Field Studies of Cryptosporidiosis in Bangladesh

孟加拉国隐孢子虫病实地研究

• 批准号: 10585918
• 负责人: CAROL A GILCHRIST
• 金额: $ 38.25万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-15 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10585918
• 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; Surface; T-Lymphocyte; Testing; Trees; Universities; Vaccination; Vaccine Design; Vaccines; Virginia; Work; acquired immunity; anti-IgA; 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; rational design; response; success; vaccine development; waterborne

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.

项目摘要 简介：我们建议通过识别抗原靶标的隐孢子虫设计疫苗 被粘膜IgA中和的寄生虫是抗原保守的，通过细胞介导的识别 免疫（CMI），与婴儿的保护有关。 假设：免受隐孢子虫的保护是通过抗IGA粘膜抗体抗表面暴露的 提供广泛不中和预防感染的抗原，并通过细胞介导的免疫反应 消除感染所必需的。 前提：可以通过识别广泛保守的微生物抗原来理性设计疫苗 并通过与保护相关的免疫反应认可。 意义：隐孢子虫病是低收入和中等收入的第一年腹泻的十大原因 国家。在北美，它是水传播腹泻的领先病因，生物形式B类代理 和艾滋病慢性腹泻的原因。 调查人员：多个PIS DRS。弗吉尼亚大学的彼得里和吉尔克里斯特和外国现场领导 ICDDR的Haque博士在肠道寄生虫上合作了25年。对于cryptosporidia，他们有 在婴儿中发现的获得与粘膜IgA反应相关的免疫力，并通过基因组发现 重新定制保守的抗原。抗原发现（ADI）的Campo博士加入了他们，他带来了 在使用微生物蛋白质组阵列进行抗原发现时，取得了成功的记录。 创新：IGA获得的识别与保护和申请相关的免疫反应 识别粘膜IgA靶标的蛋白质组微阵列在隐孢子虫病中开创性 方法：有三个具体目标： 特定目的1。通过5岁儿童在儿童中评估隐孢子虫病的自然历史 孟加拉国达卡的城市贫民窟。 特定目标2：测量被动和主动免疫的持续时间和幅度 与IgA相关的针对寄生虫CP23抗原。 特定目的3：发现抗原的抗原，用于广泛中和疫苗。 环境：成功的关键是弗吉尼亚大学的团队的补充专业知识 分子寄生虫学，在ICDDR，B，临床研究和ADI抗原发现。这个坚固的 合作导致了该提案中提供的大量发布和初步数据。

项目成果

Brain morphometry and diminished physical growth in Bangladeshi children growing up in extreme poverty: A longitudinal study.

• DOI: 10.1016/j.dcn.2021.101029
• 发表时间: 2021-12
• 期刊: Developmental cognitive neuroscience
• 影响因子: 4.7
• 作者: Turesky TK;Shama T;Kakon SH;Haque R;Islam N;Someshwar A;Gagoski B;Petri WA Jr;Nelson CA;Gaab N
• 通讯作者: Gaab N

Evaluation of a Rapid Lateral Flow Point-of-Care Test for Detection of Cryptosporidium.

• DOI: 10.4269/ajtmh.16-0132
• 发表时间: 2016-10-05
• 期刊: The American journal of tropical medicine and hygiene
• 作者: Fleece ME;Heptinstall J;Khan SS;Kabir M;Herbein J;Haque R;Petri WA
• 通讯作者: Petri WA

Case-Control Study of Cryptosporidium Transmission in Bangladeshi Households.

• DOI: 10.1093/cid/ciy593
• 发表时间: 2019-03-19
• 期刊: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
• 作者: Korpe PS;Gilchrist C;Burkey C;Taniuchi M;Ahmed E;Madan V;Castillo R;Ahmed S;Arju T;Alam M;Kabir M;Ahmed T;Petri WA;Haque R;Faruque ASG;Duggal P
• 通讯作者: Duggal P

Global, regional, and national under-5 mortality, adult mortality, age-specific mortality, and life expectancy, 1970-2016: a systematic analysis for the Global Burden of Disease Study 2016.

• DOI: 10.1016/s0140-6736(17)31833-0
• 发表时间: 2017-09-16
• 期刊: Lancet (London, England)
• 作者: GBD 2016 Mortality Collaborators

A review of the global burden, novel diagnostics, therapeutics, and vaccine targets for cryptosporidium.

• DOI: 10.1016/s1473-3099(14)70772-8
• 发表时间: 2015-01
• 期刊: LANCET INFECTIOUS DISEASES
• 影响因子: 56.3
• 作者: Checkley, William;White, A. Clinton, Jr.;Jaganath, Devon;Arrowood, Michael J.;Chalmers, Rachel M.;Chen, Xian-Ming;Fayer, Ronald;Griffiths, Jeffrey K.;Guerrant, Richard L.;Hedstrom, Lizbeth;Huston, Christopher D.;Kotloff, Karen L.;Kang, Gagandeep;Mead, Jan R.;Miller, Mark;Petri, William A., Jr.;Priest, Jeffrey W.;Roos, David S.;Striepen, Boris;Thompson, R. C. Andrew;Ward, Honorine D.;Van Voorhis, Wesley A.;Xiao, Lihua;Zhu, Guan;Houpt, Eric R.
• 通讯作者: Houpt, Eric R.