mRNA-1273 is Placenta-Permeable and Immunogenic in the Fetus

Abstract Summary

• COVID-19 mRNA Vaccines: Generally recognized as safe for gestational administration, but transplacental pharmacokinetics are not well understood.
• Study Overview:
  • Subject: Pregnant mice.
  • Vaccine: mRNA-1273 given intramuscularly.
  • Findings:
    • Rapid circulation in maternal blood.
    • Crosses placenta within one hour and spreads in fetal circulation.
    • Spike mRNA fades in fetal circulation within 4-6 hours, but accumulates in fetal tissues (primarily liver).
    • Translated into spike protein.

Immunogenic Effects

• Fetal Immunity: Transplacental mRNA-1273 is immunogenic:
  • Postnatal presence of anti-spike IgM.
  • Paternal allotypic anti-spike IgG2a.
  • Enhanced anti-spike cellular immunity.

Dose-Dependent Effects

• Transplacental Transfer: Dose-dependent effect noted:
  • Higher doses lead to increased mRNA transfer.
  • Greater serum titers of endogenous anti-spike IgM/IgG in fetuses.
• Implications:
  • Gestational mRNA-1273 vaccination potentially provides both passive and active immunity to newborns.

Broader Implications

• New Insights: Illuminates the transplacental capacity and immunogenic potential of mRNA vaccines in fetuses.
• Advancement in mRNA Medicine: Potential to protect unborns against pathogens during perinatal life.
• Expansion of Prenatal Molecular Therapy: Suggests broader applications for prenatal mRNA therapy.

Publication Information

• Rights: Published under a Creative Commons license by Elsevier Inc. on behalf of The American Society of Gene and Cell Therapy.
• Citations: Article not yet cited.
• Published: 2025 by the Author(s).