Translational Research to Prevent and Control Global Infectious Diseases (Translational Global Infectious Diseases Research Center, TGIR).

预防和控制全球传染病的转化研究（转化全球传染病研究中心，TGIR）。

• 批准号: 10853787
• 负责人: Beth Diane Kirkpatrick
• 金额: $ 96.23万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-15 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10853787
• 关键词: Achievement; Adult; Antibody Response; Attenuated; Attenuated Vaccines; Bangladesh; Biometry; Biostatistical Methods; Centers of Research Excellence; Cessation of life; Characteristics; Child; Childhood; Communicable Diseases; Communities; Complex; Cryopreservation; Data; Data Science; Development; Diarrhea; Dose; Enteral; Future; Geographic Locations; Goals; Gut Mucosa; Hand; Human; Human poliovirus; Immune response; Immunity; Immunophenotyping; Infant; Infection; Infectious Diseases Research; Intestines; Investigation; Knowledge; Life; Lipopolysaccharides; Machine Learning; Measures; Metabolic; Metagenomics; Methodology; Methods; Microbiology; Modeling; Molecular Epidemiology; Mucosal Immune Responses; Mucosal Immunity; Oral; Outcome; Performance; Peripheral Blood Mononuclear Cell; Physiological Processes; Plasma; Poliomyelitis; Poliovirus Vaccines; Predisposition; Public Health; Research; Research Personnel; Resource-limited setting; Resources; Role; Rotavirus; Rotavirus Vaccines; Sampling; Surface; System; Target Populations; Taxonomy; Technology; Testing; Time; Transcend; Translational Research; Universities; Vaccinated; Vaccination; Vaccine Design; Vaccines; Vermont; Virus; Virus Shedding; Work; burden of illness; cell mediated immune response; cohort; college; computerized tools; deep learning; diarrheal disease; disorder prevention; enteric pathogen; fecal microbiome; fecal microbiota; gut microbiome; gut microbiota; health goals; high dimensionality; host microbiome; immune activation; immunoregulation; improved; innovation; longitudinal dataset; low and middle-income countries; metagenomic sequencing; microbial; microbial community; microbiome; microbiome analysis; microbiota; network models; novel; novel strategies; oral vaccine; permissiveness; prevent; public health intervention; response; response biomarker; stool sample; success; vaccination strategy; vaccine effectiveness; vaccine immunogenicity; vaccine response; vaccine trial; young adult

ABSTRACT The human gut microbiota is a modifiable effector of many physiological processes including immune response. Live attenuated oral vaccines stimulate immunity at the gut mucosal surface, a microenvironment teeming with diverse microbial taxa living in complex interacting and dynamically evolving communities. Evidence suggests that the gut microbiome is responsible for some of the differences observed in oral vaccine response that challenge disease prevention efforts in resource-limited settings, but many knowledge gaps remain. Understanding the effects of the gut microbiome on oral vaccine response is key to overcoming two of the most critical problems in pediatric global public health: polio eradication, which, if successful, would be among the greatest global public health achievements; and rotavirus, a vaccine-preventable cause of diarrhea still responsible for well over 100,000 pediatric deaths per year. We have assembled an interdisciplinary team of current and former COBRE Project Leaders from University of Vermont’s Translational Global Infectious Diseases Research (TIGR) Center and Dartmouth College’s Center for Molecular Epidemiology. This team will take on a new project aimed at evaluating the role of the gut microbiome in oral vaccine take and response that builds upon existing research themes and leverages the resources of both centers. Our new collaborative project will create rich metagenomic data sets of longitudinal stool sampling from existing vaccine trials with multiple vaccine response biomarkers already measured. To these data, we will apply established biostatistical approaches and develop and apply a novel machine learning approach to identify features of the microbiome related to development of protective and mucosal immune responses. This project will result in data that can inform subsequent long-term investigations of major ongoing questions in oral vaccine response as a function of the complex systems at the microbiome-host interface.

