Passive and Acquired Immunity to Cryptosporidiosis in Bangladeshi Children

孟加拉国儿童对隐孢子虫病的被动和获得性免疫力

基本信息

批准号：
8874886
负责人：
Poonum S. Korpe
金额：
$ 16.81万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-06-19 至 2019-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8874886
关键词：
2 year old AIDS/HIV problem Accounting Active immunity Activities of Daily Living Acute Address Age Age-Years Antibodies Antigens Bangladesh Biological Assay Biometry Birth Breast Feeding CD4 Positive T Lymphocytes Cause of Death Cell Line Cells Cellular Immunity Child Clinical Cognitive Cognitive deficits Cohort Studies Communicable Diseases Confounding Factors (Epidemiology)Cox Proportional Hazards Models Cryptosporidiosis Cryptosporidium Cryptosporidium parvum Cytometry Data Development Development Plans Diarrhea Discipline of Nursing Disease Epidemiology Epithelial Cells Evolution Fellowship Foundations Funding Future Glycoconjugates Goals Growth Harvest Health Human Human Milk Immune Immune response Immunity Immunization Immunoglobulin A Immunoglobulin G Immunologics Immunology In Vitro Incidence Individual Infant Infection Infection Control Infection prevention Interferons International Intestines K-Series Research Career Programs Lactoferrin Left Life Link Literature Malnutrition Mass Spectrum Analysis Measures Mediating Mediator of activation protein Medicine Mentors Mentorship Methods Monitor Mothers Natural History Nature Oocysts Parasites Parasitology Passive Immunity Peripheral Blood Mononuclear Cell Phenotype Positioning Attribute Predisposition Prevention Proteins Protozoan Infections Recording of previous events Recurrence Research Personnel Risk Role Rotavirus Sampling Serological Serum Socioeconomic Status Sporozoites T-Lymphocyte Testing Training United States National Institutes of Health Universities Vaccines Virginia Vulnerable Populations Work acquired immunity age group base career development cell mediated immune response clinical investigation cohort collaborative environment defined contribution design effective therapy excystation gastrointestinal high throughput screening in vitro testing in vivo indexing nitazoxanide novel novel therapeutics parasite invasion prevent public health relevance response skills

项目摘要

DESCRIPTION (provided by applicant): Cryptosporidiosis is a leading cause of diarrheal illness in children worldwide; however there are limited therapies and no available vaccine for this protozoal infection. In this project, Passive and Acquired Immunity to Cryptosporidiosis in Bangladeshi Children, I propose to study the natural history of cryptosporidiosis in a birth cohort of children in Bangladesh as a means to understand human immune responses to the infection. We have found that 40% of children in this cohort are infected with Cryptosporidium spp. by age one, and I have discovered that anti-cryptosporidium breast milk IgA is associated with protection from Cryptosporidium spp. infection in breastfeeding infants. Since the last submission, I have found that the presence of anti-cryptosporidium IgG in 12-month old children is associated with protection from infection in year two of life, suggesting the development of acquired immunity. In this proposal, Aim 1 will elucidate the mechanism by which breast milk may interfere with infection, using a novel in vitro parasite invasion assay. Aim 2 involves the first application of single-cell mass cytometry (CyTOF) to describe the phenotype and functional capacity of stimulated immune cells to evaluate whether a robust cell-mediated response to Cryptosporidium spp. can predict protection from recurrent infection. This proposal leverages a longitudinal cohort study already in place for my mentor's NIH and Gates Foundation funded projects. Determining the role of passive and active immunity in protection from cryptosporidiosis will inform immunization strategies aimed to prevent Cryptosporidium spp. infection in young children. The Division of Infectious Diseases at the University of Virginia, where I am currently completing a fellowship, has a strong history of commitment to academic medicine and international health, and provides a supportive environment for advancement of young investigators. The proposed career development plan is designed to address specific skill sets that will be required for evolution to independent investigator status, and includes mentorship by Dr. Petri and advisors who are experts in the fields of parasitology and immunology. Additionally, the career development plan outlines graduate level courses in immunology, biostatistics, clinical investigation, as well as technical training in immunologic methods, and professional development activities. I will submit my own R01 during year 4 of the K award on the cryptosporidiosis work. Successful completion of the Mentored Career Development Award will leave me well-positioned as an independent investigator with a focus on preventative strategies to cryptosporidiosis.

描述（由申请人提供）：隐孢子虫病是全世界儿童腹泻病的主要原因；然而，针对这种原虫感染的治疗方法有限，也没有可用的疫苗。在这个项目“孟加拉国儿童对隐孢子虫病的被动和获得性免疫”中，我建议研究出生队列中隐孢子虫病的自然史孟加拉国儿童的研究作为了解人类对感染的免疫反应的一种手段。我们发现该队列中 40% 的儿童感染了隐孢子虫属。到了一岁时，我发现抗隐孢子虫母乳 IgA 与对隐孢子虫的保护有关。母乳喂养的婴儿感染。自上次提交以来，我发现 12 个月大的儿童体内存在抗隐孢子虫 IgG，与出生后第二年免受感染的保护有关，这表明获得性免疫力的发展。在该提案中，目标 1 将使用一种新型体外寄生虫入侵测定来阐明母乳可能干扰感染的机制。目标 2 涉及首次应用单细胞质谱流式细胞仪 (CyTOF) 来描述受刺激免疫细胞的表型和功能能力，以评估是否对隐孢子虫属有强大的细胞介导反应。可以预测对复发感染的保护。该提案利用了我导师的美国国立卫生研究院和盖茨基金会资助的项目中已有的纵向队列研究。确定被动和主动免疫在预防隐孢子虫病中的作用将为旨在预防隐孢子虫病的免疫策略提供信息。幼儿感染。我目前正在弗吉尼亚大学传染病系完成研究金，该系有着致力于学术医学和国际卫生的悠久历史，并为年轻研究人员的进步提供了支持性环境。拟议的职业发展计划旨在解决发展为独立研究者身份所需的特定技能，包括 Petri 博士和寄生虫学和免疫学领域专家顾问的指导。此外，职业发展计划还概述了免疫学、生物统计学、临床研究的研究生水平课程，以及免疫学方法的技术培训和专业发展活动。我将在隐孢子虫病 K 奖的第 4 年期间提交我自己的 R01。成功完成指导职业发展奖将使我成为一名独立调查员，专注于隐孢子虫病的预防策略。