Kready, K. | bioRxiv Science

bioRxiv2026

The transition to postpartum lactation establishes a state of maternal antiviral resilience

Influenza A virus (IAV) causes severe disease during late pregnancy, yet how maternal adaptations in host defense shape susceptibility following childbirth remains unknown. Here, we show that the postpartum period represents a state of enhanced maternal antiviral immunity. Across postpartum stages, dams infected before weaning exhibited increased survival and reduced disease following lethal IAV challenge compared with nonpregnant females. Postpartum protection was associated with enhanced viral clearance and increased pulmonary antigen-specific CD8+ T cells and IL-17A-producing gamma-delta T cells. We identify the transition into lactation as a critical determinant of this protection. Protection extended to highly pathogenic avian influenza. Together, these findings reveal that maternal antiviral immunity remains actively shaped after childbirth, establishing the postpartum lactational period as a distinct state of maternal antiviral resilience.

immunology↗

bioRxiv2023

A long-acting prolactin to combat lactation insufficiency

Human infants are born to breastfeed. While 50% of lactating persons struggle to make enough milk, there are no governmentally-approved drugs to enhance lactation1. Here, we engineer a variant of the naturally-occurring driver of lactation, the hormone Prolactin, to increase its serum half-life and produce a viable drug candidate. Our engineered variant, Prolactin-eXtra Long-acting (Prolactin-XL), is comprised of endogenously active human prolactin fused to an engineered human IgG Fc domain designed to overcome the unique drug development challenges specific to the lactating person-infant dyad. Our Prolactin-XL has a serum half-life of 70.9h in mice, 2,625-fold longer than endogenously active prolactin alone (70.9h v. 0.027h). We demonstrate that Prolactin-XL increases milk production and restores growth of pups fed by dams with pharmacologically-ablated lactation. We show that Prolactin-XL-enhanced lactation is accompanied by reversible, lactocyte-driven changes in mammary gland morphology. This work establishes long-acting prolactins as a potentially powerful pharmacologic means to combat insufficient lactation.

synthetic biology↗