SARS-CoV-2 vaccination during pregnancy enhances offspring hippocampal neurogenesis and working memory via IFN-γ–responsive microglia

In the face of severe outcomes from COVID-19, vaccines have proven immunogenic and safe and are strongly recommended during pregnancy. This study examines the effects of maternal COVID-19 vaccination on physical development, behavior, and neurogenesis in mouse offspring. After inoculation with inactivated SARS-CoV-2 vaccine (Vero Cell) at gestational day 14.5, antibodies were detected in the serum of dams and pups. At one month of age, offspring of vaccinated dams-but not controls-showed enhanced working memory, increased neural proliferation, neuroblast formation, stem cell activity, and more mature neurons in the dentate gyrus (DG). Luminex assay showed elevated hippocampal IFN-γ and CX3CL1, both linked to neurogenesis and memory. Conditional knockout experiments identified microglial IFNγR1 and CX3CR1 as key mediators of neuronal development through regulating microglial activation and chemotaxis. These findings suggest maternal SARS-CoV-2 vaccination transiently enhances hippocampal neurogenesis and working memory in offspring, without causing neurodevelopmental risk.