The COVID-19 RNA vaccine SpikevaxTM transfects human umbilical endothelial cells and induces Spike protein production, inflammation and leukocyte adhesion
- 1Center for Research in Medical Pharmacology
Abstract
Endothelial cell dysfunction plays a key role in the pathogenesis of severe and critical COVID-19, leading to a multi-systemic inflammatory disease, and results from the direct interaction of the SARS-CoV-2 Spike proteins with endothelial cells. COVID-19 RNA vaccines encode a recombinant SARS-CoV-2 Spike protein which undergoes systemic biodistribution. No information is however so far available on the direct effects of COVID-19 RNA vaccines on human endothelial cells. In the present study, we exposed cultured human umbilical venous endothelial cells (HUVEC) to the COVID-19 RNA vaccine SpikevaxTM (Moderna, Inc.), and thereafter we measured the expression of the Spike protein, of the proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-, of the adhesion molecules intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), as well as the attachment of human leukocytes to HUVEC layers. We also assessed the effects of SpikevaxTM on HUVEC viability. Exposure of HUVEC to the COVID-19 RNA vaccine SpikevaxTM resulted in effective cell transfection, and subsequent production of the Spike protein, which was expressed in the cells and secreted in the culture medium. Spike protein production was accompanied by increased gene expression of IL-6 and TNF- and of ICAM-1 and VCAM-1, as well as by increased attachment of leukocytes to HUVEC monolayers. Exposure to the COVID-19 RNA vaccine SpikevaxTM did not affect HUVEC viability. Our results provide a mechanistic explanation to post-COVID-19 RNA vaccination pathologies resulting from endothelial dysfunction, such as during atherosclerosis, autoimmune inflammation, and systemic inflammatory conditions.
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BibTeX
@misc{cosentino2026covid19,
title = {{The COVID-19 RNA vaccine SpikevaxTM transfects human umbilical endothelial cells and induces Spike protein production, inflammation and leukocyte adhesion}},
author = {M. Cosentino and M. Ferrari and N. Schiavone and E. Rasini and A. Luini and M. Legnaro and M. Federico and F. Marino and G. Frajese},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.15.751712},
url = {https://www.biorxiv.org/content/10.64898/2026.09.15.751712v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - The COVID-19 RNA vaccine SpikevaxTM transfects human umbilical endothelial cells and induces Spike protein production, inflammation and leukocyte adhesion
AU - M. Cosentino
AU - M. Ferrari
AU - N. Schiavone
AU - E. Rasini
AU - A. Luini
AU - M. Legnaro
AU - M. Federico
AU - F. Marino
AU - G. Frajese
PY - 2026
DA - 2026/09/15
PB - bioRxiv
DO - 10.64898/2026.09.15.751712
UR - https://www.biorxiv.org/content/10.64898/2026.09.15.751712v1
AB - Endothelial cell dysfunction plays a key role in the pathogenesis of severe and critical COVID-19, leading to a multi-systemic inflammatory disease, and results from the direct interaction of the SARS-CoV-2 Spike proteins with endothelial cells. COVID-19 RNA vaccines encode a recombinant SARS-CoV-2 Spike protein which undergoes systemic biodistribution. No information is however so far available on the direct effects of COVID-19 RNA vaccines on human endothelial cells. In the present study, we exposed cultured human umbilical venous endothelial cells (HUVEC) to the COVID-19 RNA vaccine SpikevaxTM (Moderna, Inc.), and thereafter we measured the expression of the Spike protein, of the proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-, of the adhesion molecules intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), as well as the attachment of human leukocytes to HUVEC layers. We also assessed the effects of SpikevaxTM on HUVEC viability. Exposure of HUVEC to the COVID-19 RNA vaccine SpikevaxTM resulted in effective cell transfection, and subsequent production of the Spike protein, which was expressed in the cells and secreted in the culture medium. Spike protein production was accompanied by increased gene expression of IL-6 and TNF- and of ICAM-1 and VCAM-1, as well as by increased attachment of leukocytes to HUVEC monolayers. Exposure to the COVID-19 RNA vaccine SpikevaxTM did not affect HUVEC viability. Our results provide a mechanistic explanation to post-COVID-19 RNA vaccination pathologies resulting from endothelial dysfunction, such as during atherosclerosis, autoimmune inflammation, and systemic inflammatory conditions.
ER -