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

• 批准号: 9285692
• 负责人: Poonum S. Korpe
• 金额: $ 18.38万
• 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/9285692
• 关键词: 1 year old; 2 year old; AIDS/HIV problem; Active immunity; Activities of Daily Living; Acute; Address; Age; Antibodies; Antigens; Bangladesh; Bangladeshi; Biological Assay; Biometry; Birth; Breast Feeding; Breastfed infant; CD4 Positive T Lymphocytes; Cause of Death; Cell Line; Cells; Cellular Immunity; Child; Clinical; Cognitive; Cognitive deficits; Communicable Diseases; Confounding Factors (Epidemiology); Cox Proportional Hazards Models; Cryptosporidiosis; Cryptosporidium; Cryptosporidium parvum; Cytometry; Data; Development; Development Plans; Diarrhea; 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 prevention; Interferons; International; Intestines; K-Series Research Career Programs; Lactoferrin; Life; Link; Literature; Longitudinal cohort study; Malnutrition; Mass Spectrum Analysis; Measures; Mediating; Mediator of activation protein; Medicine; Mentors; Mentorship; Methods; Monitor; Mothers; Natural History; Nature; Nursing infant; Oocysts; Parasites; Parasitology; Passive Immunity; Peripheral Blood Mononuclear Cell; Phenotype; Positioning Attribute; Predisposition; Prevention; Prevention strategy; Proteins; Protozoan Infections; Protozoan Vaccines; 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

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）：隐孢子虫病是全球儿童腹泻病的主要原因；但是，这种原生动物感染的疗法有限，没有可用的疫苗。在这个项目中，我建议在孟加拉国儿童中对隐孢子虫病的免疫和获得免疫力，我建议研究出生队列中隐孢子虫病的自然史 孟加拉国的儿童是了解人类对感染的免疫反应的一种手段。我们发现，该队列中有40％的儿童感染了隐孢子虫属。到1岁时，我发现抗晶状体孢子乳IgA与隐孢子虫属的保护有关。母乳喂养婴儿感染。自上次提交以来，我发现在12个月大的儿童中存在抗晶状体IgG与第二年的保护抗原有关，这表明获得了获得的免疫力。在此提案中，AIM 1将使用一种新型的体外寄生虫入侵测定法阐明母乳干扰感染的机制。 AIM 2涉及单细胞质量细胞仪（CytoF）的首次应用来描述刺激的免疫细胞的表型和功能能力，以评估鲁棒细胞介导的对隐孢子虫SPP的反应。可以预测免受复发感染的保护。该提案利用了我的导师的NIH和盖茨基金会资助的项目，利用了一项纵向队列研究。确定被动和主动免疫在保护免受隐孢子虫病中的作用将为旨在防止隐孢子虫属的免疫策略提供信息。幼儿感染。我目前正在完成奖学金的弗吉尼亚大学传染病部门对学术医学和国际健康的承诺历史悠久，并为进步的年轻调查人员提供了支持环境。拟议的职业发展计划旨在解决将进化为独立调查员地位所需的特定技能集，其中包括Petri博士和顾问的指导，这些顾问是寄生虫学和免疫学领域的专家。此外，职业发展计划概述了免疫学，生物统计学，临床研究以及免疫学方法的技术培训和专业发展活动的研究生课程。我将在Cryptosporidiosis工作的K奖第4年提交自己的R01。成功完成指导的职业发展奖将使我成为独立研究者的位置，着重于隐孢子虫病的预防策略。