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Structure-Function Analytics Core

结构-功能分析核心

基本信息

批准号：
10670249
负责人：
GEORGIA Doris TOMARAS
金额：
$ 100.92万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-25 至 2026-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10670249
关键词：
Animal Model Antibodies Antibody Response Antigen-Antibody Complex Antigens Architecture Binding Biochemical Biological Biological Models Biology Biophysics Blood Cells Characteristics Clinic Complex Computing Methodologies Data Data Analyses Dissection Effector Cell Epitopes Extracellular Domain Fc Receptor Fc(alpha) receptor Gene Expression Profiling Genetic Transcription Goals HIV Antibodies HIV-1 High Pressure Liquid Chromatography Human Immune Immunoglobulin A Immunoglobulin G Immunoglobulins Immunologic Receptors In Situ In Vitro Infection Inflammation Infusion procedures Knowledge Lead Macaca mulatta Maps Mediating Methods Modeling Molecular Monoclonal Antibodies Outcome Peptides Phenotype Play Polymeric Immunoglobulin Receptors Polysaccharides Population Post-Translational Protein Processing Recombinants Regimen Resolution Role Sampling Specificity Standardization Structure Therapeutic Studies Tissues Translating Vaccine Design Vaccines Variant Viral Viral Antibodies Viral Load result Viral Physiology cell type data integration diverse data env Gene Products experimental study glycosylation human model immunoprophylaxis in vivo insight interest mouse model neonatal Fc receptor nonhuman primate polyclonal antibody programs protective efficacy receptor receptor binding response vaccine trial

项目摘要

ABSTRACT_Core 2 Considerable evidence suggests a role for diverse antibody (Ab) activities, including Fc receptor (FcR)- mediated functions in viral load reduction and in blocking HIV-1 acquisition. Although the role of FcR-effector function in antiviral activity holds across multiple model systems and Abs, mechanistic insights are complicated by species-specific solutions to balancing potent Ab effector activity with damaging inflammation, distinct epitope-, effector-, and Ab-specific factors, as well as distinctions between the effector mechanisms available in blood and tissue. Despite evolutionary proximity, significant differences between Rhesus macaque (RM) and human Ab biology that manifest in different functional characteristics of the Ab isotypes and subclasses, FcRs expressed on innate immune cells, and their biological interplay. This program will expand this map of how antiviral activity against HIV-1 is accomplished by diverse effector mechanisms, involving engagement of different soluble factors and effector cell populations, and distinctive immunoglobulin types in immune-complexes that vary in their overall architecture and biological activity, in both humans and RM. There is a continuing need to define this biology in humans and animal models in order to effectively translate insights gained from emerging protective and therapeutic studies to the clinic, and fuel impactful Ab immunoprophylaxis, cure strategies, and vaccine designs. The Structure-Function Analytics Core will support Projects 1, 2, and 3 and play a key role in achieving Program Goals by providing unifying structural, biophysical, biochemical, and data analysis of the Ab features and Fv and Fc interactions that underpin potent antiviral activities. Aim 1. Define the biophysical basis of potent antiviral Ab activity. Aim 2: Define the structural basis of potent antiviral Ab activity. Aim 3. Model the knowledge of immune cells and Ab features to define optimal antiviral activities.

ABSTRACT_Core 2