Protection of at-risk low birth weight infants against influenza via maternal antibody

通过母源抗体保护高危低出生体重婴儿免受流感侵害

• 批准号: 10374134
• 负责人: Alisa Kachikis
• 金额: $ 18.85万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10374134
• 关键词: 2019-nCoV; Acute respiratory infection; Affect; Antibodies; Antibody titer measurement; Antigens; Biophysics; COVID-19 vaccine; Chorionic villi; Clinical; Clinical Trials; Cohort Studies; Communicable Diseases; Computational Biology; Computer Analysis; Development; Discipline of obstetrics; Effector Cell; Enzyme-Linked Immunosorbent Assay; Fc Receptor; Fetus; Gestational Age; Goals; Gold; High-Risk Pregnancy; Immune; Immunity; Immunization Programs; Immunoglobulin G; Immunohistochemistry; Immunology; Impairment; Incidence; Infant; Infection; Infection prevention; Inflammatory; Influenza; Knowledge; Low Birth Weight Infant; Lytic; Maternal antibody; Mentorship; Methods; Modeling; Mothers; Nature; Neonatal; Neonatal Mortality; Pathology; Perinatal mortality demographics; Physicians; Placenta; Placental Insufficiency; Plasma; Population; Pregnancy; Pregnant Women; Prevention strategy; Process; Research; Research Personnel; Research Training; Resource-limited setting; Respiratory Disease; Respiratory Tract Infections; Risk; Sampling; Scientist; Serology; Shapes; Small for Gestational Age Infant; Statistical Data Interpretation; Syncytiotrophoblast; System; Testing; Training; Training Programs; Umbilical Cord Blood; Vaccinated; Vaccination; Vaccines; Woman; antibody test; antibody transfer; biophysical properties; burden of illness; career; cohort; fetal; global health; high risk; high risk population; immune function; improved; influenza virus vaccine; innovation; insight; maternal vaccination; mortality; neonatal Fc receptor; neonatal immune system; neonatal immunity; neonatal infection; neonate; novel; novel strategies; novel vaccines; pathogen; placental morphology; premature; programs; prospective; receptor expression; respiratory; respiratory pathogen; respiratory virus; skills; statistics; success; translational research program; vaccination strategy; vaccine delivery; vaccinology; virology

PROJECT SUMMARY / ABSTRACT Acute respiratory infections are the leading cause of mortality among neonates globally, particularly among low birthweight infants from pregnancies complicated by prematurity or placental insufficiency. Maternal immuniza- tion, the vaccination of pregnant women to enhance antibody transported across the placenta to the fetus, is utilized increasingly as an infection prevention strategy to protect neonates from pathogens such as influenza, and may be critical as new vaccines against SARS-CoV-2 are developed. This proposal aims to better eluci- date transplacental antibody transfer in low- and high-risk pregnancies, specifically those with prematurity or placental insufficiency, which is not known. It also describes a research training program that will allow me to become an independent physician-scientist with a translational research program focusing on infectious diseases and vaccines in pregnancy. This proposal builds upon my training in high-risk obstetrics and global health, and provides a detailed plan to improve my knowledge of virology, immunology, vaccinology, cohort studies and statistical analysis. It incorporates the expertise of an outstanding mentorship team, including experts in infectious diseases, immunology, pathology, statistics, and computational biology who are dedicated to the success of this project and the development of my career as an independent clinical researcher. The first aim of this proposal involves establishing normal and high-risk pregnancy cohorts and quantifying transplacental antibody transfer in the context of pregnancies resulting in both normal and low birth weight infants, including those complicated by placental insufficiency leading to small for gestational age infants or prematurity. I will compare quantity of transplacental antibody transfer of total IgG, influenza- and SARS-CoV- 2- specific antibodies, and expression of neonatal Fc receptor in placentas. I will also compare neonatal immunity against influenza among women who did and did not receive influenza vaccine during pregnancy, allowing the opportunity to develop multivariable models and adjust for multiple clinical covariates. For my second aim, I will characterize antibody profiles and transplacental transfer in the same cohorts using a systems serology approach to determine biophysical and effector functions of maternal and fetal immunology. Through accomplishing the aims in this proposal, I will contribute significantly to our knowledge of maternal immunizations, maternal and neonatal immune interactions and neonatal immunity against influenza and SARS-CoV-2. Improved understanding and characterization of transplacental antibody transfer in the context of maternal immunizations may provide insight in the optimization and individualization of vaccine delivery and timing in high-risk pregnancies and, ultimately, has the potential to improve neonatal survival globally. This proposal will allow me to develop a unique set of cross-disciplinary skills and expertise in order to transition to independence as a physician scientist with a larger research program specializing in respiratory infectious diseases and vaccines within the context of low- and high-risk pregnancies.

项目概要/摘要 急性呼吸道感染是全球新生儿死亡的主要原因，尤其是低收入新生儿 因妊娠并发早产或胎盘功能不全而出生体重的婴儿。母体免疫接种 孕妇接种疫苗可以增强抗体通过胎盘输送给胎儿的能力 越来越多地用作感染预防策略，以保护新生儿免受流感等病原体的侵害， 随着针对 SARS-CoV-2 的新疫苗的开发，这可能至关重要。该提案旨在更好地阐明 确定低风险和高风险妊娠中经胎盘抗体转移的日期，特别是早产或早产的妊娠 胎盘功能不全，目前尚不清楚。它还描述了一个研究培训计划，使我能够 成为一名独立的医师科学家，拥有专注于传染病的转化研究项目 怀孕期间的疾病和疫苗。该提案建立在我在高风险产科和全球的培训基础上 健康，并提供了详细的计划来提高我对病毒学、免疫学、疫苗学、队列的了解 研究和统计分析。它融合了杰出导师团队的专业知识，包括 传染病、免疫学、病理学、统计学和计算生物学领域的专家 为了这个项目的成功和我作为一名独立临床研究员的职业发展。 该提案的第一个目标是建立正常和高风险妊娠队列并量化 怀孕期间经胎盘抗体转移导致正常和低出生体重 婴儿，包括因胎盘功能不全而导致小于胎龄婴儿的婴儿或 早熟。我将比较总 IgG、流感病毒和 SARS-CoV- 的胎盘抗体转移量 2-特异性抗体，以及胎盘中新生儿Fc受体的表达。我也会比较新生儿 怀孕期间接种和未接种流感疫苗的妇女对流感的免疫力， 允许有机会开发多变量模型并针对多个临床协变量进行调整。为了我的 第二个目标，我将使用 系统血清学方法确定母体和胎儿免疫学的生物物理和效应功能。 通过实现本提案中的目标，我将为我们对孕产妇的了解做出重大贡献 免疫接种、孕产妇和新生儿免疫相互作用以及新生儿对流感和流感的免疫力 SARS-CoV-2。提高对经胎盘抗体转移的理解和表征 孕产妇免疫接种的研究可以为疫苗接种的优化和个体化提供见解 并最终有可能提高全球新生儿的生存率。这 该提案将使我能够发展一套独特的跨学科技能和专业知识，以便过渡到 独立作为一名医师科学家，拥有更大的呼吸道传染病研究项目 低风险和高风险妊娠背景下的疾病和疫苗。