Maternal Immunity

项目1--摘要 孕期免疫是保护母婴安全的有效干预措施。 到婴儿的常规疫苗接种。破伤风、百日咳和季节性流感疫苗接种给 孕妇和后代受益于疫苗诱导的抗体，这些抗体在怀孕期间传播 通过胎盘和产后通过母乳。然而，给孕妇接种的疫苗并没有 专为这一特定群体设计，但目标是非怀孕的健康成年人并在其中进行测试。一种深刻的 免疫调节发生在怀孕期间，这预计会影响对疫苗的反应。我们的 初步数据显示孕妇糖基化疫苗特异性血清免疫球蛋白亚型不同 在季节性流感疫苗接种后，双半乳糖化增加表明非炎症状态。 孕妇产生的抗体在亲和力和功能上也存在差异。 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细胞对疫苗的反应[破伤风、白喉和无细胞百日咳(Tdap)和流感] 给怀孕妇女和非怀孕妇女使用。建议的三个目标是： 目的1-探讨妊娠对体液、B和T细胞对疫苗免疫应答的影响。我们会 测定抗体糖基化的动态变化以及Fab和Fc介导的抗微生物活性 孕期和产后最多6个月应用传统检测方法和创新系统 血清学平台我们还将询问疫苗特异性B和T细胞反应的动力学以及它们的 与抗体修饰有关。 目的2-鉴定母乳中疫苗诱导的抗体的明显特征。抗体葡聚糖谱及其功能 将在TDAP和接种流感疫苗的母亲的母乳中进行纵向检查。《红楼梦》中单抗的特点 将母乳与循环中的抗体进行比较。 目的3-确定疫苗特异性母体抗体的体内属性。机械实验涉及到 将进行差异糖基化抗体的小鼠过继转移以确定 妊娠相关多糖修饰对抗体寿命和体内抗体保护能力的影响。 体液和细胞反应演变的如此详细的特征以及对 怀孕期间和怀孕后的功能尚未进行。了解怀孕对疫苗的影响 应对措施将为有效疫苗的开发提供信息，以改善母婴健康。

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.