HIGH-THROUGHPUT EPITOPE DISCOVERY: USE OF NEXT-GENERATION PEPTIDE CHIPS FOR FAST IDENTIFICATION AND FINE MAPPING OF DIAGNOSTIC AND PROGNOSTIC MARKERS FOR CHAGAS DISEASE

高通量表位发现：使用下一代肽芯片快速识别南美锥虫病的诊断和预后标志物并对其进行精细定位

• 批准号: 9886074
• 负责人: Fernan Gonzalo Aguero
• 金额: $ 10.61万
• 依托单位: INSTITUTE/RESEARCH/BIOTECHNOLOGY FDN
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-15 至 2022-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9886074
• 关键词: Acute; Adult; Americas; Amino Acids; Antibodies; Antibody Diversity; Antibody Response; Antigens; Area; B-Lymphocyte Epitopes; B-Lymphocytes; Benznidazole; Binding; Binding Proteins; Biological Assay; Biological Markers; Blood Banks; Blood Screening; Blood Transfusion; Certification; Chagas Disease; Child; Chronic; Clinical; Clinical Trials; Collection; Communities; Comparative Study; Complement; Data; Data Set; Detection; Development; Diagnosis; Diagnostic; Diagnostic tests; Differential Diagnosis; Disease; Disease Surveillance; Enzyme-Linked Immunosorbent Assay; Epitopes; Failure; Future; Genetic; Goals; Human; Immune response; In Situ; Individual; Infection; Insect Bites; Latin America; Lead; Learning; Link; Maintenance; Maps; Methods; Monitor; Noise; Organ Transplantation; Outcome; Parasites; Patients; Peptides; Pharmaceutical Preparations; Pharmacotherapy; Phase; Photochemistry; Play; Positioning Attribute; Production; Prognostic Marker; Protein Fragment; Proteins; Proteome; Rest; Role; Sampling; Serologic tests; Serological; Serum; Signal Transduction; Specificity; Stream; T-Lymphocyte; Technology; Testing; Therapeutic; Time; Treatment Efficacy; Trypanosoma cruzi; Work; base; biomarker development; burden of illness; candidate marker; computerized; congenital infection; cost effective; density; design; diagnostic biomarker; disease diagnosis; drug sensitivity; exhaustion; experimental study; feeding; human disease; human pathogen; human subject; improved; individual response; innovation; insight; new technology; next generation; novel; novel diagnostics; novel marker; outcome forecast; pathogen; patient population; patient response; prophylactic; public health relevance; response; scale up; screening; success; tool

 DESCRIPTION (provided by applicant): Trypanosoma cruzi is a parasite responsible for an important human disease, Chagas Disease, which is endemic in the Americas. The parasite is transmitted by the bite of an insect, or by blood transfusion or organ transplants. The current drugs available for treatment are able to cure the disease in its acute phase, and provide benefits to patients in the chronic stage, but certification of cure is difficult to achieve. Management and surveillance of this disease rests heavily on the use of diagnostic tools, which are based on the detection of circulating antibodies against parasite proteins or protein fragments. However, in spite of the availability of a few diagnostic tests for screening blood banks, and for diagnosing the disease, there are major unmet needs in this area. There are currently no biomarkers that can differentially diagnose infections by different parasite strains (which could be linked to drug sensitivity and disease prognosis). Also, there are no tests that provide an early indication of therapeutic treatment success or failure, which constitutes a major obstacle in current drug trials. A constant stream of new biomarkers is required to explore their potential to develop new diagnostic tools. One of the most promising developments in recent years is the ability to produce high-density peptide microarrays, which allow the production of tiling displays of essentially complete pathogen proteomes. The goal of this application is to study the complexity of the human antibody response against this parasite, and to identify thousands of novel serology markers for further characterization. Using high-density peptide microarrays covering the complete Trypanosoma cruzi proteome we will screen sera from diverse Chagas Disease patient populations to identify all antibody- binding protein fragments recognized by these immune responses. This will provide a comprehensive set of novel biomarkers. We will complement this strategy with two comparative studies in which we will seek to define biomarkers that i) are able to differentiate infection by different parasite lineage, and ii) are able to predict treatment success/failure. These studies will feed a pipeline of downstream experiments which will validate these biomarkers for the development of new diagnostic tools.



项目成果

APRANK: Computational Prioritization of Antigenic Proteins and Peptides From Complete Pathogen Proteomes.

• DOI: 10.3389/fimmu.2021.702552
• 发表时间: 2021
• 期刊: Frontiers in immunology
• 影响因子: 7.3
• 作者: Ricci AD;Brunner M;Ramoa D;Carmona SJ;Nielsen M;Agüero F
• 通讯作者: Agüero F

Next-generation ELISA diagnostic assay for Chagas Disease based on the combination of short peptidic epitopes.

• DOI: 10.1371/journal.pntd.0005972
• 发表时间: 2017-10
• 期刊: PLoS neglected tropical diseases
• 影响因子: 3.8
• 作者: Mucci J;Carmona SJ;Volcovich R;Altcheh J;Bracamonte E;Marco JD;Nielsen M;Buscaglia CA;Agüero F
• 通讯作者: Agüero F

Serological Approaches for Trypanosoma cruzi Strain Typing.

Cruzi菌株分型锥虫的血清学方法。

• DOI: 10.1016/j.pt.2020.12.002
• 发表时间: 2021-03
• 期刊: Trends in parasitology
• 影响因子: 9.6
• 作者: Balouz V;Bracco L;Ricci AD;Romer G;Agüero F;Buscaglia CA
• 通讯作者: Buscaglia CA

The Trypanosoma cruzi Antigen and Epitope Atlas: antibody specificities in Chagas disease patients across the Americas.

• DOI: 10.1038/s41467-023-37522-9
• 发表时间: 2023-04-03
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Ricci, Alejandro D.;Bracco, Leonel;Salas-Sarduy, Emir;Ramsey, Janine M.;Nolan, Melissa S.;Lynn, M. Katie;Altcheh, Jaime;Ballering, Griselda E.;Torrico, Faustino;Kesper, Norival;Villar, Juan C.;Marcipar, Ivan S.;Marco, Jorge D.;Aguero, Fernan
• 通讯作者: Aguero, Fernan

High-resolution profiling of linear B-cell epitopes from mucin-associated surface proteins (MASPs) of Trypanosoma cruzi during human infections.

• DOI: 10.1371/journal.pntd.0005986
• 发表时间: 2017-09
• 期刊: PLoS neglected tropical diseases
• 影响因子: 3.8
• 作者: Durante IM;La Spina PE;Carmona SJ;Agüero F;Buscaglia CA
• 通讯作者: Buscaglia CA