Field Studies of Cryptosporidiosis in Bangladesh

孟加拉国隐孢子虫病实地研究

基本信息

批准号：
10115572
负责人：
CAROL A GILCHRIST
金额：
$ 38.4万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-09-15 至 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10115572
关键词：
Acquired Immunodeficiency Syndrome Active immunity Age Age-Months Antibodies Antigenic Diversity Antigens Antiparasitic Agents Bangladesh Categories Cellular Immunity Child Childbirth Childhood Chronic diarrhea Collaborations Cryptosporidiosis Cryptosporidium DNA Resequencing Data Development Diarrhea Enteral Environment Etiology Feces Foundations Frequencies Generations Genetic Genetic Variation Genome Genomics Genotype Goals Grant Human Milk Immune response Immunity Immunoglobulin A Infant Infection Infection prevention Label Lead Life Malnutrition Measures Molecular Mothers Mucous Membrane Natural History Neurocognitive North America Oocysts Paper Parasites Parasitology Passive Immunity Peer Review Peripheral Blood Mononuclear Cell Phylogenetic Analysis Protein Array Proteins Proteome Publishing Research Research Personnel Resolution Site Slum Staphylococcus hominis Surface T-Lymphocyte Testing Trees Universities Vaccination Vaccine Design Vaccines Virginia Work acquired immunity anti-IgA base biobank biodefense cell mediated immune response clinical investigation cohort design field study genome-wide innovation innovative technologies low and middle-income countries microbial microorganism antigen neutralizing vaccine nutrition parasite genome prevent response success vaccine development waterborne

项目摘要

Project Summary Introduction: We propose to design a vaccine for Cryptosporidia by identifying antigenic targets of the parasite that are neutralized by mucosal IgA, are antigenically conserved, recognized by cell mediated immunity (CMI), and associated with protection of infants. Hypothesis: Protection from Cryptosporidia is via anti-IgA mucosal antibodies against surface-exposed antigens that provide broadly-neutralizing prevention of infection, and via cell mediated immune responses required for resolution of infection. Premise: A vaccine can be rationally designed by identifying microbial antigens that are broadly conserved and recognized by immune responses associated with protection. Significance: Cryptosporidiosis is a top 10 cause of diarrhea in the 1st year of life in low and middle-income countries. In North America it is the leading etiology of water-borne diarrhea, a biodefense category B agent, and cause of chronic diarrhea in AIDS. Investigators: The multiple PIs Drs. Petri and Gilchrist at the University of Virginia, and the foreign site lead Dr. Haque at icddr,b, have collaborated on enteric parasites for 25 years. For Cryptosporidia they have discovered in infants acquired immunity associated with a mucosal IgA response, and through genome resequencing conserved antigens. They are joined by Dr. Campo of Antigen Discovery (ADI) who brings an eminently successful track record in use of microbial proteome arrays for antigen discovery. Innovation: The identification of IgA acquired immune responses associated with protection, and application of a proteome microarray to identify targets of mucosal IgA are ground-breaking in Cryptosporidiosis Approach: There are three Specific Aims: Specific Aim 1. Assess the natural history of Cryptosporidiosis through age 5 in children in an urban slum of Dhaka, Bangladesh. Specific Aim 2: Measure the duration and magnitude of passive and active immunity associated with IgA against the parasite Cp23 antigen. Specific Aim 3: Discover antigens for a broadly neutralizing vaccine. Environment: Key to success are the complementary expertise of the team at the University of Virginia in molecular parasitology, at icddr,b in clinical investigation, and at ADI in antigen discovery. This robust collaboration has led to the substantial published and preliminary data presented in the proposal.

项目概要简介：我们建议通过识别隐孢子虫的抗原靶点来设计一种疫苗。被粘膜 IgA 中和的寄生虫，具有抗原保守性，可被细胞介导的识别免疫力（CMI），并与婴儿的保护有关。假设：针对隐孢子虫的保护是通过抗表面暴露的 IgA 粘膜抗体实现的提供广泛中和预防感染的抗原，并通过细胞介导的免疫反应解决感染所需的。前提：可以通过识别广泛保守的微生物抗原来合理设计疫苗并被与保护相关的免疫反应识别。意义：隐孢子虫病是低收入和中等收入人群一岁以内腹泻的十大原因国家。在北美，它是水源性腹泻的主要病因，是一种生物防御 B 类制剂，以及艾滋病慢性腹泻的原因。调查人员：多名 PI 博士。弗吉尼亚大学的 Petri 和 Gilchrist，国外网站负责人 icddr,b 的 Haque 博士在肠道寄生虫方面进行了 25 年的合作。对于隐孢子虫，他们有发现婴儿获得了与粘膜 IgA 反应相关的免疫力，并通过基因组对保守抗原进行重新测序。 Antigen Discovery (ADI) 的 Campo 博士也加入了他们的行列，他带来了在使用微生物蛋白质组阵列进行抗原发现方面取得了非常成功的记录。创新：IgA获得性免疫反应与保护相关的鉴定及应用蛋白质组微阵列识别粘膜 IgA 靶标在隐孢子虫病中具有开创性方法：有三个具体目标：具体目标 1. 评估 5 岁以下儿童的隐孢子虫病自然史孟加拉国达卡的一个城市贫民窟。具体目标 2：测量被动和主动免疫的持续时间和强度与针对寄生虫 Cp23 抗原的 IgA 相关。具体目标 3：发现广泛中和疫苗的抗原。环境：成功的关键是弗吉尼亚大学团队的专业知识互补分子寄生虫学，在 icddr,b 进行临床研究，在 ADI 进行抗原发现。这种坚固的合作导致提案中提供了大量已公布的初步数据。