Maternal Immunization and Determinants of Infant Immunity

母亲免疫接种和婴儿免疫的决定因素

• 批准号: 10203485
• 负责人: Marcela F Pasetti
• 金额: $ 318.86万
• 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/10203485
• 关键词: 5 year old; Address; Adult; Affect; Animal Model; Antibodies; Antibody-mediated protection; Biophysics; Cause of Death; Cells; Child; Childhood; Clinical; Communicable Diseases; Complex; Data Analyses; Data Science; Data Set; Development; Effectiveness; Environment; Goals; Health; Human Milk; Immune; Immune response; Immune system; Immunity; Immunization; Immunobiology; Immunologics; Immunology; Immunotherapy; In Vitro; Infant; Infant Health; Infection; Infectious Agent; Infectious Disease Immunology; Influenza; Intervention; Intrinsic factor; Knowledge; Learning; Life; Link; Logistics; Maternal Health; Maternal and Child Health; Maternal antibody; Maternally-Acquired Immunity; Mediating; Methods; Molecular; Monoclonal Antibodies; Morbidity - disease rate; Mothers; Newborn Infant; Pathway interactions; Pertussis; Placenta; Predisposition; Pregnancy; Pregnant Women; Productivity; Public Health; Quality Control; Research; Research Personnel; Role; Series; Serology; Specimen; Structure; System; T cell response; Technology; Tetanus; Time; Tissue Model; Training; Vaccination; Vaccine Design; Vaccines; analytical tool; antibody engineering; antibody transfer; cohort; data dissemination; data management; fitness; human tissue; improved; infection burden; insight; interest; longitudinal analysis; low and middle-income countries; maternal vaccination; mortality; multidisciplinary; multimodality; neonatal immunity; novel; pathogen; predicting response; prevent; programs; response; success; translational research program; vaccine response; vaccine-induced antibodies; vaccine-induced immunity; vaccinology

OVERALL ABSTRACT – MATERNAL IMMUNIZATION AND DETERMINANTS OF INFANT IMMUNITY (MADI) Infectious diseases remain the leading cause of death in children under 5 years worldwide. The most affected are newborns and infants within the first year of life. Maternal and infant immunity are interrelated. Immune fitness of the mother is key to sustained health of a child. Vaccination during pregnancy enhances maternal immunity and has a tremendous potential to improve neonatal immunity to pathogens. However, major gaps remain in our understanding of how the immunologically unique setting of pregnancy influences responses to vaccination, the rules of maternal Ab transfer, and the interactions between transferred maternal Ab and the infant immune system. To fill this knowledge gap, we have proposed synergistic and multidisciplinary studies organized in three Aims that will: 1. Distinguish unique features and predictors of vaccine-induced immunity during pregnancy. 2. Define the principles governing maternal antibody transfer. 3. Identify determinants of infant immunity and responses to vaccines. MADI consists of four integrated and synergistic Projects (P) and three Cores (C): P1 will determine the influence of pregnancy on Ab biophysical and functional features and on B/T cell responses to vaccines. P2 will identify Ab-intrinsic factors underlying transfer via placenta and breast milk. P3 will identify features of transferred maternal Ab mediating immunity to pathogens and regulating vaccine responses in infants. P4 will identify cellular and molecular predictors of responses to vaccination in the mother-infant dyad. C1 will provide cutting- edge systems serology and Ab engineering technologies, training, and quality control. C2 will provide centralized management and analysis of data from all projects and will manage data dissemination. The Admin Core will provide management and programmatic support. The MADI team combines complementary expertise, access to unique and well characterized clinical cohorts, and state-of-the-art methods to dissect complex maternal-infant immune interactions. MADI has public health significance and translational value in 1) investigating the immunobiology of maternal immunization at a new breadth and depth; 2) identifying novel actionable targets to improve effectiveness of maternal immunization; 3) informing vaccine design and implementation; and 4) stimulating the field of maternal- infant immunology and vaccinology by generating new analytical tools, mechanistic insights, and rich hypothesis- generating systems immunology datasets. Such knowledge can transform the field of maternal immunization.

总体摘要——母体免疫和婴儿免疫的决定因素 （马迪） 传染病仍然是全球 5 岁以下儿童死亡的主要原因。 新生儿和出生后一年内的婴儿的免疫力是相互关联的。 母亲的健康是怀孕期间疫苗接种可增强母亲健康的关键。 免疫力，在提高新生儿对病原体的免疫力方面具有巨大潜力，但仍存在重大差距。 仍然在我们对怀孕的免疫学独特环境如何影响的理解中 对疫苗接种的反应、母体抗体转移的规则以及转移之间的相互作用 为了填补这一知识空白，我们提出了协同和免疫系统。 以三个目标组织的多学科研究将： 1. 区分妊娠期间疫苗诱导免疫的独特特征和预测因素。 2. 明确母源抗体转移的原则。 3. 确定婴儿免疫力和疫苗反应的决定因素。 MADI由四个综合协同项目（P）和三个核心（C）组成：P1将决定影响力 将确定妊娠对 Ab 生物物理和功能特征以及 B/T 细胞对疫苗反应的影响。 通过胎盘和母乳进行转移的抗体内在因素将识别转移的特征。 母体抗体介导对病原体的免疫并调节婴儿的疫苗反应将被识别。 母婴 C1 对疫苗接种反应的细胞和分子预测因子将提供切割。 边缘系统血清学和抗体工程技术、培训和质量控制将提供集中化。 管理和分析所有项目的数据，并将管理数据传播。 提供管理和计划支持。 MADI 团队结合了互补的专业知识、独特且特征明确的临床经验 队列和最先进的方法来剖析复杂的母婴免疫相互作用。 MADI 在以下方面具有公共卫生意义和转化价值：1) 研究母体免疫生物学 免疫接种达到新的广度和深度；2) 确定新的可操作目标，以提高免疫效果 孕产妇免疫；3) 为疫苗设计和实施提供信息；4) 促进孕产妇免疫领域的发展； 通过产生新的分析工具、机制见解和丰富的假设来研究婴儿免疫学和疫苗学 生成系统免疫学数据集。这些知识可以改变孕产妇免疫领域。