Subunit Vaccine for Cryptosporidiosis
隐孢子虫病亚单位疫苗
基本信息
- 批准号:10312809
- 负责人:
- 金额:$ 20.19万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-12-07 至 2023-11-30
- 项目状态:已结题
- 来源:
- 关键词:Acquired Immunodeficiency SyndromeAdjuvantAntigensCategoriesCellsChildChronic diarrheaClinicalCollaborationsCryptosporidiosisCryptosporidiumCyclic GMPDNA ResequencingDevelopmentDiarrheaEnteralEnvironmentEnzyme-Linked Immunosorbent AssayEscherichia coliEtiologyFormulationFoundationsFoxesGenerationsGeneticGenetic VariationGenomeGoalsImmunizationImmunoglobulin AImmunoglobulin GImmunologyInfantInfantile DiarrheaInfectionInfection preventionInterferon Type IIIntestinesLeadLifeLife Cycle StagesLiposomesMeasurementMeasuresMucosal ImmunityMucous MembraneMusNorth AmericaParasitesParticle SizePathogenesisPharmacologic SubstancePositioning AttributePreventionProteinsResearch PersonnelRoleRouteSafetySporozoitesStaphylococcus hominisSubunit VaccinesTLR4 geneTLR7 geneTestingUniversitiesVaccine DesignVaccinesVirginiaacquired immunityanti-IgAbiodefensechild protectionenteric infectionglobal healthhigh riskimmunogenicityinnovationlight scatteringlow and middle-income countriesmicrobialmouse modelmucosal vaccinenovelprogramsprototyperesponsewaterborneweight maintenance
项目摘要
Project Summary
Introduction: We propose to develop a prototype subunit mucosal vaccine for cryptosporidiosis, building on
our discovery that mucosal IgA directed against Cp23 and Cp17 is associated with protection of children
from re-infection
Hypothesis: A mucosal vaccine will provide broadly neutralizing protection via mucosal IgA and IFNg.
Premise: The presence of naturally acquired immunity against cryptosporidiosis indicates that a vaccine is
feasible despite the presence of parasite genetic diversity.
Significance: Currently no vaccine exists and therapy for infants is suboptimal. Cryptosporidiosis is a top ten
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.
Investigator: Dr. William Petri at the University of Virginia pioneered the identification of cryptosporidium as
a major cause of infant diarrhea, discovered the importance in children of mucosal anti-cryptosporidium IgA
for acquired immunity and has led the application of mucosal-targeted adjuvants for subunit vaccine design.
The stage is thus set for rapid advancement of a cryptosporidiosis vaccine.
Innovation: Innovation includes the discovery that fecal IgA against the cryptosporidium Cp23 and Cp17
antigens are associated with protection from re-infection, pioneering development of mucosal adjuvants for
enteric infections, and demonstrating the genetic conservation of Cp23, CpGAPM2 and to a lesser extent
Cp17 from genome resequencing.
Approach:
Specific Aim 1. Develop a prototype mucosal vaccine. Antigens (Cp23, Cp17 and CpGAPM2) will be
expressed in E. coli, purified and mixed with our lead pharmaceutically acceptable mucosal adjuvant.
Specific Aim 2. Optimize immunogenicity and test protection of the mucosal vaccine. Mucosal IgA and
systemic IFNg will be optimized and protection tested in the mouse model of cryptosporidiosis.
Environment: The Petri lab is part of a robust program on global health and microbial
immunology/pathogenesis at the University of Virginia.
Successful Completion of this high-risk and high-payoff exploratory project will provide a foundation for
development of a mucosal vaccine for cryptosporidiosis.
项目总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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William A Petri其他文献
Environmental enteropathy and malnutrition: do we know enough to intervene?
