Infant Protection from Influenza through Maternal Influenza Immunization

项目总结/摘要 流感每年影响全球1500多万婴儿，导致约40万例重症病例 每年有一万人死亡孕妇在怀孕期间接种流感疫苗（MII）可保护婴儿免受 这为降低发病率和死亡率提供了巨大的机会。保护措施通过三个 机制：减少婴儿接触母体感染、经胎盘疫苗特异性抗体（Ab）， 可能还有母乳疫苗特异性抗体然而，在我们对信息产业的理解方面存在着严重的差距， 免疫的最佳时机，婴儿抗体保护的定义相关性，以及疫苗抗体的重要性 在母乳中。本研究的总体目标是通过调查 通过免疫接种为婴儿提供流行病学和免疫保护， 怀孕，重点是母乳介导的保护。利用49，000名母亲的回顾性队列- 匹兹堡大学医学中心（UPMC）的婴儿对，目标1a将检查个人， 婴儿暴露于MII和母乳与婴儿流感风险之间的联合关联，以确定 如果MII和母乳的组合导致对流感的协同保护。Aim 1B将使用此功能 队列，以确定妊娠期间MII的时间是否影响婴儿流感的可能性 发生，同时控制母乳的消耗。目标2将使用婴儿流感病例/对照 测定血清（目标2a）和母乳（目标2b）中流感疫苗特异性Ab滴度的研究设计 与预防流感相关的疾病。病例和对照将在大约440例 将从UPMC的新疫苗监测网络（NVSN）研究中招募的母婴对 在连续四个流感季节收集标本。NVSN是一个疾病控制中心， 儿童急性呼吸道疾病与无症状对照的预防研究。完成这些 目的将大大提高我们对通过产妇保护婴儿的理解。 流感免疫接种，并大大扩大我们对母乳中疫苗抗体的了解， 这是今后采取干预措施保护这一弱势群体的一个阶段。在导师的指导下， 强大的机构支持，PI还将获得必要的强化指导，教学教育， 研究经验，成为一个独立的调查员，支持职业发展目标， 先进的定量方法，团队科学的领导能力，人类受试者研究的实践经验 以及传染病和免疫学的实验室培训。这项工作将提供必要的初步数据 支持今后的赠款申请，继续侧重于通过产妇疫苗保护婴儿。与 这些新技术和新的初步数据，PI将准备领导大规模的母婴疫苗研究 研究，最终改善母婴健康，并进一步NIAID的使命，以了解，治疗和 预防传染病。

PROJECT SUMMARY/ABSTRACT Influenza affects over 15 million infants each year worldwide resulting in approximately 400,000 severe cases and 10,000 deaths annually. Maternal influenza immunization (MII) during pregnancy protects infants against disease, presenting tremendous opportunity to reduce morbidity and mortality. Protection occurs through three mechanisms: decreased infant exposure to maternal infections, transplacental vaccine-specific antibody (Ab), and possibly breastmilk vaccine-specific Ab. Yet, there are critical gaps in our understanding of MII including optimal timing of immunization, defined correlates of Ab protection in infants, and the importance of vaccine Ab in breastmilk. The overarching goal of this research is to address these gaps by investigating the epidemiologic and immunologic protection provided to infants against influenza through immunization during pregnancy with a focus on breastmilk-mediated protection. Utilizing a retrospective cohort of 49,000 mother- infant pairs at University of Pittsburgh Medical Center (UPMC), Aim 1a will examine the individual and combined associations between infant exposure to MII and breastmilk and risk of infant influenza to determine if the combination of MII and breastmilk results in synergistic protection against influenza. Aim 1b will use this cohort to determine whether the timing of MII during pregnancy affects the likelihood of infant influenza occurrence, while controlling for consumption of breastmilk. Aim 2 will use an infant influenza case/control study design to determine the influenza-vaccine specific Ab titer in serum (Aim 2a) and breastmilk (Aim 2b) that correlates with protection against influenza. Cases and controls will be identified among approximately 440 mother-infant pairs who will be recruited from the New Vaccine Surveillance Network (NVSN) study at UPMC over four consecutive influenza seasons with specimens collected. NVSN is a Center for Disease Control and Prevention study of children with acute respiratory illness and asymptomatic controls. Accomplishment of these aims will significantly improve our understanding of the protection provided to infants through maternal influenza immunization and significantly expand our understanding of vaccine-Ab in breastmilk, setting the stage for future interventions to protect this vulnerable population. With guidance from committed mentors and strong institutional support, the PI will also receive the necessary intensive mentorship, didactic education, and research experience to become an independent investigator, supporting career development objectives in advanced quantitative methods, leadership in team science, hands-on experience in human subjects’ research and laboratory training in infectious diseases and immunology. This work will provide essential preliminary data to support future grant applications with a continued focus in infant protection through maternal vaccines. With these new skills and novel preliminary data, the PI will be poised to lead large studies maternal-infant vaccine research, ultimately improving maternal-infant health and furthering NIAID’s mission to understand, treat and prevent infectious diseases.