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

COVID-19 mRNA vaccines are generally recognized as safe for gestational administration. However, their transplacental pharmacokinetics remain obscure. In this study, mRNA-1273 intramuscularly given to pregnant mice rapidly circulated in maternal blood and crossed the placenta within 1 h to spread in the fetal circulation. Although spike mRNA in fetal circulation faded away within 4-6 h, it could accumulate in fetal tissues, mainly the liver and get translated into spike protein. Transplacental mRNA-1273 proved immunogenic in the fetuses, as postnatally equipped with anti-spike immunoglobulin (Ig)M, paternal allotypic anti-spike IgG_2a, and heightened anti-spike cellular immunity. Gestationally administered, mRNA-1273 had a dose-dependent effect on its transplacental transfer and immunogenicity in the fetuses, with higher mRNA-1273 doses leading to increased transplacental mRNA-1273 passage and greater serum titers of endogenous anti-spike IgM/IgG generated by the fetuses. Thus, gestationally maternal mRNA-1273 vaccination might endow the newborns with not only passive but also active anti-spike immunity. Our results pose new insights into transplacental capacity of mRNA vaccines and their immunogenic potential in the fetuses, advancing our knowledge of mRNA medicine to protect the unborns against pathogens in perinatal life and broaden our horizons of prenatal mRNA molecular therapy.