Breast Milk–Derived Antibodies Impair Vaccine Immunity in Suckling Mice

Abstract Breast milk confers multiple benefits to the neonate, including passive immunity against multiple microorganisms via Abs. However, it remains unclear whether breast milk–derived Abs affect vaccine-induced immunity in the neonate. We evaluated in C57BL/6 and BALB/c mice whether breastfeeding from an mRNA-SARS-CoV-2–vaccinated dam affects vaccine-induced immunity in neonate mice. Using an experimental model that allows the distinction of maternal Abs and neonate Abs based on their allotype, we show that breastfeeding from an immune dam is associated with reduced vaccine immunity in the neonate. Importantly, mice that breastfed from an immune dam showed reduced numbers of plasma cells after vaccination, relative to mice that breastfed from a naive dam. Our subsequent studies using an mRNA-luciferase reporter system show that passive transfer of Abs through breastfeeding accelerates the clearance of vaccine Ag in suckling mice, resulting in reduced Ag availability. Altogether, maternal Abs transferred through breast milk can protect against infectious microorganisms, but they may also interfere with the neonate’s response to vaccination by accelerating the clearance of vaccine Ag. These findings are important for understanding the effects of maternal Abs on the neonate’s response to vaccines and may provide insights for improving neonatal vaccines.