Age in dengue antibody response and risk after primary natural infection

登革热抗体反应的年龄和初次自然感染后的风险

• 批准号: 10661564
• 负责人: Deanna Zhu
• 金额: $ 3.97万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10661564
• 关键词: 11 year old; 5 year old; 9 year old; Affect; Age; Americas; Antibodies; Antibody Avidity; Antibody Response; Antibody Specificity; Antigen-Antibody Complex; Attenuated; Attenuated Vaccines; Binding; Cells; Child; Childhood; Chimera organism; Cohort Studies; Complex; Country; Cross Reactions; Data; Data Set; Dengue; Dengue Hemorrhagic Fever; Dengue Infection; Dengue Shock Syndrome; Dengue Vaccine; Dengue Virus; Dengvaxia; Development; Disease; Disease Outbreaks; Doctor of Philosophy; E protein; Engineering; Enrollment; Ensure; Epidemiologic Methods; Epidemiology; Epitopes; Event; Exclusion; Fellowship; Fever; Filipino; Future; Genotype; Glycoproteins; Health; Hospitalization; Human; Immune response; Immunity; Immunize; Immunologics; Immunology; Incidence; Individual; Infection; Infectious Disease Epidemiology; Intervention; Latin American; Life; Longitudinal Studies; Longitudinal, observational study; Measles; Mediation; Mentors; Methods; Monitor; Monoclonal Antibodies; Nicaragua; North Carolina; Outcome; Parents; Pathogenesis; Pattern; Philippines; Physicians; Policies; Population; Primary Infection; Production; Recombinants; Recording of previous events; Research; Risk; Risk Assessment; Role; Safety; Sampling; Schools; Scientist; Serology; Serotyping; Serum; Specificity; Techniques; Time; Training; Travel; Universities; Vaccinated; Vaccination; Vaccines; Variant; Viral; Virus; Yellow Fever; age group; breakthrough infection; cohort; cross reactivity; domain mapping; follow-up; global temperature; human monoclonal antibodies; improved; infection risk; neutralizing antibody; phase III trial; population health; recombinant virus; response; skills; vaccine acceptance; vaccine development; vaccine efficacy; vaccine safety; vector; vector-borne; virology; virus envelope

PROJECT SUMMARY/ABSTRACT Dengue is the most prevalent vector-borne virus plaguing our world. In 2010, there were an estimated 390 million infections worldwide, 25% of which were symptomatic. The pathogenesis of dengue is complex because of the existence of four serotypes. Infection with one serotype protects the individual against future infections of the same serotype, but subsequent infection with a different serotype increases the risk of symptomatic disease, which includes potentially life-threatening dengue hemorrhagic fever and dengue shock syndrome. In endemic countries, children are most at risk of infection and disease. An immunizing vaccine is crucial for population protection but large trials of live-attenuated vaccine in children show that younger age is associated with future infection and severe disease independent of other variables. Vaccination is a correlate to natural infection, where in previously unexposed individuals, antibodies that cross-react to many serotypes protect against multiple dengue serotypes but are short-lived. Long-lasting protection most likely comes from a small fraction of durable antibodies that are specific to one dengue serotype. What determines the production of these type-specific antibodies and the viral epitopes that they target is not well understood. Immunologic studies incorporating longitudinal observational data are needed to understand protective antibody responses after primary natural dengue infection in children. This study will address relationships between age, antibody quality, and dengue infection or disease. The proposed research will utilize previously collected data and sera from an ongoing longitudinal observational study, the Pediatric Dengue Cohort Study in Managua, Nicaragua. Using state-of-the-art recombinant viral techniques and epidemiologic methods in this one-of-a-kind dataset, the proposal aims to 1) compare how epitopes targeted by antibodies vary in younger and older children with known dengue serotype 2 infection and 2) assess the risk of dengue reinfection in younger and older children with prior natural dengue infection. The results will establish the variation in antibody specificity and avidity in younger and older children and inform future policy decisions regarding vaccination against dengue virus in this population and possibly other Latin American countries. Through the completion of these research aims the trainee will gain a unique set of skills in advanced epidemiologic methods, virology, and immunology research, including analysis and interpretation of complex immunologic and longitudinal data. Expert mentors in virology, immunology, and epidemiology will support the trainee’s successful completion of the proposed research, associated training plan, and MD/PhD degree at the University of North Carolina at Chapel Hill. This F30 fellowship will critically aid the applicant’s development as a future interdisciplinary physician-scientist practicing at the intersection of virology, immunology, and infectious disease epidemiology.

项目摘要/摘要 登革热是困扰我们世界的最普遍的媒介传播病毒。在2010年，估计有390 全世界有百万个感染，其中25％是有症状的。登革热的发病机理很复杂 由于存在四种血清型。一种血清型感染可保护个人免受未来 同一血清型的感染，但随后感染不同的血清型会增加 有症状的疾病，其中包括潜在的威胁生命的狂热者发烧和粉丝霍克 综合征。在地方性国家，儿童最有感染和疾病的风险。免疫疫苗是 对于人口保护至关重要，但儿童中实时销售疫苗的大量试验表明，年轻的年龄是 与未来感染和严重疾病有关，与其他变量无关。疫苗接种是相关的 在自然感染中，在以前出乎意料的个体中，与许多血清型交叉反应的抗体 预防多个粉丝，但短暂。长期保护很可能来自 一小部分耐用抗体，特定于一种风扇血清型。是什么决定生产 在这些类型的特异性抗体和其靶向的病毒表位中，人们对此尚不清楚。免疫学 需要结合纵向观察数据的研究以了解受保护的抗体 儿童主要天然风扇感染后的反应。 这项研究将解决年龄，抗体质量和登革热感染或疾病之间的关系。 拟议的研究将利用正在进行的纵向观察的先前收集的数据和血清 研究，尼加拉瓜Managua的小儿登革热队列研究。使用最先进的重组病毒 该提案的旨在1）比较如何） 抗体靶向的表位在患有已知登革热血清型2的年轻儿童和年龄较大的儿童中有所不同 感染和2）评估具有先前自然的年轻儿童和年龄较大的儿童的登革率可靠性的风险 登革热感染。结果将确定年轻和 年龄较大的儿童并告知有关该人群中针对登革热病毒疫苗接种的未来政策决定 还有其他拉丁美洲国家。 通过完成这些研究的目的，学员将获得一系列独特的技能 流行病学方法，病毒学和免疫学研究，包括对复杂的分析和解释 免疫学和纵向数据。病毒学，免疫学和流行病学专家指导者将支持 受训者成功完成了拟议的研究，相关培训计划和医学博士学位 北卡罗来纳大学教堂山。该F30奖学金将对申请人的发展进行严格帮助 在病毒学，免疫学和 传染病流行病学。