-borne infectious disease caused by SFTS virus (SFTSV). SFTSV is listed in the most dangerous viral pathogens by the WHO that most likely cause wide epidemics in the near future. The incidence of SFTSV infection has continuously increased up to more than 5,000 humans with a mortality rate ranging from 12% to as high as 30%. SFTSV induces a characteristic thrombocytopenia that is remarkably similar to viral hemorrhagic fevers. Infected ticks are the major source of human SFTSV infection. Particularly, the recent spread of this tick to over 12 states of USA increases the potential for outbreaks of the disease beyond the Far East Asia. The sero-prevalence of SFTSV in healthy people is not significantly different among age groups, but clinically diagnosed SFTS patients are older than ~50 years, suggesting that age is the critical risk factor for SFTS morbidity and mortality. No effective vaccines are currently available for SFTSV. The goal of this proposal is to comprehensively test and compare the immunogenicity and protection efficacy of four SFTSV- specific vaccine candidates against lethal SFTSV infection in age-dependent ferret model.

项目概要/摘要 严重发烧伴血小板减少综合征（SFTS）是一种新出现的蜱传疾病 由 SFTS 病毒 (SFTSV) 引起的传染病。 SFTSV 被列为最危险的病毒 世界卫生组织认为最有可能在不久的将来引起广泛流行的病原体。发病率 SFTSV感染持续增加，致死人数已达5000多人 从 12% 到高达 30% 不等。 SFTSV 会诱发特征性血小板减少症，即 与病毒性出血热非常相似。受感染的蜱是人类SFTSV的主要来源 感染。特别是，这种蜱虫最近蔓延到美国超过 12 个州，增加了潜在的可能性 该疾病在远东亚洲以外地区的爆发。健康人中SFTSV的血清流行率 人们在不同年龄组之间没有显着差异，但临床诊断的 SFTS 患者 年龄超过 50 岁，表明年龄是 SFTS 发病率和死亡率的关键危险因素。 目前尚无针对 SFTSV 的有效疫苗。该提案的目标是 全面测试并比较四种SFTSV的免疫原性和防护功效 在年龄依赖性雪貂模型中针对致命性 SFTSV 感染的特定候选疫苗。