Prediction and Perturbation of Epitopes by Modeling and Immune Responses

通过建模和免疫反应预测和扰动表位

基本信息

批准号：
8897074
负责人：
WILLIAM R. SCHIEF
金额：
$ 53.07万
依托单位：
VANDERBILT UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至 2016-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8897074
关键词：
Affect Algorithm Design Algorithms Antibodies Antibody Response Antibody Specificity Antigen Targeting Antigen-Antibody Complex Antigens Back Benchmarking Binding Binding Sites Biochemical Biological Models Cell surface Characteristics Clinical Collaborations Communicable Diseases Complex Computer Simulation Computing Methodologies Data Data Set Databases Dengue Dengue Virus Development Distal Ebola virus Engineering Ensure Epitopes Evaluation Glycoproteins Head Human Immune response Immune system Immunity Immunization Immunology In Vitro Infection Influenza Hemagglutinin Investigation Libraries Maps Medical Methods Modeling Monoclonal Antibodies Mus Polysaccharides Property Proteins Protocols documentation Reproduction Serum Specificity Structural Models Structure Surface Surface Properties Techniques Testing Vaccination Vaccine Antigen Vaccines Viral Viral Antigens Virus base biodefense design feeding human subject improved influenzavirus method development model design neutralizing monoclonal antibodies novel novel vaccines pathogen receptor binding research study response vaccine development

项目摘要

This project (Project 3 of a three project proposal entitled "Structure based design of antibodies and vaccines" responding to the RFA-AI-14-028 “Modeling Immunity for Biodefense”) will develop computational methods to predict the epitope specificity of antibody immune responses to structural antigens, will develop computational methods to design structurally stable antigens with customized surfaces to enable focusing of antibody immune responses to preselected epitopes, and will test these methods by experiment, by assessing immune responses to designed model antigens. The primary model system will be the head domain of influenza hemagglutinin and the focus will be on the epitopes within and around the receptor binding site, but other model systems will include neutralizing epitopes of glycoproteins from dengue virus and ebola virus. To assist computational methods development, in vitro cell surface display methods will be employed to improve the properties of designed antigens, and those results will feed back to guide algorithmic improvements. Likewise, results from immunization studies will feed back to guide refinement of the methods. The project 3 specific aims are: (1) Develop and benchmark computational methods to predict epitope immuno-visibility (2) Develop computational methods to design structurally stable epitope-focused immunogens and experimentally test those methods by evaluating immune responses to designed model antigens (3) Develop computational methods to resurface immunogens to focus immune responses to preselected epitopes, and test those methods by evaluating immune responses to designed model antigens. .

该项目（三个项目提案的项目3，标题为“基于结构的设计抗体和疫苗”对RFA-AI-14-028的反应” Biodefense”）将开发计算方法来预测的表位特异性对结构抗原的抗体免疫回应将开发计算方法设计具有自定义表面的结构稳定抗原抗体免疫反应对呈现的表位，并将通过实验，通过评估对设计模型抗原的免疫反应。主要模型系统将成为造成影响力的hemagglutinin的头部领域，重点将是在受体结合位点内外的表位上，其他模型系统将包括从登革热病毒和埃博拉病毒中中和糖蛋白的表位。到协助计算方法开发，体外细胞表面显示方法将是用于改善设计抗原的特性，这些结果将进食返回指导算法改进。同样，免疫研究的结果也将回馈以指导方法的细化。项目3的特定目的是：（1）开发和基准计算方法来预测表位免疫可见性（2）开发计算方法来设计以结构稳定的表位为中心免疫原生物和实验测试这些方法，通过评估免疫回报设计的模型抗原（3）开发了用于恢复免疫原的计算方法将免疫反应集中在提出的表位上，并通过评估对设计模型抗原的免疫反应。。