Transferred Immunity

转移免疫

• 批准号: 10616550
• 负责人: Margaret E Ackerman
• 金额: $ 42.67万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 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/10616550
• 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; 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 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 outcome; 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

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 该项目旨在更好地了解管理机制，并提高我们的能力， 合理控制母胎抗体转运。通过比较牛奶中的抗体和 使用高通量蛋白质组学技术对妊娠期间的血液样本和出生后的脐带血样本进行分析 工具，如母体B细胞库的NextGen测序和高分辨率蛋白质组学分析， 质谱、IgG糖谱分析、Fc受体亲和力表征和IG同种型和亚类， 我们将定义转移至胎儿的总体和抗原/疫苗特异性抗体库中的表型偏倚 在接种疫苗和未接种疫苗的怀孕，并量化抗体库的相似程度 母亲和孩子之间。抗体半衰期和胎盘组织中抗体浓度之间关系的体内评价 使用天然和工程化IgG变体的动物模型中的转运将定义 FcRn的不同生物学作用，以及评价用于免疫调节的新型IgG Fc变体的存在和工程化。 在离体人胎盘模型中增强的胎盘转运将用于鉴定具有改变的 运输表型我们首要的假设是在天然和工程抗体分子中 对于某些抗体分子存在内在的偏向，以更有效或更不有效地转运穿过胎盘。 这些偏差的发现和认识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， 母亲和胎儿/新生儿在免疫发育的这一关键时期。