Tickborne SFTS Virus Vaccine Development

蜱传 SFTS 病毒疫苗开发

• 批准号: 10670989
• 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/10670989
• 关键词: 4 year old; Age; Antibody Response; Asia; Attenuated; Attenuated Vaccines; Basic Science; Biochemical; CNR1 gene; Cells; Characteristics; Clinical; Communicable Diseases; DNA; DNA Vaccines; Dangerousness; Disease Outbreaks; Epidemic; Family; 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; Pathogenesis; Pathogenicity; Pathway interactions; Patients; Persons; Phosphotransferases; Production; Proteins; RNA; RNA-Directed RNA Polymerase; Recombinant Proteins; Recombinants; Risk Factors; Seroprevalences; Severe Fever with Thrombocytopenia Syndrome Virus; Source; Surface; Symptoms; Syndrome; System; T cell response; Testing; Thrombocytopenia; Ticks; Time; Vaccination; Vaccine Design; 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; clinical diagnosis; clinically relevant; comparative; gene function; immunogenicity; in vivo; insight; interferon alpha receptor; member; mortality; mouse model; mutant; nanobiotechnology; nanoparticle; neutralizing antibody; older patient; outbreak concern; pathogenic virus; protective efficacy; recombinant virus; reverse genetics; tick-borne; tool; vaccine candidate; vaccine development; vaccine efficacy; vector vaccine; 4 year old; Age; Antibody Response; Asia; Attenuated; Attenuated Vaccines; Basic Science; Biochemical; CNR1 gene; Cells; Characteristics; Clinical; Communicable Diseases; DNA; DNA Vaccines; Dangerousness; Disease Outbreaks; Epidemic; Family; 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; Pathogenesis; Pathogenicity; Pathway interactions; Patients; Persons; Phosphotransferases; Production; Proteins; RNA; RNA-Directed RNA Polymerase; Recombinant Proteins; Recombinants; Risk Factors; Seroprevalences; Severe Fever with Thrombocytopenia Syndrome Virus; Source; Surface; Symptoms; Syndrome; System; T cell response; Testing; Thrombocytopenia; Ticks; Time; Vaccination; Vaccine Design; 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; clinical diagnosis; clinically relevant; comparative; gene function; immunogenicity; in vivo; insight; interferon alpha receptor; member; mortality; mouse model; mutant; nanobiotechnology; nanoparticle; neutralizing antibody; older patient; outbreak concern; 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.

项目摘要/摘要 血小板减少综合征（SFTS）的严重发烧是新兴的tick传播 SFTS病毒（SFTSV）引起的传染病。 SFTSV在最危险的病毒中列出 在不久的将来，谁最有可能引起广泛流行病的病原体。发病率 SFTSV感染不断增加到5,000多人，死亡率 从12％到30％不等。 SFTSV诱导特征性血小板减少症 与病毒出血的发烧非常相似。受感染的壁虱是人类SFTSV的主要来源 感染。特别是，该票价最近传播到美国12个州的传播增加了潜力 对于远东地区以外的疾病爆发。 SFTSV在健康中的血清质量 年龄组之间的人没有显着差异，但是临床诊断的SFTS患者是 大于50岁以上，这表明年龄是SFTS发病率和死亡率的关键危险因素。 目前没有有效的疫苗可用于SFTSV。该提议的目的是 全面测试和比较四个SFTSV-的免疫原性和保护功效 在年龄依赖性雪貂模型中针对致命SFTSV感染的特异性疫苗候选物。