Immune Response to Cryptosporidiosis in a Birth Cohorot of Children of South Indi

南印度儿童出生队列对隐孢子虫病的免疫反应

• 批准号: 7687425
• 负责人: Honorine D Ward
• 金额: $ 56.54万
• 依托单位: TUFTS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-16 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7687425
• 关键词: 3 year old; Acquired Immunodeficiency Syndrome; Address; Adult; Antibodies; Antigens; Area; Arts; Birth; Boston; CD7 gene; Cells; Child; Childhood; Cohort Studies; Communities; Country; Cryptosporidiosis; Cryptosporidium; Data; Developed Countries; Developing Countries; Diarrhea; Disease; Enteral; Funding; Future; Genes; Genetic Polymorphism; Goals; Growth; Human; Immune; Immune response; Immunity; Immunocompetent; Immunocompromised Host; India; Infant Mortality; Infection; Infection Control; Intervention; Knowledge; Lead; Measures; Mediating; Medical center; Methodology; Molecular; New England; Nutritional status; Parasites; Patients; Peptides; Pilot Projects; Play; Prospective Studies; Proteins; Recombinants; Research; Role; Sampling; Severities; Site; Slum; Sporozoites; Symptoms; Vaccines; acquired immunity; base; cognitive function; cohort; data modeling; design; disorder control; early childhood; high risk; innovation; medical schools; prevent; public health relevance; repository; response; therapy development; transmission process; vaccine development

DESCRIPTION (provided by applicant): The overall goal of this collaborative study between Tufts-New England Medical Center, Boston MA and Christian Medical College, Vellore, India is to investigate the immune response to natural Cryptosporidium spp. infections in children in southern India. Cryptosporidiosis is an important cause of diarrhea in children in developing countries and is the commonest cause of parasitic diarrhea at the study site. The correlates of protective immunity to cryptosporidiosis in humans are poorly understood and there is little information on whether immunity to this parasite is subtype-specific. Knowledge of naturally acquired immunity to specific Cryptosporidium spp. antigens is essential to design strategies to prevent or control disease caused by this parasite. The first specific aim is to investigate the role of immune responses to recombinant (r) antigens rgp15, rp27, rgp900 as well as sporozoite lysate in determining the course of Cryptosporidium infections in children from birth to 3 years of age. We will determine whether immune responses to these antigens are associated with control of infection in primary cryptosporidiosis. We will then determine whether immune responses to these antigens resulting from the primary infection are associated with protection from subsequent infection. The second specific aim is to investigate subtype-specific immune responses to the polymorphic gp40 antigen. We will determine whether repeated episodes of cryptosporidiosis involve the same or different species and subtypes of Cryptosporidium. We will then determine whether immune responses to subtype-specific gp40 are associated with control of the primary infection and whether immune responses to rgp40 1a in children infected with subtype 1a in the primary infection are associated with protection from subsequent homotypic or heterotypic infection. This study is innovative because it will be the first prospective study of subtype- specific immune response in cryptosporidiosis in humans. It is significant because there are no data from longitudinal birth cohort studies that address correlates of protective immunity together with subtype-specific immune responses to this disease in humans. These data will provide the basis for the logical development of interventions, such as appropriate vaccines. PUBLIC HEALTH RELEVANCE: The goal of this collaborative study between Tufts-New England Medical Center, Boston MA and Christian Medical College, Vellore, is to investigate immunity to Cryptosporidium in children in southern India. This parasite is the commonest cause of parasitic diarrhea in this area and there is no vaccine available. Results obtained from this study will be useful for development of vaccines against this parasite.

描述（由申请方提供）：Tufts-New England Medical Center，Boston MA和Christian Medical College，韦洛雷，India之间的这项合作研究的总体目标是研究对天然隐孢子虫属的免疫应答。在印度南部的儿童感染。隐孢子虫病是发展中国家儿童腹泻的重要原因，也是研究中心寄生虫性腹泻的最常见原因。人类对隐孢子虫病的保护性免疫的相关性知之甚少，关于对这种寄生虫的免疫是否具有亚型特异性的信息也很少。对特定隐孢子虫属的自然获得性免疫的知识。抗原对于设计预防或控制由这种寄生虫引起的疾病的策略至关重要。第一个具体的目的是研究重组（r）抗原rgp 15，rp 27，rgp 900以及子孢子裂解物的免疫应答在确定从出生到3岁的儿童隐孢子虫感染的过程中的作用。我们将确定对这些抗原的免疫反应是否与原发性隐孢子虫病的感染控制有关。然后，我们将确定由初次感染引起的对这些抗原的免疫应答是否与对后续感染的保护有关。第二个具体目标是研究对多态性gp 40抗原的亚型特异性免疫应答。我们将确定是否重复发作的隐孢子虫病涉及相同或不同的物种和亚型的隐孢子虫。然后，我们将确定是否亚型特异性gp 40的免疫反应与控制原发感染和rgp 40 1a的免疫反应是否与保护随后的同型或异型感染在原发感染中感染1a亚型的儿童。这项研究具有创新性，因为它将是人类隐孢子虫病亚型特异性免疫反应的首个前瞻性研究。这是重要的，因为没有纵向出生队列研究的数据，解决相关的保护性免疫力与亚型特异性免疫反应，这种疾病在人类。这些数据将为合理制定干预措施（如适当的疫苗）提供基础。公共卫生关系：这项由马萨诸塞州波士顿塔夫茨-新英格兰医学中心和韦洛雷基督教医学院合作进行的研究的目的是调查印度南部儿童对隐孢子虫的免疫力。这种寄生虫是该地区寄生虫性腹泻的最常见原因，目前尚无疫苗。从这项研究中获得的结果将是有用的，针对这种寄生虫的疫苗的发展。