Seriodiagnostic arrays for biodefense and emerging infectious diseases

描述(申请人提供)：在这项SBIR的第一阶段，ImmPORT Treeutics和UCI蛋白质组学核心开发了一个高通量的基因克隆和蛋白质表达平台，允许表达任何已测序的感染性病原体的蛋白质组并将其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近20种不同病原体的约15,000个基因，这些病原体与生物防御和新出现的传染病有关。通过探测来自感染临床阶段明确的个体的血清阵列，我们已经建立了关于不同疾病阶段存在哪些抗体的海量数据集。通过使用统计和生物信息学算法，我们可以得出抗原集，当这些抗原集结合在一起时，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。第二阶段，ImmPORT将建立GMP生产设施和临床研究实验室，向新型疫苗开发商、医生和Phama提供诊断产品和服务。在产品线的最前面将是血清诊断免疫试条，将被评估用于区分正痘病毒感染和临床上类似的皮疹感染，并用于诊断与怀孕期间的问题相关的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库存相结合。这些将打印在阵列上，并与疾控中心的同事合作，将用特征良好的血清来探测阵列，以确定免疫优势抗原和血清诊断抗原。根据这些数据，我们将生产用于疾控中心制造和评估的免疫试条原型。目的2：在ImmPORT建立GMP蛋白纯化和诊断试剂生产设施。该设施将为其临床研究实验室制造蛋白质阵列和免疫条，以及将出售给生物医学研究实验室和参考实验室的检测试剂盒，并作为FDA要求的关键检测方法，以支持临床产品的许可。目的3.在ImmPORT建立一个临床研究实验室，提供血清诊断测试服务，该服务将按照《临床实验室改进修正案》(CLIA)进行认证，以对用于诊断的人体样本进行验证测试，并提供符合FDA标准的测试结果，以支持临床产品的许可。随着ImmPORT制造基础设施的建立，该公司的高通量抗原发现平台将继续快速识别候选抗原，用于开发A、B和C类生物制剂的其他血清诊断和亚单位疫苗产品，以及其他对人类健康具有重要意义的新出现的传染病。项目叙述在第一阶段SBIR、ImmPORT治疗公司和UCI蛋白质组学核心实验室的支持下，开发了一种为诊断和疫苗抗原筛选感染生物体的整个蛋白质组的方法。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，向新型疫苗开发商、医生和Phama提供诊断产品和服务。在产品线的最前面将是血清诊断免疫试条，将被评估用于区分正痘病毒感染和临床上类似的皮疹感染，并用于诊断与怀孕期间的问题相关的TORCH感染。公共卫生相关性在第一阶段SBIR、ImmPORT治疗公司和UCI蛋白质组学核心实验室的支持下，开发了一种对感染生物的整个蛋白质组进行诊断和疫苗抗原筛选的方法。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，向新型疫苗开发商、医生和Phama提供诊断产品和服务。在产品线的最前面将是血清诊断免疫试条，将被评估用于区分正痘病毒感染和临床上类似的皮疹感染，并用于诊断与怀孕期间的问题相关的TORCH感染。

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.