Seriodiagnostic arrays for biodefense and emerging infectious diseases

用于生物防御和新发传染病的血清诊断阵列

• 批准号: 7649416
• 负责人: David Huw Davies
• 金额: $ 100万
• 依托单位: IMMPORT THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-06-15 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7649416
• 关键词: Affinity; Algorithms; Amendment; Antibodies; Antigens; Award; Bacteria; Bioinformatics; Biological Assay; Biological Products; Biological Warfare; Biomedical Research; California; Categories; Centers for Disease Control and Prevention (U.S.); Clinical; Clinical Research; Collaborations; Data; Data Set; Developed Countries; Developing Countries; Development; Diagnosis; Diagnostic; Diagnostic Procedure; Diagnostic Reagent; Diagnostic Services; Diagnostic tests; Disease; Emerging Communicable Diseases; Equipment and supply inventories; Evaluation; Exanthema; Genes; Head; Health; Herpesviridae; Housing; Human; Immune response; Immunodominant Antigens; Individual; Infection; Infectious Agent; Laboratories; Licensure; Methods; Monitor; Organism; Orthopoxvirus; Parasites; Phage Display; Pharmacologic Substance; Phase; Physicians; Pregnancy; Prevalence; Principal Investigator; Printing; Protein Array; Protein Microchips; Proteins; Proteome; Proteomics; Public Health; Reagent; Research; Research Infrastructure; Screening procedure; Serodiagnoses; Serologic tests; Serological; Serum; Services; Small Business Innovation Research Grant; Specificity; Specimen; Staging; Subunit Vaccines; Test Result; Testing; Therapeutic; Universities; Vaccine Antigen; Vaccinia; Vaccinia virus; Virus; Work; base; biodefense; gene cloning; improved; manufacturing facility; microbial; novel diagnostics; novel vaccines; pathogen; programs; protein expression; protein purification; prototype; public health relevance; response

DESCRIPTION (provided by applicant): In Phase I of this SBIR, ImmPORT Therapeutics and the UCI Proteomics Core developed a high throughput gene cloning and protein expression platform that allowed the proteomes of any sequenced infectious agent to be expressed and printed onto microarray chips. Since Phase I we have cloned and expressed ~15,000 genes from nearly 20 different pathogens associated with biodefense and emerging infectious diseases. By probing the arrays with sera from individuals with well-defined clinical stages of infection, we have built up a vast dataset concerning which antibodies are present in different stages of disease. By using statistical and bioinformatic algorithms, we can derive antigen sets that, when combined, can provide the basis for serological tests able to discriminate between different infections, or even between different stages of the same infection. Phase II, ImmPORT will establish a GMP manufacturing facility and a Clinical Research Lab to offer diagnostic products and services to developers of novel vaccines, physicians and Phama. At the head of a product pipeline will be serodiagnostic immunostrips that will be evaluated for discriminating orthopoxvirus infections from clinically similar rash infections and for diagnosing TORCH infections associated with problems during pregnancy. Aim 1: Clone an additional 2000 genes from various rash causing organisms and combine these with an existing inventory of orthopoxvirus and herpes viruses. These will printed on arrays and, in collaboration with colleagues at the CDC, arrays will be probed with well characterized sera to define immunodominant and serodiagnostic antigens. From these data we will produce prototype immunostrips for manufacture and evaluation at CDC. Aim 2: Establish a GMP protein purification and diagnostic reagent manufacturing facility at ImmPORT. The facility will manufacture protein arrays and immunostrips for its Clinical Research Laboratory , and assay kits that will be sold to biomedical research labs and reference laboratories, and as a pivotal FDA-required assay to support licensure of clinical products. Aim 3. Establish a Clinical Research Laboratory at ImmPORT to offer serodiagnostic testing services that will operate in compliance with the Clinical Laboratory Improvement Amendment (CLIA) to be certified to perform validated testing on human specimens for diagnosis, and to provide FDA compliant test results to support licensure of clinical products. With the establishment of a manufacturing infrastructure at ImmPORT, the company's high throughput antigen discovery platform will continue to rapidly identify candidate antigens for development of other serodiagnostics and subunit vaccine products for category A, B and C biological agents and well as other emerging infectious diseases of importance to human health. Project Narrative With support from a phase I SBIR, ImmPORT Therapeutics and the Proteomics Core Lab UCI developed a method for screening the whole proteomes of infectious organisms for diagnostic and vaccine antigens. In Phase II, ImmPORT will establish a GMP manufacturing facility and a Clinical Research Lab to offer diagnostic products and services to developers of novel vaccines, physicians and Phama. At the head of a product pipeline will be serodiagnostic immunostrips that will be evaluated for discriminating orthopoxvirus infections from clinically similar rash infections and for diagnosing TORCH infections associated with problems during pregnancy. PUBLIC HEALTH RELEVANCE With support from a phase I SBIR, ImmPORT Therapeutics and the Proteomics Core Lab UCI developed a method for screening the whole proteomes of infectious organisms for diagnostic and vaccine antigens. In Phase II, ImmPORT will establish a GMP manufacturing facility and a Clinical Research Lab to offer diagnostic products and services to developers of novel vaccines, physicians and Phama. At the head of a product pipeline will be serodiagnostic immunostrips that will be evaluated for discriminating orthopoxvirus infections from clinically similar rash infections and for diagnosing TORCH infections associated with problems during pregnancy.

