Elimination of flavivirus infected target cells by ADCC

通过 ADCC 消除黄病毒感染的靶细胞

• 批准号: 10057300
• 负责人: Alan L Rothman
• 金额: $ 23.36万
• 依托单位: UNIVERSITY OF RHODE ISLAND
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-22 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10057300
• 关键词: Antibodies; Antibody Specificity; Antibody titer measurement; Antigens; Biological Assay; Cell Line; Cells; Cellular Assay; Cessation of life; Child; Clinical; Cohort Studies; Cytolysis; Data; Dengue; Dengue Infection; Dengue Vaccine; Dengue Virus; Development; Disease; Disease Outcome; Effector Cell; Flavivirus; Flavivirus Infections; Flow Cytometry; Goals; Image Cytometry; Immune; Immune Sera; Immunity; Immunoglobulin Constant Region; Immunoglobulin G; Individual; Infection; Measures; Mediating; Membrane Proteins; Monoclonal Antibodies; NK Cell Activation; Natural Killer Cells; Outcome; Peripheral Blood Mononuclear Cell; Phase; Phase III Clinical Trials; Pilot Projects; Play; Prospective Studies; Prospective cohort; Proteins; Refractory; Reporting; Reproducibility; Role; Sampling; Serotyping; Source; Surface; Thailand; Vaccines; Viral; Viremia; Virus Diseases; ZIKA; Zika Virus; Zika virus vaccine; antibody-dependent cell cytotoxicity; cohort; density; env Gene Products; immunogenic; improved; in vitro Assay; in vivo; mosquito-borne; neutralizing antibody; next generation; novel; pathogenic virus; prospective; vaccine development; vaccine trial

SUMMARY The development and widespread use of a dengue vaccine is required to significantly reduce the global dengue burden. A major goal of vaccine developers is to elicit robust immunity to each of the four antigenically distinct serotypes of dengue since all four serotypes can cause disease and death. It is likely that a zika virus vaccine will be available in the coming years. Pre-existing dengue virus immunity may impact the ability to generate an immunogenic zika vaccine. An improved understanding of the quality of Abs elicited during flavivirus infection is necessary as it is becoming clear that antibody function beyond neutralization is important. For this proposal, we will assess antibody dependent cell mediated cytotoxicity (ADCC) activity of antibodies present in well-defined zika immune sera (with and without previous dengue exposure). We have novel cell lines that enable us to assess the protein specificity of ADCC antibodies and also evaluate both target cell and effector cell activation. We will determine the relationship between antigen density and ADCC antibody titers in the sera. Finally, using pre-infection sera in individuals from Thailand who subsequently developed a subclinical or clinical dengue infection, we will correlate ADCC activity of antibodies with clinical outcome. The studies proposed are important to guide the development of an effective flavivirus vaccine.

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