Impact of Maternal COVID-19 Infection Versus Vaccination on Mucosal Immunity in Breastmilk.

Background/Objectives: In the first months of their life, infants rely on maternal antibodies for immune protection. Breastmilk is a major source of these defenses, supplying secretory IgA, IgG, and IgM that help guard mucosal surfaces against pathogens such as SARS-CoV-2. Most studies on breastmilk immunity in the context of COVID-19 have emphasized circulating monomeric IgA, rather than the multimeric secretory IgA (sIgA) that is active at mucosal barriers. This study assessed in-depth the contribution of breastmilk antibody subtypes to SARS-CoV-2 neutralization capacity and how these profiles differ following maternal COVID-19 infection versus vaccination during pregnancy or postpartum. Methods: In this prospective cohort study, breastmilk samples were collected longitudinally from individuals who had COVID-19 during pregnancy or received COVID-19 mRNA vaccination during pregnancy or postpartum. Serological assays measured IgG, IgM, systemic IgA, and secretory IgA against SARS-CoV-2 spike and nucleocapsid antigens. Results: COVID-19 infection during pregnancy resulted in significantly higher systemic and secretory IgA levels compared to vaccination. Secretory IgA demonstrated a strong correlation with neutralization capacity. Principal component analysis revealed distinct antibody profiles in COVID-19-exposed individuals versus vaccinated cohorts, with significant overlap between pregnancy and postpartum vaccination groups. Conclusions: Although both COVID-19 vaccination and disease elicit sustained COVID-19-related antibodies in breastmilk, COVID-19 infection elicits a broader and more diverse antibody response in breastmilk, specifically with a greater secretory IgA generation. These findings support the value of maternal vaccination to safely confer mucosal immunity to neonates and the need for optimized vaccine formulations for mucosal immunity.