Single-cell mapping of peripheral immune dynamics in pregnant women after Moderna mRNA COVID-19 vaccination

Pregnant individuals are at increased risk of severe outcomes from COVID-19 infection, yet the immune responses elicited by vaccination during pregnancy remain poorly understood. In this study, longitudinal single-cell RNA sequencing (scRNA-seq) was performed on peripheral blood mononuclear cells from three pregnant women at four time points: before vaccination, one and two weeks after the first dose of the Moderna mRNA vaccine, and after the second dose postpartum. Dynamic immune changes, including a transient increase in inflammatory classical monocytes (cM_1) after the first dose, marked by elevated expression of IL1B, NLRP3 and NFKB1, as well as moderate activation of interferon-stimulated genes were observed. CD4⁺ T cells exhibited activation and differentiation into memory subsets. By contrast, B cell responses were minimal after the first dose, and enhanced protein synthesis activity emerged only after the second dose, which suggested delayed humoral activation. Although limited by sample size, our findings indicate that vaccination in pregnancy induces a nonexcessive innate immune activation, coordinated T cell responses and attenuated B cell activity that likely reflect pregnancy-driven immunoregulatory adaptations. These findings reveal the immune dynamics following mRNA vaccination during pregnancy and highlight the importance of developing vaccination strategies tailored for pregnant individuals.