Maternal Immunity

母体免疫力

• 批准号: 10616548
• 负责人: Marcela F Pasetti
• 金额: $ 98.68万
• 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/10616548
• 关键词: Activities of Daily Living; Adoptive Transfer; Adult; Affect; Antibodies; Antibody Response; Antigens; Avidity; B-Lymphocytes; Binding; Biological Assay; Biological Process; Biophysics; Bordetella pertussis; Cell Compartmentation; Child; Circulation; Clinical; Cohort Analysis; Data; Development; Dimensions; Diphtheria; Diphtheria-Tetanus-acellular Pertussis Vaccines; Event; Evolution; Exhibits; Future; Half-Life; Human; Human Milk; Humoral Immunities; Immune response; Immunity; Immunization; Immunoglobulin G; Infant; Infection prevention; Infectious Agent; Influenza; Influenza vaccination; Kinetics; Knowledge; Life; Longevity; Maternal antibody; Maternally-Acquired Immunity; Measurement; Mediating; Modification; Molecular; Mothers; Mus; Neonatal; Pertussis; Placenta; Polysaccharides; Population; Postpartum Period; Pregnancy; Pregnant Women; Production; Property; Recommendation; Reporting; Serology; Serum; Specimen; System; Systems Analysis; T cell response; T-Lymphocyte; Testing; Tetanus; Vaccinated; Vaccination; Vaccine Design; Vaccines; Woman; antibody transfer; antimicrobial; biophysical properties; cohort; design; effective intervention; experimental study; glycosylation; health of the mother; immunoregulation; improved; in vivo; influenza virus vaccine; innovation; maternal vaccination; offspring; post pregnancy; postnatal; pregnant; prevent; response; seasonal influenza; synergism; vaccination strategy; vaccine response; vaccine-induced antibodies; vaccine-induced immunity

PROJECT 1 – ABSTRACT Immunization during pregnancy is an effective intervention for protection of both mothers and their infants prior to infant’s routine vaccination. Tetanus, B. pertussis and seasonal influenza vaccines are administered to pregnant women and offspring benefit from vaccine-induced antibodies which are transferred during gestation via placenta and postnatally via breast milk. Vaccines given to pregnant women, however, have not been designed for this specific group, but are targeted for and tested in the non-pregnant healthy adults. A profound immune modulation takes place during gestation, which is expected to influence responses to vaccines. Our preliminary data revealed differentially glycosylated vaccine-specific serum IgG subtypes in pregnant women following seasonal flu vaccination with an increase in di-galactosylation indicative of non-inflammatory state. Antibodies produced by pregnant women also diverged in avidity and function. MADI Project 1 will investigate biophysical and functional features of humoral immunity as well antigen-specific B and T cell responses to vaccines [Tetanus, Diphtheria and acellular Pertussis (TdaP) and influenza] administered to pregnant women and non-pregnant controls. Three aims are proposed to: Aim 1 – Investigate the impact of pregnancy on humoral, B and T cell responses to vaccines. We will determine the dynamic profile of Ab glycosylation, and Fab- and Fc-mediated anti-microbial activity during pregnancy and up to 6 months post-delivery applying traditional assays as well as the innovative systems serology platform We will also interrogate kinetics of vaccine-specific B and T cell responses and their association with antibody modifications. Aim 2 – Identify distinct features of vaccine-induced Ab in breast milk. Antibody glycan profile and function will be examined longitudinally in breast milk from Tdap and influenza-vaccinated mothers. Features of Ab in breast milk will be compared with those of with Ab in circulation. Aim 3 – Determine in vivo attributes of vaccine-specific maternal Ab. Mechanistic experiments involving mouse adoptive transfer of differentially glycosylated antibodies will be conducted to ascertain the impact of pregnancy-associated glycan modifications on antibody longevity and protective capacity of antibodies in vivo. Such detailed characterization of humoral and cellular response evolution and mechanistic interrogation of function during and after pregnancy has not been conducted. Understanding the impact of pregnancy on vaccine responses will inform the development of effective vaccines to improve the health of mother and child.

项目1 - 摘要 怀孕期间的免疫是对母亲及其婴儿的有效干预措施 婴儿的常规疫苗。破伤风，百日咳和季节性影响被给予 孕妇和后代受益于疫苗诱导的抗体，这些抗体在妊娠期间转移 通过斑点和产后通过母乳。但是，给孕妇的疫苗还没有 专为该特定组设计，但针对并在非妊娠健康成年人中进行了测试。深刻 免疫调节发生在妊娠期间，这预计会影响对疫苗的反应。我们的 初步数据显示，孕妇的差异糖基化疫苗特异性血清IgG亚型 在季节性流感疫苗之后，二半乳糖基化增加了非炎症状态。 孕妇产生的抗体在亲和力和功能方面也有所不同。 MADI Project 1将研究体液免疫的生物物理和功能特征以及抗原特异性 B和T细胞对疫苗的反应[TETANIUS，白喉和细胞百日咳（TDAP）和影响力] 给予孕妇和非怀孕的对照。提出了三个目标： AIM 1 - 研究妊娠对疫苗的体液，B和T细胞反应的影响。我们将 确定AB糖基化的动态曲线，以及FC和FC介导的抗微生物活性 怀孕和运送后长达6个月，应用传统测定法以及创新系统 血清学平台我们还将询问疫苗特异性B和T细胞反应的动力学及其 与抗体修饰有关。 AIM 2 - 确定母乳中疫苗诱导的AB的不同特征。抗体聚糖曲线和功能 将在TDAP的母乳中纵向检查，并影响为疫苗接种的母亲。 AB的功能 母乳将与循环中AB的母乳进行比较。 AIM 3 - 确定疫苗特异性材料AB的体内属性。机械实验涉及 将进行小鼠自适应转移不同的糖基化抗体，以确定 妊娠相关的聚糖修饰对抗体寿命和体内抗体的受保护能力。 对体液和细胞反应进化的详细表征以及机械询问 尚未进行怀孕期间和之后的功能。了解怀孕对疫苗的影响 回应将为开发有效的疫苗开发，以改善母子的健康状况。