Deconvolution and reconstruction of immune histories to enhance infectious disease prevention and vaccination strategies and optimize surveillance efforts

免疫历史的反卷积和重建，以加强传染病预防和疫苗接种策略并优化监测工作

• 批准号: 10260462
• 负责人: Albert Hofman
• 金额: $ 39.88万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-16 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10260462
• 关键词: Age; Antibodies; Antibody Repertoire; Appointment; Bacteria; Biology; Birth; Blood; Blood donor; Clinical; Clinical Pathology; Collaborations; Communicable Diseases; Computing Methodologies; Coupled; Culicidae; Data; Data Analyses; Dengue; Detection; Development; Discipline; Disease Surveillance; Doctor of Philosophy; Early Diagnosis; Educational process of instructing; Elderly; Epidemic; Epidemiology; Epitopes; Exposure to; Faculty; Frequencies; Funding; Future; Gender; Geography; Goals; Growth; Health; Hospitals; Human; Immune; Immunologics; Immunology; Improve Access; Individual; Infection; Interdisciplinary Study; Investigation; Journals; Laboratories; Laboratory Technicians; Leadership; Link; Longevity; Longitudinal cohort; Maternal antibody; Mathematics; Measles; Measurement; Measures; Medical; Mentors; Methods; Molecular Biology; Molecular Computations; Nicaragua; Output; Parasites; Pathology; Phage Display; Physician Executives; Population; Population Surveillance; Positioning Attribute; Postdoctoral Fellow; Prevention Measures; Prevention strategy; Property; Public Health; Public Health Schools; Publications; Recording of previous events; Reporting; Research; Research Personnel; Resources; Running; Saliva; Sampling; Series; Serology; Specimen; Spottings; Statistical Models; Structure; Students; System; Technology; Time; Training; Travel; Vaccination; Vaccines; Vascular blood supply; Wages; Water; Woman; Work; ZIKA; base; clinically relevant; co-infection; computerized tools; cost; emerging pathogen; environmental change; epidemiological model; experience; graduate student; human pathogen; improved; influenza virus vaccine; interdisciplinary approach; life history; mathematical model; medical schools; member; mortality; multidisciplinary; novel; pathogen; pathogen exposure; professor; programs; reconstruction; recruit; serosurveillance; skills; success; tenure track; tool; vaccination strategy; vector mosquito; virtual

PROJECT SUMMARY Infectious diseases remain among the greatest threats to human health. Novel epidemics occur with increasing frequency as ease of travel facilitates spread, and environmental changes alter underlying dynamics in unpredictable ways. At the same time, vaccines are increasingly controlling many major human pathogens. Yet, the potential of these advances can only be fully realized with a means to accurately measure and quantify the landscape of infectious diseases across many pathogens and scales, from the individual to the global population, and encompassing interactions and potential unintended consequences across related or unrelated pathogens. The overall objectives are to bridge novel developments in molecular biology and computational tools to fundamentally improve infectious disease surveillance and research. Aim 1 will build on a previously reported phage display system, and optimize it for infectious disease surveillance. PADERNS (Phage display for Antibody repertoire Detection and profiling via pathogen Epitope RecognitioN for infectious disease and public health Surveillance) will: enable serological surveillance for exposures to all human pathogens, including bacteria, parasites and mosquitos vectors, simultaneously, from accessible samples, i.e. saliva and dried blood spots; will discriminate exposures from closely related pathogens (i.e. Zika and Dengue) and estimate time since infection or vaccination. Importantly, it will be optimized for use in low resource settings and at a fraction of the cost of current technologies. Aim 2 will improve epidemic detection with development of Epi-TRACER (Epitope based TRacking of Anonymous samples via Comprehensive Epitope Recogntion). Epi-TRACER will use PADERNS repertoires from (1) to extract and construct epidemiologically powerful ‘virtual longitudinal cohorts’ from cross-sectional sample sets that contain ‘hidden’ serial samples (i.e. 80% of the US blood supply comes from repeat donors). Because Epi-TRACER runs on PADERNS data, it will simultaneously enable reconstruction of past, and early detection of current epidemics. Aim 3 will elucidate the life-histories of pathogen exposures across ages (pre-birth to elderly), time, genders and geographies to: quantify in unprecedented detail pathogen attack rates, heterologous effects of vaccines on off-target pathogens, and measure the longevity and waning of antibodies, including maternally derived antibodies, to improving vaccination and control strategies. These aims will be accomplished through a multi-disciplinary approach involving molecular biology and phage-display systems, robust longitudinal sample curation through collaborations, and, crucially, careful development of mathematical and statistical models to link the biology to individual and population level inference. Once complete, the tools, methods and data will be available to public health agencies and infectious disease researchers, opening the way to a step change in detection or control of existing and novel pathogens.

