Project Details

Maternal Interference of Infant SARS-CoV-2 mRNA Vaccination

Caitlin Williams, PhD

Summary

BACKGROUND: In 2020 infants accounted for 18% of child COVID-19 hospitalizations, in 2021 children less than 4 years old accounted for 27% of PICU COVID-19 cases and child hospitalizations have increased by 10-fold. Thus, there is a need for infant SARS-CoV-2 vaccination to prevent severe COVID-19 disease in young infants. GAP: Clinical trials for SARS-CoV-2 vaccines did not explicitly include pregnant and nursing women, resulting in a lack of detailed longitudinal immunogenicity and subsequent transfer of antibody. The potential for protective efficacy or maternal interference in infant COVID-19 immunization is understudied and not well understood. HYPOTHESIS: mRNA vaccine elicited anti-SARS-CoV-2 maternal antibodies (matAbs) in humans and mice will strongly bind to the Spike protein of SARS-CoV-2 and to WHO defined variants of concern but will not interfere with infant vaccine-elicited immunity. METHODS: Women recruited through the COVID Vaccination in Pregnant and Breastfeeding Women (COVER) Cohort will provide longitudinal milk samples as well as blood to determine the fluctuations in binding breadth and intensity throughout their COVID-19 immunization schedule as well as in the perinatal period. Balb/c mice will be used to study potential infant responses to immunization within the context of exposure to matAb through the placenta and milk. RESULTS: We found that SARS-CoV-2 mRNA LNP vaccines elicited broadly binding IgG in the serum and breastmilk of post-partum women. Participants with a history of SARS-CoV-2 infection demonstrated enhanced IgG breadth and neutralization in both serum and breastmilk. IMPACT: Characterization of SARS-CoV-2 mRNA vaccine-elicited matAbs that will be transferred to neonates and an accompanying murine model of matAb interference will aid in understanding the composition and function of matAb that neonates are exposed to and their potential to interfere with infant SARS-CoV-2 immunization. This work will help in determining a vaccine schedule compatible with successful infant SARS-CoV-2 mRNA immunization.