Antibody and Reagent Development Core

抗体和试剂开发核心

• 批准号: 10555053
• 负责人: Daisy W Leung
• 金额: $ 53.16万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-07 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10555053
• 关键词: A549; Address; Antibodies; Antibody Formation; Antibody Specificity; Antigens; Biochemical; Biological Assay; Case Fatality Rates; Category A pathogen; Cell Culture Techniques; Cell Line; Cells; Collaborations; Communities; Complex; Consultations; DNA; Deposition; Development; Ebola; Ebola virus; Engineering; Ensure; Enzyme-Linked Immunosorbent Assay; Evaluation; Exhibits; Filovirus; Funding; Generations; Genes; Genome; Genome engineering; Goals; Hela Cells; Human; Hybridomas; Immune Evasion; Immune system; Immunize; Immunofluorescence Immunologic; Immunoglobulin G; Immunoprecipitation; In Vitro; Infection; Injections; Integration Host Factors; Knock-out; Knockout Mice; Leadership; Luciferases; Marburgvirus; Methods; Mission; Modeling; Molecular; Monoclonal Antibodies; Mus; National Institute of Allergy and Infectious Disease; Pathogenesis; Pathway interactions; Peptide antibodies; Phage Display; Phosphorylation; Polymerase; Positioning Attribute; Post-Translational Protein Processing; Proteins; Reagent; Recombinants; Research Project Grants; Resources; Role; Standardization; System; Technology; Transgenic Animals; Vaccines; Validation; Viral; Viral Antibodies; Viral Proteins; Virus; Virus Replication; Western Blotting; Work; antibody engineering; antiviral drug development; cell type; conditional knockout; experimental study; flexibility; induced pluripotent stem cell; innovation; knockout animal; mouse model; nonhuman primate; protein protein interaction; synthetic antibodies

Core B - Project Summary/Abstract Filoviruses, which are NIAID category A priority pathogens, can subvert host immune systems to facilitate viral replication, resulting in human case fatality rates as high as 90%. The filoviral genome encodes for seven to nine proteins. Despite the small number of genes, limited information is available on the specific mechanisms by which different viral-viral and viral-host interactions contribute to filoviral replication and pathogenesis, hindering the development of antivirals or vaccines. The Antibody and Reagent Development Core (Core B) will provide critical reagents and support for the overall scientific mission and facilitate the characterization of these interactions. Specifically, Core B will provide a unique set of standardized antibodies, cell-lines, and mouse models that will be disseminated amongst the Research Projects (RPs) and Cores of the PPG. In consultation with the Administrative Core (Core A) and the PPG leadership, Core B will prioritize experiments to ensure that reagents will be readily available to the RPs and Cores for use, validation, and characterization of interfaces between viral proteins and host factors that impact steps in the filoviral replication cycle. Core B will develop mouse monoclonal and synthetic antibodies against Ebola and Marburg viral proteins, generate knockout cell lines of host factors, and generate conditional knockout mouse models of select host factors identified by RP01, RP02, RP03, and Core C when such reagents are not commercially available. Given the need for a unified reagent development pipeline, the scientific core activity for Core B is justified.

核心B -项目总结/摘要 丝状病毒是NIAID A类优先病原体，可以破坏宿主免疫系统，以促进病毒感染。 复制，导致人类病例死亡率高达90%。丝状病毒基因组编码7到9个 proteins.尽管基因的数量很少，但通过以下方式获得的关于特定机制的信息有限： 不同的病毒-病毒和病毒-宿主相互作用有助于丝状病毒的复制和发病，阻碍 抗病毒药物或疫苗的发展。抗体和试剂开发核心（核心B）将提供 关键试剂和支持整个科学使命，并促进这些表征 交互.具体而言，核心B将提供一组独特的标准化抗体、细胞系和小鼠免疫原性。 这些模型将在研究项目（RP）和PPG核心之间传播。协商 在行政核心（核心A）和项目设计小组领导层的配合下，核心B将优先进行试验，以确保 RP和核心将随时可获得试剂，用于接口的使用、验证和表征 病毒蛋白质和宿主因子之间的关系，影响丝状病毒复制周期中的步骤。核心B将开发 针对埃博拉和马尔堡病毒蛋白的小鼠单克隆抗体和合成抗体，产生敲除细胞 系的宿主因子，并产生由RP 01鉴定的选择宿主因子的条件性敲除小鼠模型， RP 02、RP 03和核心C（当此类试剂不可商购时）。鉴于需要一个统一的 试剂开发管线，核心B的科学核心活动是合理的。