Transferred Immunity

项目2--摘要 这个项目建议更好地了解治理机制，并提高我们的能力 合理控制母胎抗体转运。通过比较牛奶和牛奶中的抗体图谱 用高通量蛋白质组学方法检测孕期和产后脐血样本 工具，如母体B细胞库的NextGen测序和高分辨率蛋白质组分析 质谱学，免疫球蛋白糖谱，Fc受体亲和力鉴定，和Ig同种分型和亚类， 我们将定义转移到胎儿的全局性和抗原/疫苗特异性抗体谱系中的表型偏见 在接种疫苗和未接种疫苗的怀孕中，并量化抗体谱系的相似程度 在母亲和孩子之间。抗体半衰期与胎盘关系的体内评价 在使用天然和工程免疫球蛋白变体的动物模型中的转运将确定两者之间的联系程度 FcRN的不同生物学作用，以及对新的免疫球蛋白Fc变异体的现有和工程的评估 体外人胎盘模型中增强的胎盘转运将被用来识别发生改变的抗体 运输表型。我们的主要假设是，在天然抗体分子和基因工程抗体分子中 某些抗体分子在胎盘间的转运效率较高或较低，存在固有的偏差。 对这些偏向的发现和了解将有助于疫苗和治疗性抗体的开发 提高或降低运输效率的战略，旨在改善以下方面的健康结果 母亲和胎儿/新生儿在这一免疫学发展的关键时期。

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.