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

• 批准号: 8962266
• 负责人: Poonum S. Korpe
• 金额: $ 14.4万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 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/8962266
• 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; Clinical Trials; 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; Environment; 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; Serology; 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; cohort; 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

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(申请人提供)：隐孢子虫病是全世界儿童腹泻疾病的主要原因；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，孟加拉儿童对隐孢子虫病的被动和获得性免疫，我建议研究出生队列中隐孢子虫病的自然历史 作为了解人类对感染的免疫反应的一种手段。我们发现，这一队列中40%的儿童感染了隐孢子虫。在一岁的时候，我发现抗隐孢子虫母乳免疫球蛋白A与保护隐孢子虫有关。母乳喂养婴儿的感染。自从上一次提交以来，我发现12个月大的儿童中存在抗隐孢子虫免疫球蛋白与第二年免受感染有关，这表明获得性免疫的发展。在这项提案中，Aim 1将使用一种新的体外寄生虫入侵试验来阐明母乳可能干扰感染的机制。目的2首次应用单细胞质量细胞术(CyTOF)描述被刺激的免疫细胞的表型和功能能力，以评估对隐孢子虫是否有强大的细胞介导反应。可以预测对复发感染的保护。这项建议利用了我导师的NIH和盖茨基金会资助的项目已经进行的纵向队列研究。确定被动免疫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的免疫战略提供依据。幼儿感染。我目前正在弗吉尼亚大学完成一项研究，弗吉尼亚大学传染病学部在致力于学术医学和国际卫生方面有着深厚的历史，并为年轻研究人员的进步提供了一个支持性的环境。拟议的职业发展计划旨在解决发展为独立调查员所需的特定技能，并包括由皮里博士和寄生虫学和免疫学领域的专家顾问提供的指导。此外，职业发展计划概述了免疫学、生物统计学、临床调查以及免疫学方法的技术培训和专业发展活动方面的研究生水平课程。我将在K奖的第四年提交我自己的R01关于隐孢子虫病的工作。成功完成导师职业发展奖将使我作为一名独立研究员处于有利地位，专注于预防隐孢子虫病的策略。