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.
Acute respiratory infections are among the leading causes of neonatal mortality worldwide with low birth weight infants particularly susceptible and at risk for perinatal mortality. Maternal immunizations are increasingly being used as an infection prevention strategy to protect neonates and infants from respiratory pathogens, yet maternal immunization and transplacental antibody transfer are incompletely understood in pregnancies complicated by prematurity or placental insufficiency leading to small for gestational age infants. This proposal aims to quantify and characterize transplacental antibody transfer and maternal and neonatal immune interactions in these high-risk pregnancies in order to optimize neonatal immunity against respiratory pathogens such as influenza and SARS-CoV-2 in at-risk low birth weight infants.
