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 怀孕期间的免疫接种是保护母亲及其婴儿的有效干预措施， 婴儿的常规疫苗接种。破伤风，B。百日咳和季节性流感疫苗的接种对象是 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 通过胎盘和产后通过母乳。然而，孕妇接种的疫苗并没有得到 专为这一特定群体设计，但针对非妊娠健康成人进行测试。深刻 免疫调节发生在妊娠期间，预计这将影响对疫苗的反应。我们 初步数据显示，在孕妇中存在不同的糖基化疫苗特异性血清IgG亚型 在季节性流感疫苗接种后，双半乳糖基化增加，表明非炎症状态。 孕妇产生的抗体在亲合力和功能上也有差异。 MADI项目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细胞对疫苗的应答[破伤风、白喉和无细胞百日咳（TdaP）和流感] 给孕妇和非孕妇对照。提出了三个目标： 目的1 -研究妊娠对疫苗的体液、B和T细胞应答的影响。我们将 确定在抗微生物活性期间Ab糖基化的动态概况以及Fab和Fc介导的抗微生物活性。 应用传统检测方法和创新系统， 我们还将研究疫苗特异性B和T细胞应答的动力学以及它们的免疫应答。 与抗体修饰相关。 目的2 -确定母乳中疫苗诱导抗体的独特特征。抗体聚糖谱和功能 将在Tdap和流感疫苗接种母亲的母乳中进行纵向检查。AB的特点 母乳将与循环中的Ab进行比较。 目的3 -确定疫苗特异性母体Ab的体内属性。机械实验涉及 将进行差异糖基化抗体的小鼠过继转移，以确定 妊娠相关聚糖修饰对抗体寿命和抗体体内保护能力的影响。 这种体液和细胞反应演变的详细表征和对免疫应答的机制性询问， 在怀孕期间和怀孕后没有进行过。了解怀孕对疫苗的影响 这些反应将为有效疫苗的研制提供信息，以改善母亲和儿童的健康。