Placental determinants of neonatal immune function in maternal HIV infection

孕产妇艾滋病毒感染中新生儿免疫功能的胎盘决定因素

• 批准号: 9900843
• 负责人: IRINA BURD
• 金额: $ 21.25万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9900843
• 关键词: Acute; Adaptive Immune System; Address; Affect; Algorithms; Antibodies; BCG Vaccine; Biopsy; Birth; Blood; Blood specimen; CD8-Positive T-Lymphocytes; CD8B1 gene; Caring; Cells; Cellular Immunity; Child; Chronic; Clinical Data; Communicable Diseases; Data; Decidua Basalis; Development; Disease; Enrollment; Exposure to; Fc Receptor; Flow Cytometry; Funding; HIV; HIV Infections; HIV-exposed uninfected infant; Haemophilus influenzae; Health; Humoral Immunities; Immune; Immune response; Immune system; Immunity; Immunologic Markers; Immunologics; Immunology; Impairment; India; Infant; Infant Mortality; Infection; Inflammation; Inflammatory Response Pathway; Intervention; Lead; Life; Longevity; Maternal antibody; Mother-to-child HIV transmission; Mothers; Mus; National Institute of Child Health and Human Development; Neonatal; Newborn Infant; Outcome; Peripheral; Peripheral Blood Mononuclear Cell; Placenta; Play; Population; Postpartum Period; Pregnancy; Pregnant Women; Process; Production; Ramp; Regulatory T-Lymphocyte; Reporting; Risk; Role; Sampling; Schedule; Stains; Stimulus; Stratification; Streptococcus pneumoniae; Technology; Testing; Tuberculosis; Umbilical Cord Blood; United States National Institutes of Health; Vaccines; Viral; Viral Load result; Viremia; Vulnerable Populations; Woman; adaptive immunity; antiretroviral therapy; biobank; cohort; cytokine; design; fetal programming; fetus at risk; healthy pregnancy; immune function; improved; in utero; influenzavirus; neonatal Fc receptor; neonatal immune system; neonate; neuroinflammation; offspring; pathogen; pregnant; prenatal testing; prevent; pup; receptor expression; respiratory; response; screening; vaccine efficacy

ABSTRACT: HIV-exposed but uninfected (HEU) infants are twice as likely to die as HIV-unexposed and uninfected infants (HUU), mainly from other infectious diseases. There is an urgent need to understand how maternal HIV infection–whether controlled or not– impacts the development of the neonatal immune system. With this information, we can develop algorithms to prevent infectious diseases in HEU that account for their functional immune deficits. We hypothesize that maternal HIV infection results in inflammation of the placenta, decreased maternal-to- child transfer of antibodies, and differential programming of the neonatal immune system that impairs the immune response to vaccines. To test this hypothesis, we will integrate clinical data with immunologic data we will obtain from maternal, placenta and neonatal samples that were collected as part of an NIH-funded R01 study we have been conducting in India since 2014. We enrolled a unique, well-defined cohort of maternal- infant pairs with and without HIV and followed them longitudinally through pregnancy and the first year postpartum. We propose to capitalize on these stored samples to address the following aims: Aim 1. Compare the Treg/CD8+ T cell ratio in maternal blood, placenta, and cord blood samples by maternal HIV status and viral load. This aim will establish the relationship between immune cells and cytokines in maternal blood, placenta and cord blood samples, using flow cytometry, immunecard technology and immunohistochemical staining. Understanding how maternal and placental immunology relate to neonatal immune development may help us predict which infants will have impaired immune responses to pathogens. Aim 2. Determine the effect of placental immune function on infants’ humoral and cellular immunity. This aim will (1) identify how HIV decreases the transplacental transfer of antibodies to key respiratory pathogens involved in HEU infant mortality, including S. pneumoniae, H. influenzae, and influenza virus; and (2) determine if placental inflammation impacts the longevity of the infant’s immune response to BCG vaccine. Using these data, we can develop screening tests to predict which neonates will have the greatest immune compromise at birth. Studying the role of the placenta in the development of the neonatal immune system may also reveal key differences between HEU and HUU infants that will allow us to optimize care for this vulnerable population.

摘要：艾滋病毒暴露但未感染的（HEU）婴儿死亡的可能性是艾滋病毒无暴露的两倍，并且 未感染的婴儿（HUU），主要来自其他传染病。迫切需要了解如何 孕产妇的艾滋病毒感染（无论是否受控）会影响新生儿免疫系统的发展。 有了这些信息，我们可以开发算法以防止HEU中的传染病 功能免疫缺陷。 我们假设生物HIV感染会导致斑点感染，降低了母乳至 抗体的儿童转移和新生儿免疫系统的差异编程 对疫苗的免疫反应。为了检验这一假设，我们将将临床数据与免疫学数据整合在一起 将从Mater，Pleceta和Neonatal样品中获得，这些样本是作为NIH资助R01的一部分收集的 自2014年以来，我们一直在印度进行的研究。我们招募了一个独特的，定义明确的母体群体 婴儿对带有和没有艾滋病毒的配对，并在怀孕期间纵向跟随它们 产后。我们建议利用这些存储的样本来解决以下目的： AIM 1。比较遗物血液，胎盘和脐带血样本中Treg/CD8+ T细胞的比例 孕产妇的艾滋病毒状况和病毒负荷。这个目标将确定免疫细胞与 使用流式细胞术，immunecard技术，母血，胎盘和脐带血样本中的细胞因子 和免疫组织化学染色。了解母乳和占地免疫学与新生儿的关系 免疫发育可能有助于我们预测哪些婴儿对病原体的免疫反应受损。 AIM 2。确定位置免疫功能对婴儿的体液和细胞的影响 免疫。该目标将（1）确定HIV如何减少抗体向密钥的移植转移 参与HEU婴儿死亡率的呼吸道病原体，包括肺炎链球菌，H。Attractzae和actractza 病毒; （2）确定位置炎症是否影响婴儿免疫反应的寿命 BCG疫苗。 使用这些数据，我们可以开发筛选测试，以预测哪些新生儿将具有最大的免疫力 出生时妥协。研究plapeta在新生儿免疫系统发展中的作用可能 还揭示了HEU和HUU婴儿之间的关键差异，这将使我们能够优化对此脆弱的护理 人口。