mRNA-1273 is placenta-permeable and immunogenic in the fetus

Area of Science:

• Immunology
• Pharmacology
• Vaccinology

Background:

• COVID-19 mRNA vaccines are widely used during pregnancy.
• The transplacental transfer and fetal effects of these vaccines are not fully understood.

Purpose of the Study:

• To investigate the pharmacokinetics and immunogenicity of mRNA-1273 vaccine administered during pregnancy in a mouse model.
• To determine the potential for fetal immune response and protection against SARS-CoV-2.

Main Methods:

• Pregnant mice were intramuscularly administered mRNA-1273.
• Transplacental transfer, fetal circulation, tissue accumulation, and translation of mRNA were analyzed.
• Fetal immunogenicity was assessed by measuring anti-spike IgM, IgG2a, and cellular immunity postnatally.

Main Results:

• mRNA-1273 rapidly crossed the placenta, with mRNA detected in fetal circulation within 1 hour.
• Fetal tissues, particularly the liver, accumulated mRNA and translated it into spike protein.
• Transplacental mRNA-1273 induced fetal immunogenicity, including anti-spike IgM, IgG2a, and cellular immunity.
• Higher vaccine doses resulted in increased transplacental transfer and fetal immune responses.

Conclusions:

• Gestational maternal mRNA-1273 vaccination can lead to fetal exposure and active immunization.
• This process may confer both passive and active anti-SARS-CoV-2 immunity to newborns.
• Findings advance understanding of mRNA vaccine transfer and immunogenic potential in fetuses, supporting prenatal mRNA therapy concepts.