Innovative Approach to Assay Development for the Diagnosis of Invasive Aspergillo

侵袭性曲霉诊断检测方法开发的创新方法

• 批准号: 8073569
• 负责人: Kimberly E. Hanson
• 金额: $ 21.16万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8073569
• 关键词: Address; Alveolar; Animal Diseases; Animal Model; Antibodies; Antifungal Therapy; Antigens; Aspergillosis; Aspergillus; Aspergillus fumigatus; Atomic Force Microscopy; Benzoates; Biological Assay; Biological Markers; Body Fluids; Bovine Serum Albumin; Cavia; Chronic Granulomatous Disease; Clinical; Clinical Sensitivity; Communicable Diseases; Complement; Coupled; Detection; Development; Diagnosis; Diagnostic; Diagnostic tests; Disease; Early Diagnosis; Feline Calicivirus; Fungal Antigens; Generations; Goals; Gold; Growth; Hand; Hematopoietic Stem Cell Transplantation; Human; Immunoassay; Immunocompromised Host; Immunologist; Immunosuppression; Individual; Infection; Institutes; Institutional Review Boards; Irrigation; Label; Laboratories; Measurement; Medical; Metric; Monitor; Monoclonal Antibodies; Morbidity - disease rate; Mycobacterium avium; Mycoses; North Dakota; Onset of illness; Outcome; Paratuberculosis; Patients; Performance; Phase; Polyenes; Prostate-Specific Antigen; Proteins; Protocols documentation; Raman Spectrum Analysis; Reporter; Reporting; Reproduction spores; Research; Rotation; Sampling; Scanning Electron Microscopy; Scientist; Screening procedure; Sensitivity and Specificity; Set protein; Signal Transduction; Specificity; Staging; Surface; Techniques; Testing; The science of Mycology; Therapeutic; Time; Triazoles; Universities; Utah; Validation; Virus; Work; acronyms; assay development; base; combat; design; dithiobis(succinimidylpropionate); galactomannan; human disease; improved; infrared spectroscopy; innovation; mRNA Differential Displays; meetings; mortality; nanoparticle; novel; pathogen; patient oriented research; polyglucosan; prognostic; tool

DESCRIPTION (provided by applicant): Invasive Aspergillosis (IA) is a devastating and frequently fatal infection in immunocompromised patients, in part because of poor early detection tools. The ability to promptly launch antifungal therapy for Aspergillosis and other invasive fungal diseases is critical for positive patient outcomes. However, early detection is complicated by low levels of antigenic markers that signal disease onset and by poor specificity of current diagnostic assays. The aim of this proposal is to develop an antibody-based diagnostics platform comprised of new monoclonal antibodies coupled with the ultrasensitive detection capabilities of surface enhanced Raman spectroscopy and gold nanoparticle sandwich assays. To address the challenges in the early detection of IA, we have assembled a collaborative research team of scientists from the University of Utah and North Dakota State University composed of immunologists with expertise in monoclonal antibody development and screening for Aspergillus spp; medical microbiologists with strengths in basic mycology, fungal assay development and validation; analytical chemists with a strong focus in the creation of novel, ultrasensitive and selective diagnostic tests; and infectious disease clinicians with proficiency in the design and implementation of patient-oriented research. We will address the specific aims of this project in two phases. The aims for the R21 phase of the project are: (1) Identify protein-based fungal targets through the development of monoclonal antibodies from unique, stage-specific biomarkers of Aspergillus spp. (2) Evaluate monoclonal antibody combinations with surface enhanced Raman spectroscopy-based sandwich immunoassay techniques. (3) Define assay performance metric comparisons using diverse human sample matrices. Upon meeting the milestones of the first stage of the project, the aims of the R33 phase are: (1) Characterize fungal target proteins based on growth stage specificity. (2) Optimize analysis protocols to maximize fungal detection. (3) Standardize components of a unique analysis kit for early clinical Aspergillosis diagnosis. The detection strategy created through the successful completion of this project will redefine the diagnosis of IA through augmented sensitivity and specificity, permitting treatment at the earliest stages of disease.

描述（由申请人提供）：侵袭性曲霉病（IA）是免疫功能低下患者的一种破坏性且经常致命的感染，部分原因是早期检测工具不完善。及时启动抗真菌治疗曲霉病和其他侵袭性真菌疾病的能力对患者的积极结果至关重要。然而，早期检测由于表明疾病发病的抗原标记物水平低以及当前诊断分析的特异性差而变得复杂。该提案的目的是开发一种基于抗体的诊断平台，该平台由新的单克隆抗体结合表面增强拉曼光谱和金纳米颗粒夹心测定的超灵敏检测能力组成。为了应对早期发现IA的挑战，我们组建了一个由犹他大学和北达科他州的科学家组成的合作研究小组