A Double-Edged Sword: Breast Milk-Derived Maternal Antibodies and Infant Vaccine Responses: A Narrative Review

Neonatal defense against pathogens relies on maternal antibodies transferred both through the placenta (IgG) and through breast milk (primarily secretory IgA). Maternal IgG antibodies are transferred across the placenta to the fetus mainly via the neonatal Fc receptor (FcRn), which is expressed at high levels in placental syncytiotrophoblasts, and results in the acquisition of maternal-fetal IgG. Transplacental transfer via the FcRn pathway can provide therapeutic proteins and protective antibodies following maternal vaccination. However, maternal IgG antibodies can bind to vaccine antigens such as measles, tetanus, and poliovirus, resulting in rapid clearance through FcgRIIB-mediated inhibition and inadequate B cell activation. In this way, they can inhibit de novo immune responses and significantly reduce vaccine response. On the other hand, the interference that breast milk-derived antibodies may have on vaccine-induced immunity is still largely unknown. Vaccination against influenza, pertussis, and COVID-19 during pregnancy or lactation has been shown to induce the production of protective, pathogen-specific, secretory IgA and IgG antibodies in breast milk. Conversely, studies found that breast milk-derived antibodies of vaccinated mothers reduced vaccine-induced immunity in breastfed infants by accelerating the clearance of vaccine antigen, resulting in reduced antigen availability and reduced plasma cell formation after vaccination. Additional factors in middle- and low-income countries, including environmental (increased microbiome diversity, environmental intestinal dysfunction, malnutrition, co-infections) and breastfeeding practices, may exacerbate the interference effect of maternal antibodies. Current evidence supports that breastfeeding is associated with a reduced immunological response exclusively to the rotavirus vaccine. However, the limited evidence base to date precludes definitive conclusions regarding the role of breast milk-derived antibodies in modulating vaccine-induced immunity. Nevertheless, the evidence suggests that although maternal antibodies may theoretically reduce vaccine immunogenicity, the overall protective benefits of breastfeeding outweigh any potential interference with vaccine responses.