In vitro mRNA‐S maternal vaccination induced altered immune regulation at the maternal‐fetal interface

Author:

Kammala Ananth Kumar1ORCID,Tatiparthy Madhuri1,Thomas Tilu Jain1,Bonam Srinivasa Reddy2,Boldogh Istvan34,Haitao Hu25,Sharma Surendra1,Menon Ramkumar1ORCID

Affiliation:

1. Division of Basic Science and Translational Research, Department of Obstetrics & Gynecology The University of Texas Medical Branch at Galveston Galveston Texas USA

2. Department of Microbiology and Immunology University of Texas Medical Branch Galveston Texas USA

3. Director of Cell Biology Core Laboratory, Department of Microbiology University of Texas Medical Branch Galveston Texas USA

4. Sealy Institute for Vaccine Sciences University of Texas Medical Branch Galveston Texas USA

5. Institute for Human Infections and Immunity University of Texas Medical Branch Galveston Texas USA

Abstract

AbstractBackgroundMaternal‐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.ObjectivesThis 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).MethodsWe 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).ResultsOur 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.ConclusionIn 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.

Publisher

Wiley

Reference65 articles.

1. Prevention. CfDCa. COVID Data Tracker.

2. COVID-19 and the heart

3. ADMINISTRATION USFD.FDA Approves First COVID‐19 Vaccine.https://www.fda.gov/news‐events/press‐announcements/fda‐approves‐first‐covid‐19‐vaccine

4. Characteristics and outcomes of pregnant women admitted to hospital with confirmed SARS-CoV-2 infection in UK: national population based cohort study

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3