Breast milk delivery of an engineered dimeric IgA protects neonates against rotavirus

• DOI: 10.1016/j.mucimm.2025.01.002
• Publication Date: 2025-01-20T07:34:38Z
• Authors: Stephanie N. Langel; Claire E. Otero; Justin T. Steppe; Caitlin A. Williams; Tatiana Travieso; Jerry Chang; Helen Webster; Lauren E. Williamson; James E. Crowe; Harry B. Greenberg; Huali Wu; Christoph P. Hornik; Katayoun Mansouri; Robert J. Edwards; Victoria Stalls; Priyamvada Acharya; Maria Blasi; Sallie R. Permar
• Keywords: Immunoglobulin A

Dimeric IgA (dIgA) is the dominant antibody in many mucosal tissues. It actively transported onto surfaces as secretory (sIgA) which plays an integral role protection against enteric pathogens, particularly young children. Therapeutic strategies that deliver engineered, potently neutralizing antibodies directly into infant intestine through breast milk could provide enhanced antimicrobial for neonates. Here, we developed a murine model of maternal protective transfer human rotavirus (RV) using systemic administration dimeric monoclonal (mAb). First, showed systemically administered dIgA passively transferred and stomach suckling pups dose-dependent manner. Next, optimized recombinant production RV-neutralizing, VP4-specific (mAb41) antibody. We then demonstrated IgG mAb41 lactating dams conferred from RV-induced diarrhea pups, with resulting lower incidence IgG. Systemic delivery engineered mAbs should be considered effective strategy sIgA to gastrointestinal tract via increase pathogens.