孕期接种新型冠状病毒2型疫苗可通过γ干扰素反应性小胶质细胞增强子代海马神经发生和工作记忆。

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

作者信息

Tang Jiaoling, Qi Fangfang, Zou Juntao, Liu Hao, Zuo Zejie, Wang Lingxiao, Wang Na, Li Zhihui, Kumar Ashutosh, Guo Kaihua, Hu Dandan, Yao Zhibin

机构信息

Department of Anatomy and Physiology, Guangdong Province Key Laboratory of Brain Function and Disease, Advanced Medical Technology Center, The First Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.

Department of Neurology, Mayo Clinic, Rochester, MN, USA.

出版信息

Commun Biol. 2025 Aug 29;8(1):1307. doi: 10.1038/s42003-025-08691-8.

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.

面对新冠病毒疾病（COVID-19）的严重后果，疫苗已被证明具有免疫原性且安全，强烈建议在孕期接种。本研究考察了母体接种新冠疫苗对小鼠后代身体发育、行为及神经发生的影响。在妊娠第14.5天接种灭活严重急性呼吸综合征冠状病毒2（SARS-CoV-2）疫苗（Vero细胞）后，在母鼠和幼崽血清中检测到抗体。在1月龄时，接种疫苗母鼠的后代（而非对照组后代）表现出工作记忆增强、神经增殖增加、神经母细胞形成增多、干细胞活性增强以及齿状回（DG）中神经元更成熟。Luminex检测显示海马中干扰素γ（IFN-γ）和CX3趋化因子配体1（CX3CL1）升高，二者均与神经发生和记忆有关。条件性基因敲除实验确定小胶质细胞干扰素γ受体1（IFNγR1）和CX3趋化因子受体1（CX3CR1）是通过调节小胶质细胞激活和趋化作用来介导神经元发育的关键介质。这些发现表明，母体接种SARS-CoV-2疫苗可短暂增强后代海马神经发生和工作记忆，且不会造成神经发育风险。