描述（由申请人提供）：在本SBIR的第一阶段，ImmPORT Therapeutics和UCI Proteomics Core开发了一个高通量基因克隆和蛋白质表达平台，允许任何已测序的传染病原的蛋白质组表达并打印到微阵列芯片上。自第一阶段以来，我们已经克隆并表达了来自近20种与生物防御和新兴传染病相关的不同病原体的约15，000个基因。通过用来自具有明确定义的感染临床阶段的个体的血清探测阵列，我们已经建立了一个关于哪些抗体存在于疾病的不同阶段的庞大数据集。通过使用统计和生物信息学算法，我们可以推导出抗原集，当结合时，可以为能够区分不同感染甚至同一感染的不同阶段的血清学测试提供基础。在第二阶段，ImmPORT将建立一个GMP生产设施和一个临床研究实验室，为新型疫苗的开发人员、医生和Phama提供诊断产品和服务。在产品管道的头部将是血清诊断免疫条，将被评估用于区分正痘病毒感染与临床相似的皮疹感染，并诊断与妊娠期间问题相关的TORCH感染。目标1：从各种引起皮疹的生物体中克隆另外2000个基因，并将这些基因与现有的正痘病毒和疱疹病毒的库存联合收割机结合起来。这些将打印在阵列上，并与CDC的同事合作，将用充分表征的血清探测阵列，以确定免疫显性和血清诊断抗原。根据这些数据，我们将生产原型免疫试纸，用于CDC的生产和评估。目标2：在ImmPORT建立GMP蛋白纯化和诊断试剂生产设施。该工厂将为其临床研究实验室生产蛋白质阵列和免疫条，并将向生物医学研究实验室和参考实验室出售检测试剂盒，并作为FDA要求的关键检测试剂盒，以支持临床产品的许可。目标3。在ImmPORT建立一个临床研究实验室，提供血清诊断检测服务，该服务将按照临床实验室改进修正案（CLIA）进行操作，以获得认证，对人类样本进行经验证的诊断检测，并提供符合FDA要求的检测结果，以支持临床产品的许可证。随着ImmPORT生产基础设施的建立，该公司的高通量抗原发现平台将继续快速鉴定候选抗原，用于开发其他血清诊断和亚单位疫苗产品，用于A、B和C类生物制剂以及其他对人类健康具有重要意义的新兴传染病。在I期SBIR的支持下，ImmPORT Therapeutics和蛋白质组学核心实验室UCI开发了一种用于筛选感染性生物体的全蛋白质组以获得诊断和疫苗抗原的方法。在第二阶段，ImmPORT将建立一个GMP生产设施和一个临床研究实验室，为新型疫苗开发人员、医生和制药公司提供诊断产品和服务。在产品管道的头部将是血清诊断免疫条，将被评估用于区分正痘病毒感染与临床相似的皮疹感染，并诊断与妊娠期间问题相关的TORCH感染。公共卫生相关性在I期SBIR的支持下，ImmPORT Therapeutics和UCI蛋白质组学核心实验室开发了一种方法，用于筛选传染性生物体的全蛋白质组，以获得诊断和疫苗抗原。在第二阶段，ImmPORT将建立一个GMP生产设施和一个临床研究实验室，为新型疫苗开发人员、医生和制药公司提供诊断产品和服务。在产品管道的头部将是血清诊断免疫条，将被评估用于区分正痘病毒感染与临床相似的皮疹感染，并诊断与妊娠期间问题相关的TORCH感染。