Transferred Immunity

转移免疫

基本信息

批准号：
10449295
负责人：
Margaret E Ackerman
金额：
$ 53.86万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
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：
2021-07-12 至 2026-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10449295
关键词：
Affect Affinity Animal Model Antibodies Antibody Repertoire Antibody Therapy Antigens Area Autoimmunity B cell repertoire Binding Biochemical Biodistribution Biological Biology Biophysics Birth Blood Blood specimen Breast Feeding Child Communicable Diseases Coupled Development Engineering Evaluation Fc Receptor Fetal health Fetus Future Genomics Half-Life Health Human Human Milk Humoral Immunities Immunity Immunoglobulin A Immunoglobulin G Immunologics In Vitro Infant Inherited Intrinsic factor Knowledge Lead Link Mass Spectrum Analysis Maternal antibody Maternal-fetal medicine Measurement Mediating Medicine Milk Modeling Molecular Monoclonal Antibody Therapy Morbidity - disease rate Mothers Natural Immunity Neonatal Outcome Pathologic Phenotype Placenta Play Pregnancy Pregnant Women Proteomics Recycling Reporting Resolution Role Sampling Serum Shapes Specificity Techniques Therapeutic antibodies Time Umbilical Cord Blood Vaccinated Vaccination Vaccine Antigen Vaccine Therapy Vaccines Variant Work adaptive immune response antibody engineering antibody transfer critical period design fetal high risk improved in utero in vivo Model in vivo evaluation infant morbidity/mortality innovation insight maternal vaccination molecular phenotype mortality multiple omics natural antibodies neglect neonatal Fc receptor neonatal health neonatal morbidity neonate next generation sequencing non-Native novel novel therapeutics passive antibodies pathogen postnatal protective effect receptor receptor expression response success targeted treatment tissue culture tool unvaccinated vaccine development vaccine immunogenicity vaccine response vaccine-induced antibodies

项目摘要

PROJECT 2 - ABSTRACT This project proposes to better understand the mechanisms governing, and advance our ability to rationally control maternal-fetal antibody transport. By comparing the profiles of antibodies from milk and from blood samples during pregnancy and umbilical cord blood samples after birth using high-throughput proteomic tools such as NextGen sequencing of the maternal B cell repertoire and high-resolution proteomic analysis by mass spectrometry, IgG glycoprofiling, Fc receptor affinity characterization, and Ig isotyping and subclassing, we will define phenotypic biases in global and antigen/ vaccine-specific Ab repertoires transferred to the fetus in vaccinated and unvaccinated pregnancies, and quantify the degree of similarity of the antibody repertoire between mother and child. In vivo evaluation of the relationship between antibody half-life and placental transport in animal models using natural and engineered IgG variants will define the extent of linkage between different biological roles of FcRn, and evaluation of existing and engineering of novel IgG Fc variants for enhanced placental transport in the ex vivo human placenta model will be employed to identify Abs with altered transport phenotypes. Our overarching hypotheses are that among natural and engineered antibody molecules there exist intrinsic biases for certain antibody molecules to transport across placenta more and less efficiently. Discovery and knowledge of these biases will contribute to development of vaccine and therapeutic antibody strategies with increased or decreased transport efficiency that are designed to improve health outcomes for mothers and the fetus/neonate during this critical period of immunological development.

项目2-摘要该项目建议更好地了解管理机制，并提高我们的能力合理控制母体抗体的转运。通过比较牛奶和来自的抗体的曲线怀孕期间的血液样本和脐带血液样本在出生后使用高通量蛋白质组学诸如母体B细胞库的NextGen测序和高分辨率蛋白质组学分析之类的工具。质谱法，IgG糖蛋白酶特性，FC受体亲和力表征以及Ig同分类和亚分类，我们将在转移到胎儿的全球和抗原/疫苗特异性AB曲目中定义表型偏差在接种和未接种疫苗的妊娠中，并量化抗体库的相似程度在母子之间。体内评估抗体半衰期与胎盘之间的关系使用天然和工程IgG变体的动物模型中的运输将定义 FCRN的不同生物学作用，以及对新型IgG FC变体现有和工程的评估将采用体内人胎盘模型中增强的胎盘运输，以识别ABS随着变化的变化运输表型。我们的总体假设是在天然和工程抗体分子中某些抗体分子具有更有效地跨胎盘运输的固有偏见。这些偏见的发现和知识将有助于疫苗和治疗抗体的开发具有提高或降低运输效率的策略，旨在改善健康结果在这个免疫学发展的关键时期，母亲和胎儿/新生儿。