Placental Transfer of Maternal Vaccine-Induced Antibodies Differentially Shapes Fc Receptor Engagement, Antibody Function, and Infant Immunity.

Abstract

Maternal vaccination protects mothers directly and infants indirectly through placental transfer of vaccine-induced antibodies. Using multidimensional systems serology across matched maternal, cord blood, and two-month infant samples, we evaluated virus-specific antibody isotypes and functions following maternal influenza and RSV vaccination. The predominant subclass transferred and maintained in infants against H1N1 hemagglutinin (H1) and RSV prefusion (Pre)F was IgG1. Transferred RSV PreF- and H1-specific antibodies exhibited increased neutralization, Fcγ receptor-binding, antibody-dependent complement deposition, and cellular phagocytosis compared with non-transferred maternal antibodies. Although total antibody-dependent neutrophil phagocytosis (ADNP) was comparable between maternal and cord blood for RSV PreF antibodies, RSV PreF, but not H1-specific, FcγRIII-binding antibodies associated with neutrophil phagocytic activity were selectively transferred. Predictive modeling identified distinct correlates of antigen-specific antibody persistence, with maternal and cord blood estradiol emerging as a shared contributor to higher infant IgG1 through two months of age, suggesting estrogenic potentiation of antibody responses in early life.