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.