Biodistribution of mRNA COVID-19 vaccines in human breast milk

Nazeeh Hanna; Claudia Manzano De Mejia; Ari Heffes-Doon; Xinhua Lin; Bishoy Botros; Ellen Gurzenda; Christie Clauss-Pascarelli; Amrita Nayak

doi:10.1016/j.ebiom.2023.104800

Biodistribution of mRNA COVID-19 vaccines in human breast milk

EBioMedicine. 2023 Oct:96:104800. doi: 10.1016/j.ebiom.2023.104800. Epub 2023 Sep 19.

Authors

Nazeeh Hanna¹, Claudia Manzano De Mejia², Ari Heffes-Doon³, Xinhua Lin², Bishoy Botros², Ellen Gurzenda², Christie Clauss-Pascarelli⁴, Amrita Nayak³

Affiliations

¹ Division of Neonatology, Department of Pediatrics, NYU Langone Hospital-Long Island, New York University Grossman Long Island School of Medicine, 259 First Street, Mineola, NY 11501, USA; Women and Children's Research Laboratory, New York University Grossman Long Island School of Medicine, 259 First Street, Mineola, NY 11501, USA. Electronic address: Nazeeh.Hanna@nyulangone.org.
² Women and Children's Research Laboratory, New York University Grossman Long Island School of Medicine, 259 First Street, Mineola, NY 11501, USA.
³ Division of Neonatology, Department of Pediatrics, NYU Langone Hospital-Long Island, New York University Grossman Long Island School of Medicine, 259 First Street, Mineola, NY 11501, USA.
⁴ Department of Pharmacy, NYU Langone Hospital-Long Island, New York University Grossman Long Island School of Medicine, 259 First Street, Mineola, NY 11501, USA.

Abstract

Background: 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.

Methods: We collected BM samples from 13 lactating, healthy, post-partum women before and after COVID-19 mRNA vaccination. Vaccine mRNA in whole BM and BM extracellular vesicles (EVs) was assayed using quantitative Droplet Digital PCR, and its integrity and translational activity were evaluated.

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.

Interpretation: 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.

Funding: This study was supported by the Department of Pediatrics, NYU-Grossman Long Island School of Medicine.

Keywords: Biodistribution; Breast milk; COVID-19; Extracellular vesicles; Lipid nanoparticles; Vaccine mRNA.