Antibody Cooperation mediated by Fc-gamma Receptor (FcyR)-bearing cells

由 Fc-gamma 受体 (FcyR) 携带细胞介导的抗体合作

• 批准号: 9140252
• 负责人: Guido Ferrari
• 金额: $ 56.17万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-01 至 2021-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9140252
• 关键词: Active Immunization; Antibodies; Antibody Response; Antibody Specificity; Antigen-Antibody Complex; Antiviral Agents; Cells; Complement; Data; Effector Cell; Epitopes; Equilibrium; Fc Receptor; Frequencies; Genetic; Genotype; HIV; HIV-1; Human; IgG Receptors; IgG1; IgG3; IgG4; Immunization; Immunoglobulin A; Infection; Infection Control; Intervention; Lead; Measures; Mediating; Memory; Modeling; Natural Killer Cells; Nature; Outcome; Phagocytosis; Phenotype; Plasma; Play; Recruitment Activity; Regimen; Reporting; Risk; Role; SIV; Serum; Specificity; Testing; Vaccination; Vaccines; Variant; Viral Antibodies; Viral Physiology; Virion; antibody-dependent cell cytotoxicity; base; cell type; crosslink; glycosylation; improved; monocyte; neutralizing antibody; neutrophil; nonhuman primate; novel; programs; response; vaccine efficacy; vaccine trial

Project 2. Antibody Cooperation for Fc-Fc-gamma Receptor (FcγR)-mediated functions. Although intrinsic differences in Fc-FcR interactions exist between humans and RM, we hypothesize that similarities between the two species for engagement of the FcγR-bearing cells can be defined to 1) select RM with FcγR genotypes/phenotypes mediating antiviral functions that match those observed in humans; and 2) identify combinations of antibodies of multiple specificities, through highly selective Fc- FcγR antibody interactions, that can act in concert to recruit Fc-gamma R-bearing cells similar to humans The overall Program hypothesis is that the RM model can be substantially improved for testing antibody-based interventions and vaccines through elucidation of key variables that impact species-specific FcgR-dependent effector functions (i.e. antibody epitope specificity, immune complex formation, isotype/subclass, glycosylation, and FcR genotype/phenotype. The specific aims for Project 2 are as follows: AIM 1. Define similarities and differences in FcγR mediated Ab effector function between RM and humans. AIM 2. Determine the combination of antibodies that together can mediate superior antiviral function

项目2. Fc-Fc-γ受体（FcγR）介导功能的抗体协同作用。 尽管人和RM之间存在Fc-FcR相互作用的内在差异，但我们假设， 两个物种之间在Fcγ R携带细胞接合方面的相似性可定义为1） 选择具有FcγR基因型/表型介导抗病毒功能的RM，这些基因型/表型与 人;和2）通过高度选择性的Fc- FcγR抗体相互作用，可协同作用以招募与人类相似的携带Fc γ R的细胞 总体计划假设是，RM模型可以得到实质性改进，用于检测基于抗体的 通过阐明影响物种特异性FcgR依赖性的关键变量， 效应子功能（即抗体表位特异性，免疫复合物形成，同种型/亚类，糖基化， 和FcR基因型/表型。 项目2的具体目标如下： AIM 1.定义RM和RM之间FcγR介导的Ab效应子功能的相似性和差异 人类 AIM 2.确定能够共同介导上级抗病毒功能的抗体组合