Biodistribution of mRNA COVID-19 Vaccines in Human Breast Milk

Biodistribution of mRNA COVID-19 Vaccines in Human Breast Milk — The Lancet

COVID-19 mRNA vaccines play a vital role in the fight against SARS-CoV-2 infection. However, lactating women have been largely excluded from most vaccine clinical trials.

As a result, limited research has been conducted on the systemic distribution of vaccine mRNA during lactation and whether it is excreted in human breast milk (BM).

Here, we evaluated if COVID-19 vaccine mRNA is detectable in BM after maternal vaccination and determined its potential translational activity…

Findings

Of 13 lactating women receiving the vaccine (20 exposures), trace mRNA amounts were detected in 10 exposures up to 45 h post-vaccination.

The mRNA was concentrated in the BM EVs; however, these EVs neither expressed SARS-COV-2 spike protein nor induced its expression in the HT-29 cell line. Linkage analysis suggests vaccine mRNA integrity was reduced to 12–25% in BM.

Interpretations

Our findings demonstrate that the COVID-19 vaccine mRNA is not confined to the injection site but spreads systemically and is packaged into BM EVs.

However, as only trace quantities are present and a clear translational activity is absent, we believe breastfeeding post-vaccination is safe, especially 48 h after vaccination.

Nevertheless, since the minimum mRNA vaccine dose to elicit an immune reaction in infants <6 months is unknown, a dialogue between a breastfeeding mother and her healthcare provider should address the benefit/risk considerations of breastfeeding in the first two days after maternal vaccination.

…. Initially, it was thought that the vaccine mRNA encapsulated in LNPs would remain localized at the injection site and quickly degrade.

However, several reports suggest that the LNPs/mRNA can enter the bloodstream and accumulate in distant tissues.

The Pfizer and Moderna Assessment Reports provided to the European Medicines Agency concluded that a small fraction of the administered mRNA dose was distributed to distant tissues, mainly the liver, adrenal glands, spleen, and ovaries. Additionally, mRNA constructs persisted for 1–3 days in tissues other than the injection site.

For lactating mothers receiving the vaccine, our results suggest that the vaccine LNPs will reach the breast tissue.

However, since the intact blood-milk barrier prevents an uncontrolled exchange of soluble and cellular components between blood and milk in the mammary gland it is unlikely that intact LNPs will pass the blood-milk barrier to the BM.

Using the fraction of RNA we detected in breast milk/mL, we calculated that the expected level of lipids in the same volume of milk was below the level of detection using the currently available analytical methodology.

Our model (Fig. 5) proposes that following intramuscular administration, the LNPs containing the vaccine mRNA are likely carried to mammary glands via hematogenous or lymphatic transport.

The LNPs will release their mRNA content into the cytosol of the mammary gland cells, and a portion of this mRNA will be recruited, packaged, and released in the BM EVs (exosomes or microvesicles).

This can be significant as the BM EVs act as natural LNPs, protecting the mRNA from degradation.

Milk-derived EVs are resistant to proteolysis by gastric and pancreatic secretions and can be readily absorbed by intestinal epithelial cells. Because of their ability to transfer and protect the mRNA, milk EVs have been tested as a vehicle for COVID mRNA oral vaccine.

SOURCE: The Lancet