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: 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
• 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

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。在这个项目中，孟加拉国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史