Infant Protection from Influenza through Maternal Influenza Immunization

项目摘要/摘要 流感每年影响全球1500多万名婴儿，导致约40万例重症病例 每年有1万人死亡。孕妇在孕期接种流感疫苗(MII)可保护婴儿免受 这为减少发病率和死亡率提供了巨大的机会。保护通过三个途径进行 机制：减少婴儿接触孕产妇感染、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，我们对信息产业部的理解存在严重差距，包括 最佳免疫时机，婴儿抗体保护的明确相关因素，以及疫苗抗体的重要性 在母乳里。这项研究的首要目标是通过调查 通过免疫接种为婴儿提供预防流感的流行病学和免疫保护 怀孕，重点是母乳中介的保护。利用49,000名母亲的回溯性队列- 匹兹堡大学医学中心(UPMC)的婴儿配对，Aim 1a将检查个体和 婴儿接触MII和母乳与婴儿流感风险的联合关联以确定 如果婴儿免疫缺陷病毒和母乳的结合能产生协同预防流感的效果。目标1b将使用这一点 确定孕期感染MiI是否会影响婴儿患流感可能性的队列研究 发生，同时控制母乳的摄入量。目标2将使用婴儿流感病例/对照 检测血清(目标2a)和母乳(目标2b)流感疫苗特异性抗体效价的研究设计 这与预防流感有关。将在大约440个病例中确定病例和控制措施 将从UPMC新疫苗监测网络(NVSN)研究中招募的母婴对 连续四个流感季节收集样本。NVSN是疾病控制和研究中心 儿童急性呼吸道疾病的预防研究及无症状对照。实现这些目标 AIMS将显著提高我们对通过母体提供给婴儿的保护的理解 流感疫苗接种，大大扩大了我们对母乳中抗体疫苗的了解，为 为今后采取干预措施保护这一弱势群体做好准备。在忠诚的导师和 在强有力的机构支持下，该协会还将接受必要的强化指导、教育和 研究经验成为一名独立的调查员，支持职业发展目标 先进的定量方法，在团队科学方面的领导地位，在人类受试者研究方面的实践经验 以及传染病和免疫学方面的实验室培训。这项工作将提供必要的初步数据 支持未来的赠款申请，继续把重点放在通过孕产妇疫苗保护婴儿方面。使用 这些新的技术和新颖的初步数据，PI将准备领导大型母婴疫苗研究 研究，最终改善母婴健康，促进NIAID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.