COVID-19 mRNA vaccines drive differential Fc-functional profiles in pregnant, lactating, and non-pregnant women

Substantial immunological changes occur throughout pregnancy to promote tolerization of the mother to the fetus and allow fetal growth. However, additional local and systemic immunological adaptations also occur, allowing the maternal immune system to continue to protect the dyad against pathogens both during pregnancy and after birth through lactation. This fine balance of tolerance and immunity, along with physiological and hormonal changes, contribute to increased susceptibility to particular infections in pregnancy, including more severe coronavirus disease 2019 (COVID-19). Whether these changes also make pregnant women less responsive to vaccination or induce altered immune responses to vaccination remains incompletely understood. To holistically define potential changes in vaccine response during pregnancy and lactation, we deeply profiled the humoral vaccine response in a group of pregnant and lactating women and non-pregnant age-matched controls. Vaccine-specific titers were comparable between pregnant women, lactating women, and non-pregnant controls. However, Fc receptor (FcR)-binding and antibody effector functions were induced with delayed kinetics in both pregnant and lactating women compared to non-pregnant women after the first vaccine dose, which normalized after the second dose. Antibody boosting resulted in high FcR-binding titers in breastmilk. These data suggest that pregnancy promotes resistance to generating highly inflammatory antibodies and indicates that there is a critical need to follow prime-boost timelines in this vulnerable population to ensure full immunity is attained.