SARS-CoV-2 Antibody Profiles in Maternal Serum and Breast Milk Following mRNA COVID-19 Vaccination: A Longitudinal Prospective Observational Cohort Study

Abstract

COVID-19 vaccination during pregnancy protects infants against symptomatic COVID-19. Vaccination of lactating mothers may offer additional protection, but our understanding of immune responses in breast milk is limited. We, therefore, performed a single-center prospective cohort study of lactating mothers who received a COVID-19 mRNA primary vaccine series to evaluate the durability, breadth, and neutralizing capacity of the antibody responses in breast milk. Spike IgG- and IgA-binding antibodies of ancestral SARS-CoV-2 in serum and breast milk were quantified over 9 months using Meso Scale Discovery (MSD) V-PLEX assays, and ancestral titers were compared to four variants of concern (Alpha, Beta, Delta, Gamma) at a single time point. Neutralizing antibodies against ancestral SARS-CoV-2 and Omicron BA.4/5 were compared before and after vaccination using a pseudovirus-neutralization assay. Eleven lactating mothers received either Pfizer BNT162b2 (7/11) or Moderna mRNA-1273 (4/11) vaccine primary series. IgG and IgA titers increased in serum and breast milk following each dose, peaking 1–4 weeks after series completion. Titers remained significantly elevated for 7–9 months, except for in breast milk IgA which returned to baseline within 1 month. Furthermore, binding antibodies against all included variants were detected in breast milk collected 1–3 weeks after series completion. However, while vaccination induced a strong neutralizing response against ancestral SARS-CoV-2 in serum and more modest response in breast milk, it did not induce neutralizing antibodies against Omicron BA.4/5 in either specimen type. This study demonstrates that maternal COVID-19 mRNA vaccination may enhance immune protection for infants through breast milk via increased IgG- and IgA-binding-and-neutralizing antibodies; although, variant-specific boosters may be required to optimize immune protection.