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Molecular analysis of antibody repertoire elicited after yellow fever vaccination

黄热病疫苗接种后产生的抗体库的分子分析

基本信息

批准号：
10401404
负责人：
Liza Figueiredo Felicori Vilela
金额：
$ 14.42万
依托单位：
FOUNDATION FOR RESEARCH DEVELOPMENT
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-03-01 至 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10401404
关键词：
Acute Affinity African Antibodies Antibody Repertoire Antibody Response Antibody-Dependent Enhancement Attenuated B-Lymphocytes Binding Biological Assay Brazil Case Fatality Rates Cessation of life Chills Country Data Dengue Infection Dengue Virus Development Disease Disease Outbreaks Epidemic Epitopes Exhibits Family Fever Flavivirus Frequencies Future Generations Geographic Locations Headache Health Hemorrhage Human Immune Sera Immunoglobulin G In Vitro Incidence Infection Institution Lead Legal patent Maps Medical Memory B-Lymphocyte Methods Molecular Molecular Analysis Monoclonal Antibodies Mutagenesis Myalgia Nature Nausea Pathogenicity Patients Pattern Peripheral Persons Physiological Plasmablast Preventative vaccination Proteins Publishing Recombinant Proteins Reporting Serology Serum Shotguns Specificity Structure Symptoms Techniques Testing Therapeutic Therapeutic Monoclonal Antibodies Vaccinated Vaccination Vaccinee Vaccines Virus Work Yellow Fever Yellow Fever Vaccine Yellow Fever Virus Infection Yellow fever virus ZIKV infection Zika Virus adaptive immune response austin authority base cohort cross immunity cross reactivity design disorder prevention exhaustion flu in vitro activity in vivo innovation insight interdisciplinary approach liver injury member neutralizing antibody next generation sequencing novel therapeutics novel vaccines prophylactic rational design renal damage response therapeutic development tool unvaccinated vaccination strategy vaccine development

项目摘要

Molecular analysis of antibody repertoire elicited after yellow fever vaccination Even though an effective vaccine against the yellow fever virus (YFV) exist a high frequency of global YFV outbreaks represent an imminent threat to human health. Health authorities have confirmed more than 500 deaths just in Brazil in the last two years, and more than 150 incidents of YFV outbreaks in 26 African countries were reported to the WHO in the last 30 years. YFV infection causes a febrile flu-like illness, and about 10-25% of patients develop hemorrhagic manifestations, kidney and liver damage that can result in death. YFV show similarities compared to other medical important flavivirus as dengue virus (DENV) and zika virus (ZIKV). The central hypothesis underlying the proposed work is that in geographic regions where YFV co-circulates with DENV and ZIKV endemic flaviviruses, cohorts vaccinated for YFV will exhibit a statistically different pattern of incidence of DENV and ZIKV infections (significantly lower or greater) compared to unvaccinated controls, due to vaccine elicitation of serum IgG antibodies cross-reactive between YFV and DENV and/or ZIKV. In view of this, the aims of this collaborative project are to: (i) inform on the complexity and molecular features of the antibody repertoire elicited by YFV vaccination that are specific to YFV and those that cross-react with DENV-2 and/or ZIKV, (ii) isolate YFV-specific monoclonal antibodies (mAbs) with therapeutic potential, (iii) evaluate the ability of these mAbs to protect against YFV, DENV and ZIKV infections or to increase the infection through antibody dependent enhancement (ADE), and (iv) identify the epitopes targeted by the neutralizing and cross-reactive mAbs. Our multidisciplinary approach will include a set of original tools for analyzing adaptive immune responses— developed, published, and protected by two issued US patents and currently available only at UT Austin—to comprehensively identify, at high throughput, high-affinity human cross-reactive serum antibodies and delineate the molecular nature of cross-reactive antibody generation. Collectively, this work will be important to determine the existence of ADE-induced by YFV vaccination and to open up the perspectives to develop vaccination strategies that minimize ADE responses between YFV, ZIKV and DENV and also the development of effective mAb therapeutics against Yellow Fever.

黄热病疫苗接种后抗体库的分子分析