Yona Tugg, McMaster University

Yona Tugg (1), Jann Ang (1), Imran Ahmed (1), Viraj Mane (2), Rikin Mehta (2), Sam Afkhami (1), Matthew S. Miller (1). 1. McMaster University. 2. Lactiga US, Inc

Fighting & Responding

Passive immunization strategies play a critical role in bridging the gap between the onset of a pandemic or outbreak and the widespread implementation of specific vaccines. Current passive immunization approaches rely on intravenously administered plasma or monoclonal antibodies, which pose challenges for individuals requiring frequent treatment, such as immunocompromised patients. Additionally, these methods are difficult to deploy as prophylactic measures during outbreaks. As such, novel therapeutic options must be considered. Mucosally administered antibodies represent a promising alternative to traditional intravenous delivery, especially for respiratory pathogens. However, large-scale production of respiratory mucosal antibodies is limited by invasive and costly collection methods. Breast milk offers an accessible and abundant source of mucosal antibodies, particularly secretory IgA (sIgA). To evaluate its therapeutic potential, we investigated the antiviral properties of breast milk–derived sIgA. Breast milk–derived sIgA demonstrated broad antiviral activity against representative strains of influenza A virus (IAV), respiratory syncytial virus (RSV), and adenovirus. ELISA and microneutralization assays showed binding and neutralization of both group 1 and group 2 IAV strains. Additionally, breast milk-derived sIgA had neuraminidase inhibition and Fc-dependent effector activity, measured by enzyme-linked lectin assay (ELLA) and luminol-based detection. Notably, sIgA also bound the emerging H5N1 2.3.4.4b variant and mediated Fc-effector functions. In vivo, intranasal administration of sIgA protected immunocompetent and immunocompromised mice from IAV-associated morbidity and mortality, reducing tissue damage and dampening inflammatory responses. Together, our findings highlight sIgA as a promising alternative passive immunization strategy for respiratory infections.