Breast milk antibody Fc features linked to HIV transmission during breastfeeding

Breastfeeding shapes early immunity, but without antiretroviral therapy (ART), carries a risk of HIV transmission. The role of breast milk antibodies in this process remains unclear. Using systems serology, we profiled milk antibodies from transmitting and non-transmitting mothers in the Zambia Exclusive Breastfeeding Study. Transmission was linked to higher gp41-specific IgG1 and increased effector functions, likely driven by elevated milk viral loads. In contrast, non-transmitting mothers showed p24-specific antibody responses associated with lower viral loads, suggesting better viral control. Fc glycosylation analysis revealed higher digalactosylated IgG in transmitting mothers, linked to enhanced inflammatory responses. Overall, these findings highlight distinct antibody signatures associated with HIV transmission risk or protection and provide insights for vaccine and antibody-based prevention strategies.