项目概要 传染病仍然是对人类健康的最大威胁之一。 频率，因为旅行的便捷性促进了传播，而环境变化改变了潜在的动态 与此同时，疫苗正在越来越多地控制许多主要的人类病原体。 只有通过准确测量和量化的手段才能充分实现这些进步的潜力 从个人到全球人口的多种病原体和规模的传染病景观， 并涵盖相关或无关病原体之间的相互作用和潜在的意外后果。 总体目标是将分子生物学和计算工具的新颖发展与 目标 1 将建立在先前报告的基础上，从根本上改善传染病监测和研究。 噬菌体展示系统，并对其进行优化以用于传染病监测。 通过病原体表位识别进行检测和分析，用于传染病和公共卫生 监测）将：对接触所有人类病原体（包括细菌）的情况进行血清学监测， 同时从可获取的样本（即唾液和干血斑）中检测寄生虫和蚊子媒介； 将区分密切相关的病原体（即寨卡病毒和登革热）的暴露并估计此后的时间 重要的是，它将针对在资源匮乏的环境中使用进行优化，并且只需花费一小部分。 目标 2 将通过 Epi-TRACER（表位）的开发来改善流行病检测。 将使用基于 Epi-TRACER 的匿名样本跟踪。 PADERNS 的全部技能来自 (1)，用于提取和构建流行病学上强大的“虚拟纵向队列” 来自包含“隐藏”系列样本的横截面样本集（即美国 80% 的血液供应来自 由于 Epi-TRACER 在 PADERNS 数据上运行，因此它将同时启用重建。 目标 3 将阐明病原体暴露的生活史。 跨年龄（从出生前到老年人）、时间、性别和地域：以前所未有的详细程度量化病原体 攻击率、疫苗对脱靶病原体的异源效应，并衡量病原体的寿命和衰退 抗体，包括母源抗体，以改善疫苗接种和控制策略。 这些目标将通过涉及分子生物学和 噬菌体展示系统，通过合作进行强大的纵向样本管理，以及最重要的是，仔细 开发数学和统计模型，将生物学与个体和群体水平联系起来 一旦完成，工具、方法和数据将可供公共卫生机构和传染病机构使用。 疾病研究人员，为检测或控制现有和新型病原体的一步改变开辟了道路。

项目成果

Assessing the Effects of Measles Virus Infections on Childhood Infectious Disease Mortality in Brazil.

评估麻疹病毒感染对巴西儿童传染病死亡率的影响。

• DOI: 10.1093/infdis/jiac233
• 发表时间: 2022
• 期刊: The Journal of infectious diseases
• 作者: Xia,Siyang;Gullickson,CricketC;Metcalf,CJessicaE;Grenfell,BryanT;Mina,MichaelJ
• 通讯作者: Mina,MichaelJ

Clarifying the evidence on SARS-CoV-2 antigen rapid tests in public health responses to COVID-19.

• DOI: 10.1016/s0140-6736(21)00425-6
• 发表时间: 2021-04-17
• 期刊: Lancet (London, England)
• 作者: Mina MJ;Peto TE;García-Fiñana M;Semple MG;Buchan IE
• 通讯作者: Buchan IE

Comprehensive Profiling of Zika Virus Risk with Natural and Artificial Mitigating Strategies, United States.

通过自然和人工缓解策略全面分析寨卡病毒风险，美国。

• DOI: 10.3201/eid2604.181739
• 发表时间: 2020
• 期刊: Emerging infectious diseases
• 影响因子: 11.8
• 作者: Mina,MichaelJ;Guterman,LBeryl;Allen,KristenE;Omer,SaadB
• 通讯作者: Omer,SaadB

Development of at-home sample collection logistics for large-scale seroprevalence studies.

• DOI: 10.1371/journal.pone.0258516
• 发表时间: 2021
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Aatresh AV;Cummings K;Gerstein H;Knight CS;Limberopolous A;Stasi MA;Bedugnis A;Somberg KA;França CT;Mina MJ
• 通讯作者: Mina MJ

Measles vaccine immune escape: Should we be concerned?

麻疹疫苗免疫逃逸：我们应该担心吗？

• DOI: 10.1007/s10654-019-00574-7
• 发表时间: 2019
• 期刊: European journal of epidemiology
• 影响因子: 13.6
• 作者: Yang,Luojun;Grenfell,BryanT;Mina,MichaelJ
• 通讯作者: Mina,MichaelJ