Division of Basic Science and Translational Research, Department of Obstetrics & Gynecology, The University of Texas Medical Branch at Galveston, Galveston, Texas, USA.
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
Am J Reprod Immunol. 2024 May;91(5):e13861. doi: 10.1111/aji.13861.
Maternal-fetal immunology is intricate, and the effects of mRNA-S maternal vaccination on immune regulation at the maternal-fetal interface require further investigation. Our study endeavors to elucidate these immunological changes, enhancing our comprehension of maternal and fetal health outcomes. By analyzing immune profiles and cytokine responses, we aim to provide valuable insights into the impact of mRNA-S vaccination on the delicate balance of immune regulation during pregnancy, addressing critical questions in the field of reproductive pharmacology.
This investigation sought to examine the prospective influence of mRNA-S-based vaccines and extracellular vesicles (EVs) containing the Spike (S) protein at the maternal-fetal interface. Our primary emphasis was on evaluating their effects on maternal decidua cells and fetal chorion trophoblast cells (hFM-CTCs).
We validated the generation of EVs containing the S protein from small human airway epithelial cell lines (HSAECs) following mRNA-S vaccine exposure. We assessed the expression of angiotensin-converting enzyme 2 (ACE2) gene and protein in fetal membranes and the placenta, with specific attention to decidual cells and fetal membrane chorion cells. To assess cellular functionality, these cells were exposed to both recombinant S protein and EVs loaded with S proteins (eSPs).
Our findings revealed that cells and EVs subjected to mRNA-S-based vaccination exhibited altered protein expression levels of S proteins. At the feto-maternal interface, both placental and fetal membrane tissues demonstrated similar ACE-2 expression levels. Among individual cellular layers, syncytiotrophoblast cells in the placenta and chorion cells in the fetal membrane exhibited elevated ACE-2 expression. Notably, EVs derived from HSAECs activated the MAPK pathway in decidual cells. Additionally, decidual cells displayed a substantial increase in gene expression of chemokines like CXCL-10 and CXCL-11, as well as proinflammatory cytokines such as IL-6 in response to eSPs. However, the levels of Ccl-2 and IL-1β remained unchanged in decidual cells under the same conditions. Conversely, hFM-CTCs demonstrated significant alterations in the proinflammatory cytokines and chemokines with respect to eSPs.
In conclusion, our study indicates that mRNA-S-based maternal vaccination during pregnancy may influence the maternal-fetal interface's COVID-19 interaction and immune regulation. Further investigation is warranted to assess safety and implications.
母胎免疫学十分复杂，mRNA-S 疫苗对母胎界面免疫调节的影响需要进一步研究。我们的研究旨在阐明这些免疫变化，增进我们对母婴健康结局的理解。通过分析免疫谱和细胞因子反应，我们旨在为 mRNA-S 疫苗接种对妊娠期间免疫调节平衡的影响提供有价值的见解，解决生殖药理学领域的关键问题。
本研究旨在检测基于 mRNA-S 的疫苗和含有 Spike（S）蛋白的细胞外囊泡（EVs）在母胎界面的前瞻性影响。我们的主要重点是评估它们对母体蜕膜细胞和胎儿绒毛膜滋养层细胞（hFM-CTCs）的影响。
我们验证了从小人呼吸道上皮细胞系（HSAECs）中产生含有 S 蛋白的 EVs 后，mRNA-S 疫苗的暴露。我们评估了胎儿膜和胎盘中血管紧张素转换酶 2（ACE2）基因和蛋白的表达，特别关注蜕膜细胞和胎儿膜绒毛膜细胞。为了评估细胞功能，这些细胞暴露于重组 S 蛋白和负载 S 蛋白的 EVs（eSPs）。
我们的研究结果表明，细胞和 EVs 经过 mRNA-S 疫苗接种后，S 蛋白的蛋白表达水平发生了改变。在胎儿母体界面，胎盘和胎儿膜组织均表现出相似的 ACE-2 表达水平。在单个细胞层中，胎盘的合体滋养层细胞和胎儿膜的绒毛膜细胞表现出 ACE-2 的高表达。值得注意的是，源自 HSAECs 的 EVs 激活了蜕膜细胞中的 MAPK 途径。此外，蜕膜细胞的趋化因子（如 CXCL-10 和 CXCL-11）和促炎细胞因子（如 IL-6）的基因表达显著增加，以响应 eSPs。然而，在相同条件下，蜕膜细胞中的 Ccl-2 和 IL-1β 水平保持不变。相反，hFM-CTCs 对 eSPs 的炎症细胞因子和趋化因子表现出显著的改变。
总之，我们的研究表明，妊娠期间基于 mRNA-S 的母体疫苗接种可能会影响母胎界面的 COVID-19 相互作用和免疫调节。需要进一步研究以评估安全性和影响。
