Antibody Detection of Vaccine-induced Secretory Effects (ADVISE): A Prospective Study of Lactating Mothers Who Receive sars-cov-2 Vaccination

Background: The CDC recommends SARS-CoV-2 (COVID-19) vaccination for all adults, but vaccine safety for breastfeeding dyads and potential effects on lactation remain incompletely understood. Breastmilk immunological responses also have not been fully elucidated after COVID vaccination, specifically the formation of secretory IgA antibodies against viral Spike protein.

Methods: ADVISE (NCT04895475) is a prospective trial evaluating breastmilk antibodies among lactating women who receive COVID vaccination. Maternal and infant demographics, breastfeeding characteristics including exclusivity, and vaccination type and side-effects were recorded. Milk samples before vaccination, and weekly after Dose 1 and Dose 2, were delivered using a convenient drop-off system. Maternal blood samples at monthly intervals, along with optional infant samples using a finger-stick Mitra® microsampler device (Neoteryx), were also collected. Breastmilk was frozen at -80C until processing, and fat-free supernatant was tested for quantitative ELISA titers against SARS-CoV-2 Spike protein and neutralizing activity using a pseudo-virus blocking assay.

Results: A total of 66 women were consented, 3 of whom withdrew before data or sample collection. Of the remaining 63 (55 White, 5 Black, 3 Other), the median maternal age was 34.7 years (range 23.2-42.7 years); 36 received the Moderna vaccine series and 27 received the Pfizer series. The median infant age at enrollment was 6 months; most were born full-term except 3 at <32 weeks and 5 at 33-36 weeks. Three mothers (5%) reported vaccine-related lactation side-effects including 2 with a temporary decrease in milk supply and 1 who reported transient blue discoloration of the milk. Secretory IgA Spike antibodies (1:4 dilution, OD >0.5) were detected in the initial breastmilk samples from 14% of mothers, almost all of whom had either documented COVID infection or vaccination during pregnancy. For women who received vaccination while breastfeeding, 78% of the lactating mothers had secretory IgA antibodies in breastmilk within 2 weeks, which then dropped in titer and prevalence until the booster vaccine dose (Figure). Maximum breastmilk IgA titers were not associated with specific maternal or infant characteristics, including vaccine manufacturer. IgG breastmilk antibodies were also detected after the first vaccine, but titers were consistently high and sustained after the second dose (Figure). In preliminary analyses, most breastmilk samples had measurable neutralizing activity. Blood from mothers (1:400 dilution) had variable IgA responses but consistent IgG antibodies against Spike protein. In contrast, blood from infants only contained detectable Spike IgG and IgA antibodies if their mothers had COVID infection or vaccination during pregnancy, with no evidence that breastmilk antibodies transfer into the infant circulation.

Conclusion: COVID vaccination during lactation is well tolerated with few side-effects and generates a strong immune response. Secretory IgA antibodies are routinely detected in breastmilk and have viral neutralizing activity, supporting wider immunization among breastfeeding mothers.