Infant Protection from Influenza through Maternal Influenza Immunization

项目总结/文摘

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.