抽象的 人肠道菌群是许多物理过程（包括免疫响应）的可修改效应子。 现场减弱口服疫苗在肠道粘膜表面刺激免疫组织化学，一种微环境与 生活在复杂的互动和动态发展的社区中的各种微生物类群。有证据表明 肠道微生物组负责口服疫苗反应中观察到的一些差异 在资源有限的环境中挑战预防疾病的努力，但仍然存在许多知识差距。 了解肠道微生物组对口服疫苗反应的影响是克服最大两个的关键 小儿全球公共卫生中的关键问题：根除脊髓灰质炎，如果成功的话，将是 全球最大的公共卫生成就；和轮状病毒，腹泻的可预防疫苗的原因仍然 每年负责超过100,000个小儿死亡。我们组建了一个跨学科团队 佛蒙特大学翻译全球感染力的现任和前毛培项目领导者 疾病研究中心和达特茅斯学院的分子流行病学中心。这个团队会 采取一个旨在评估肠道微生物组在口服疫苗服用和反应中的作用的新项目 建立在现有研究主题的基础上，并利用两个中心的资源。我们的新协作项目 将创建来自现有疫苗试验的纵向粪便采样的丰富的宏基因组数据集 疫苗反应生物标志物已经测量。对于这些数据，我们将应用已建立的生物统计学 方法并开发并应用新颖的机器学习方法来识别微生物组的特征 与受保护和粘膜免疫反应的发展有关。该项目将导致数据可以 告知随后对口服疫苗反应中正在进行的正在进行的问题的长期调查 微生物组主机接口处的复杂系统。

项目成果

Macroscopic patterns of interacting contagions are indistinguishable from social reinforcement.

• DOI: 10.1038/s41567-020-0791-2
• 发表时间: 2020-04
• 期刊: Nature physics
• 影响因子: 19.6
• 作者: Hébert-Dufresne L;Scarpino SV;Young JG
• 通讯作者: Young JG

Social Confinement and Mesoscopic Localization of Epidemics on Networks.

• DOI: 10.1103/physrevlett.126.098301
• 发表时间: 2021-03-05
• 期刊: Physical review letters
• 影响因子: 8.6
• 作者: St-Onge G;Thibeault V;Allard A;Dubé LJ;Hébert-Dufresne L
• 通讯作者: Hébert-Dufresne L

Maternal Secretor Status Affects Oral Rotavirus Vaccine Response in Breastfed Infants in Bangladesh.

• DOI: 10.1093/infdis/jiaa101
• 发表时间: 2021-10-13
• 期刊: The Journal of infectious diseases
• 作者: Williams FB;Kader A;Colgate ER;Dickson DM;Carmolli M;Uddin MI;Sharmin S;Islam S;Bhuiyan TR;Alam M;Nayak U;Mychaleckyj JC;Petri WA;Haque R;Qadri F;Kirkpatrick BD;Lee B
• 通讯作者: Lee B

Pediatric acute gastroenteritis associated with adenovirus 40/41 in low-income and middle-income countries.

• DOI: 10.1097/qco.0000000000000663
• 发表时间: 2020-10
• 期刊: Current opinion in infectious diseases
• 影响因子: 3.9
• 作者: Lee B;Damon CF;Platts-Mills JA
• 通讯作者: Platts-Mills JA

Spatial epidemiology and adaptive targeted sampling to manage the Chagas disease vector Triatoma dimidiata.

• DOI: 10.1371/journal.pntd.0010436
• 发表时间: 2022-06
• 期刊: PLOS NEGLECTED TROPICAL DISEASES
• 影响因子: 3.8
• 作者: Case, B. K. M.;Young, Jean-Gabriel;Penados, Daniel;Monroy, Carlota;Hebert-Dufresne, Laurent;Stevens, Lori
• 通讯作者: Stevens, Lori