Vaccination is a cornerstone in the fight against the COVID-19 pandemic. However, early clinical trials of the messenger RNA (mRNA) vaccine excluded several vulnerable groups, such as young children and breastfeeding individuals(1). The U.S. Food and Drug Administration has deferred a decision to license COVID-19 mRNA vaccines for infants younger than 6 months until more data are available, because of possible priming of immune responses in infants that could impair their immunity.(2)
The Centers for Disease Control and Preventions recommends that COVID-19 mRNA vaccines be offered to persons who are breastfeeding, although the possible passage of vaccine mRNA into breast milk resulting in exposure of infants younger than 6 months has not been studied. This study examined whether COVID-19 mRNA vaccine can be detected in expressed breast milk (EBM) from breastfeeding persons who receive the vaccine within 6 months postpartum.
This cohort study included 11 healthy breastfeeding individuals who received either the Moderna mRNA-1273 (n = 5) or Pfizer BNT162b2 (n = 6) vaccine within 6 months postpartum (Table 1). Participants were asked to collect and immediately freeze EBM samples at home until they were transported to the laboratory. EBM samples were collected before vaccination (control) and for 5 days after vaccination. A total of 131 EBM samples were collected between 1 hour and 5 days after vaccine administration. Extracellular vesicles (EVs) were isolated from EBM by sequential centrifugation, and EV concentrations were determined by ZetaView (Analytik) (eMethods in the Supplement). The presence of COVID-19 mRNA in different milk fractions (whole MBE, fat, cells, and EV supernatant) was determined by a two-step quantitative reverse transcriptase polymerase chain reaction. The vaccine detection limit was 1 pg/mL EBM (eMethods in the Supplement).
Of the 11 enrollees who were breastfeeding, trace amounts of BNT162b2 mRNA and COVID-19 mRNA-1273 vaccines were detected in 7 samples from 5 different participants at various times up to 45 hours after vaccination (Table 2 ). The mean (SD) yield of EVs isolated with EBM was 9.1 (5.0) particles/mL, and the mean (SD) particle size was 110.0 (3.0) nm. Vaccine mRNA appeared in higher concentrations in EVs than in whole milk (Table 2). No vaccine mRNA was detected in pre- or post-vaccination EBM samples beyond 48 hours of collection. In addition, COVID-19 vaccine mRNA was not detected in the fat fraction of EBM or in EBM cell pellets.
The sporadic presence and traces of COVID-19 mRNA detected in EBM suggest that breastfeeding after vaccination with COVID-19 mRNA is safe, especially beyond 48 hours post-vaccination. These data demonstrate for the first time, to our knowledge, the biodistribution of COVID-19 mRNA in mammary cells and the potential ability of tissue EVs to package vaccine mRNA that can be transported to distant cells. Little has been reported on the biodistribution and localization of lipid nanoparticles in human tissues following vaccination with COVID-19 mRNA. In rats, up to 3 days after intramuscular administration, low levels of vaccine mRNA were detected in heart, lung, testis, and brain tissues, indicating tissue biodistribution. (4) It is hypothesized that, after vaccine administration, lipid nanoparticles containing vaccine mRNA are transported to the mammary glands via the hematogenous and/or lymphatic pathways. 5, 6 Furthermore, it is hypothesized that vaccine mRNA released into the cytosol of mammary cells may be recruited for the development of EVs that are subsequently secreted into the EBM.