- DOI:
10.1186/s12916-014-0187-1 - 发表时间:
2014-10-14 - 期刊:
- 影响因子:8.300
- 作者:
William A Petri;Caitlin Naylor;Rashidul Haque - 通讯作者:
Rashidul Haque
The Environmental Enteric Dysfunction Biopsy Initiative (EEDBI) Consortium: mucosal investigations of environmental enteric dysfunction
环境肠道功能障碍活检倡议(EEDBI)联盟:环境肠道功能障碍的黏膜研究
- DOI:
10.1016/j.ajcnut.2024.02.003 - 发表时间:
2024-09-01 - 期刊:
- 影响因子:6.900
- 作者:
Donna M Denno;Sheraz Ahmed;Tahmeed Ahmed;S Asad Ali;Beatrice Amadi;Paul Kelly;Sarah Lawrence;Mustafa Mahfuz;Chelsea Marie;Sean R Moore;James P Nataro;William A Petri;Peter B Sullivan;Phillip I Tarr;Kumail Ahmed;Md Ashraful Alam;Barrett H Barnes;SM Khodeza Nahar Begum;Stephen M Borowitz;Kanta Chandwe;Fayaz Umrani - 通讯作者:
Fayaz Umrani
Histopathology underlying environmental enteric dysfunction in a cohort study of undernourished children in Bangladesh, Pakistan, and Zambia compared with United States children
孟加拉国、巴基斯坦和赞比亚营养不良儿童队列研究与美国儿童相比的环境性肠功能障碍的组织病理学基础
- DOI:
10.1016/j.ajcnut.2024.02.028 - 发表时间:
2024-09-01 - 期刊:
- 影响因子:6.900
- 作者:
Paul Kelly;Kelley VanBuskirk;David Coomes;Samer Mouksassi;Gerald Smith;Zehra Jamil;Md Shabab Hossain;Sana Syed;Chelsea Marie;Phillip I Tarr;Peter B Sullivan;William A Petri;Donna M Denno;Tahmeed Ahmed;Mustafa Mahfuz;S Asad Ali;Sean R Moore;I Malick Ndao;Guillermo J Tearney;Ömer H Yilmaz;Kanekwa Zyambo - 通讯作者:
Kanekwa Zyambo
Multiplexed immunohistochemical evaluation of small bowel inflammatory and epithelial parameters in environmental enteric dysfunction
环境性肠功能障碍中小肠炎症和上皮参数的多重免疫组化评估
- DOI:
10.1016/j.ajcnut.2024.02.033 - 发表时间:
2024-09-01 - 期刊:
- 影响因子:6.900
- 作者:
Kelley VanBuskirk;Monica Mweetwa;Tad Kolterman;Shyam Raghavan;Tahmeed Ahmed;S Asad Ali;SM Khodeza Nahar Begum;Ellen Besa;Donna M Denno;Zehra Jamil;Paul Kelly;Mustafa Mahfuz;Sean R Moore;Samer Mouksassi;William A Petri;Phillip I Tarr;Peter B Sullivan;Christopher A Moskaluk;Kumail Ahmed;Sheraz Ahmed;Omer H Yilmaz - 通讯作者:
Omer H Yilmaz
Duodenal transcriptomics demonstrates signatures of tissue inflammation and immune cell infiltration in children with environmental enteric dysfunction across global centers
十二指肠转录组学显示了全球多个中心环境肠道功能障碍儿童组织炎症和免疫细胞浸润的特征
- DOI:
10.1016/j.ajcnut.2024.02.023 - 发表时间:
2024-09-01 - 期刊:
- 影响因子:6.900
- 作者:
Chelsea Marie;Subhasish Das;David Coomes;Tahmeed Ahmed;S Asad Ali;Junaid Iqbal;Paul Kelly;Mustafa Mahfuz;Sean R Moore;William A Petri;Phillip I Tarr;Lee A Denson;Kumail Ahmed;Sheraz Ahmed;Md Ashraful Alam;David Auble;SM Khodeza Nahar Begum;Ellen Besa;Mubanga Chama;Donna M Denno;Kanekwa Zyambo - 通讯作者:
Kanekwa Zyambo
William A Petri的其他文献
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{{ truncateString('William A Petri', 18)}}的其他基金
Role of Th17 in Severe and Recurrent C. difficile Infection
Th17 在严重和复发性艰难梭菌感染中的作用
- 批准号:
10223165 - 财政年份:2020
- 资助金额:
$ 20.19万 - 项目类别:
Role of Th17 in Severe and Recurrent C. difficile Infection
Th17 在严重和复发性艰难梭菌感染中的作用
- 批准号:
10653065 - 财政年份:2020
- 资助金额:
$ 20.19万 - 项目类别:
Role of Th17 in Severe and Recurrent C. difficile Infection
Th17 在严重和复发性艰难梭菌感染中的作用
- 批准号:
10443698 - 财政年份:2020
- 资助金额:
$ 20.19万 - 项目类别:
University of Virginia - icddr,b Research Unit for Women's and Children's Health Research
弗吉尼亚大学 - icddr,b 妇女和儿童健康研究单位
- 批准号:
10176548 - 财政年份:2018
- 资助金额:
$ 20.19万 - 项目类别:
NICHD Global Network for Women’s and Children’s Health Research: Research Units
NICHD 全球妇女和儿童健康研究网络:研究单位
- 批准号:
10746195 - 财政年份:2018
- 资助金额:
$ 20.19万 - 项目类别:
University of Virginia - icddr,b Research Unit for Women's and Children's Health Research
弗吉尼亚大学 - icddr,b 妇女和儿童健康研究单位
- 批准号:
9754231 - 财政年份:2018
- 资助金额:
$ 20.19万 - 项目类别:
University of Virginia - icddr,b Research Unit for Women's and Children's Health Research
弗吉尼亚大学 - icddr,b 妇女和儿童健康研究单位
- 批准号:
10413887 - 财政年份:2018
- 资助金额:
$ 20.19万 - 项目类别:
Role of Type 2 Immunity in Innate Protection from C. difficile
2 型免疫在艰难梭菌先天保护中的作用
- 批准号:
10467414 - 财政年份:2016
- 资助金额:
$ 20.19万 - 项目类别:
Role of Type 2 Immunity in Innate Protection from C. difficile
2 型免疫在艰难梭菌先天保护中的作用
- 批准号:
10561651 - 财政年份:2016
- 资助金额:
$ 20.19万 - 项目类别:
Role of IL-23 in the Immunopathogenesis of C. difficile colitis
IL-23 在艰难梭菌结肠炎免疫发病机制中的作用
- 批准号:
9057951 - 财政年份:2015
- 资助金额:
$ 20.19万 - 项目类别:
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