Maternal Antibody Interference and Hybrid Immune Responses to COVID-19 Vaccination in Young Children

Passively transferred SARS-CoV-2 maternal antibody (MatAb) provides significant protection against COVID-19 hospitalization in infancy, however the impact of MatAb presence and prior COVID-19 infection on the immunogenicity and longitudinal durability of SARS-CoV-2 mRNA vaccination in young children, is not known. Here, we evaluate pre- and post-vaccination and longitudinal SARS-CoV-2 antibody responses of 66 young children aged six months to four years of age. We found that young children mount a robust immune response to mRNA SARS-CoV-2 vaccines regardless of prior infection history. In contrast, MatAb presence at the time of vaccination significantly inhibited the induction and long-term durability of vaccine-induced humoral immunity. Post-primary vaccine IgG levels were not significantly different by biological sex or vaccine manufacturer. MatAb interference resolved by twelve months of age; strategic booster dosing or optimized primary series timing may overcome maternal antibody inhibition and optimize immunologic protection in young children.