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

Abstract

In the face of severe adverse outcomes of pandemic Coronavirus disease 2019 (COVID-19) infection, vaccines proved potently immunogenic and safe in humans and are today strongly recommended in pregnancy. This study investigates, in offspring mice, the effect of maternal COVID-19 vaccination on postnatal physical development, behavior and neurogenesis. After inoculation with inactivated COVID-19 vaccine (Vero Cell) at gestational day 14.5, antibodies to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were detected in serum of both dams and pups. At one month of age, pups born to vaccinated dams, but not the offspring of non-vaccinated dams, exhibited greater working memory and more neural cell proliferation, neuroblast formation, neuronal stem cell activity and larger numbers of mature neurons within the dentate gyrus (DG). Luminex multiplex assay revealed elevated levels of hippocampal cytokines/chemokines critical to neurogenesis and memory function, namely interferon-{gamma} [IFN-{gamma}] and CX3C motif chemokine ligand 1 [CX3CL1]. Conditional knockout technology implicated microglial IFN-{gamma} receptor 1 (IFN{gamma}R1) and CX3C motif chemokine receptor 1 (CX3CR1) as crucial intercellular participants in the neuronal developmental process, via regulating microglial activation and chemotaxis, respectively. We propose that, rather than posing risk for neurodevelopmental abnormalities, maternal SARS-CoV-2 vaccination transiently enhances hippocampal neurogenesis and working memory in offspring.