Maternal transfer of mRNA LNP-derived, pathogen-specific, monoclonal IgG to suckling mice

Abstract

Breast milk provides a rich source of naturally derived maternal antibodies that confer passive immunity to infants, protecting them from a variety of respiratory and enteric infections. For at-risk newborns in low- and middle-income countries, supplementing breast milk with pathogen-specific neutralizing and bactericidal antibodies could offer significant short- and long-term health benefits. In this study, we explored the use of mRNA and lipid nanoparticle (LNP) technology to deliver a Vibrio cholerae-specific monoclonal IgG antibody ("ZAC-3") into the milk of lactating mice. Swiss Webster mice were intravenously administered ZAC-3 IgG mRNA-LNPs, and we monitored serum and breast milk for the presence of V. cholerae-specific human IgG1. A single injection of mRNA-LNPs led to rapid and sustained expression of ZAC-3 IgG in both the blood and breast milk of lactating dams. ZAC-3 IgG1 in these samples recognized whole V. cholerae cells by ELISA and exhibited potent vibriocidal activity in the presence of human complement. Furthermore, ZAC-3 IgG was detected in the sera of suckling pups at levels proportional to those in the mothers, demonstrating successful transfer of functional antibodies to the newborns. In conclusion, our findings highlight the potential of mRNA-based monoclonal antibody platforms in the maternal-newborn context and address key challenges associated with the direct delivery of recombinant antibodies.