The interplay of maternal antibody and newborn vaccine responses

Young infants are at high risk for severe disease following influenza virus infection. The current strategy for protecting infants is to increase antibody in the mother that can be transferred across the placenta to the fetus such that infants are born with influenza virus-specific antibodies on board. However, while maternal antibodies can decrease the likelihood that infants develop influenza disease, in many cases this protection is incomplete and infants remain at high risk. Further, maternal antibody will wane in all infants, leaving them more susceptible to infection. The combination of the lack of a vaccine for infants under the age of 6 months, the need for two doses of vaccine to achieve protective levels of antibody, and waning maternal antibody results in a window of vulnerability in infants. Our goal is to effectively vaccinate young infants when maternal antibody is at high levels, such that as maternal antibody is waning, a protective anti-influenza response is rising in the infant. Among the challenges associated with effective vaccination of newborns is the potential for interference by maternal antibody. Currently, there is debate in the field regarding the extent of the impediment posed by maternal antibody in the context of influenza vaccination. A fuller understanding of the potential for maternal antibody-mediated regulation has been hampered by the lack of study using a model that closely resembles humans in maternal antibody transfer and infant immune system development/function. Here, we use the nonhuman primate model to investigate this significant area. NHP are the most reflective pre-clinical model of human maternal antibody transfer and infant immune development/function. Vaccine responses in infants born to influenza virus-immune or naive mothers will be evaluated at the antibody and cellular level. These studies will significantly move forward our mechanistic understanding of the impact of maternal antibody in the context of influenza vaccination and provide insights into the development of more effective vaccines for newborns. Project Number: 1R01AI189601-01 | Fiscal Year: 2025 | NIH Institute/Center: National Institute of Allergy and Infectious Diseases (NIAID) | Principal Investigator: Martha Alexander-Miller | Institution: WAKE FOREST UNIVERSITY HEALTH SCIENCES, WINSTON-SALEM, NC | Award Amount: $793,102 | Activity Code: R01 | Study Section: Vaccines Against Infectious Diseases Study Section[VID] View on NIH RePORTER: https://reporter.nih.gov/project-details/1R01AI18960101