Polyclonal breast milk–derived secretory IgA confers broad antiviral protection against multiple respiratory viruses

Passive immunization is an important tool for protecting individuals with primary immune deficiencies from infectious diseases and offers a rapid response strategy for protecting vulnerable populations, particularly during the interval between pathogen emergence and vaccine deployment. Current approaches rely on intravenous delivery of IgG-enriched plasma or monoclonal antibodies, which limits accessibility, scalability, and effectiveness at mucosal surfaces, the primary entry point for respiratory viruses. Here, we tested LCTG-001, a polyclonal secretory IgA preparation derived from pooled human breast milk, to address these limitations. LCTG-001 demonstrated broad antiviral activity against clinically relevant respiratory viruses, including respiratory syncytial virus, adenovirus, and influenza A virus. LCTG-001 effectively recognized both group 1 and group 2 influenza A subtypes, including the highly pathogenic H5N1 clade 2.3.4.4b, and engaged nonneutralizing effector mechanisms such as neuraminidase inhibition and neutrophil activation. When administered intranasally, LCTG-001 conferred complete protection against influenza A challenge in both immunocompetent and antibody-deficient murine models, preventing morbidity and mortality through a transient early reduction in viral burden followed by sustained improvements in lung pathology and lung barrier integrity. These findings highlight the potential of breast milk-derived secretory IgA as a scalable, mucosa-targeted passive immunization strategy capable of addressing both endemic and emerging respiratory viral threats.