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Vaccine-induced COVID-19 mimicry syndrome

To fight the COVID-19 pandemic caused by the RNA virus SARS-CoV-2, a global vaccination campaign is in progress to achieve the immunization of billions of people mainly with adenoviral vector- or mRNA-based vaccines, all of which encode the SARS-CoV-2 Spike protein. In some rare cases, cerebral veno...

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Autores principales: Kowarz, Eric, Krutzke, Lea, Külp, Marius, Streb, Patrick, Larghero, Patrizia, Reis, Jennifer, Bracharz, Silvia, Engler, Tatjana, Kochanek, Stefan, Marschalek, Rolf
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8846585/
https://www.ncbi.nlm.nih.gov/pubmed/35084333
http://dx.doi.org/10.7554/eLife.74974
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author Kowarz, Eric
Krutzke, Lea
Külp, Marius
Streb, Patrick
Larghero, Patrizia
Reis, Jennifer
Bracharz, Silvia
Engler, Tatjana
Kochanek, Stefan
Marschalek, Rolf
author_facet Kowarz, Eric
Krutzke, Lea
Külp, Marius
Streb, Patrick
Larghero, Patrizia
Reis, Jennifer
Bracharz, Silvia
Engler, Tatjana
Kochanek, Stefan
Marschalek, Rolf
author_sort Kowarz, Eric
collection PubMed
description To fight the COVID-19 pandemic caused by the RNA virus SARS-CoV-2, a global vaccination campaign is in progress to achieve the immunization of billions of people mainly with adenoviral vector- or mRNA-based vaccines, all of which encode the SARS-CoV-2 Spike protein. In some rare cases, cerebral venous sinus thromboses (CVST) have been reported as a severe side effect occurring 4–14 days after the first vaccination and were often accompanied by thrombocytopenia. Besides CVST, splanchnic vein thromboses (SVT) and other thromboembolic events have been observed. These events only occurred following vaccination with adenoviral vector-based vaccines but not following vaccination with mRNA-based vaccines. Meanwhile, scientists have proposed an immune-based pathomechanism and the condition has been coined vaccine-induced immune thrombotic thrombocytopenia (VITT). Here, we describe an unexpected mechanism that could explain thromboembolic events occurring with DNA-based but not with RNA-based vaccines. We show that DNA-encoded mRNA coding for Spike protein can be spliced in a way that the transmembrane anchor of Spike is lost, so that nearly full-length Spike is secreted from cells. Secreted Spike variants could potentially initiate severe side effects when binding to cells via the ACE2 receptor. Avoiding such splicing events should become part of a rational vaccine design to increase safety of prospective vaccines.
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spelling pubmed-88465852022-02-16 Vaccine-induced COVID-19 mimicry syndrome Kowarz, Eric Krutzke, Lea Külp, Marius Streb, Patrick Larghero, Patrizia Reis, Jennifer Bracharz, Silvia Engler, Tatjana Kochanek, Stefan Marschalek, Rolf eLife Cell Biology To fight the COVID-19 pandemic caused by the RNA virus SARS-CoV-2, a global vaccination campaign is in progress to achieve the immunization of billions of people mainly with adenoviral vector- or mRNA-based vaccines, all of which encode the SARS-CoV-2 Spike protein. In some rare cases, cerebral venous sinus thromboses (CVST) have been reported as a severe side effect occurring 4–14 days after the first vaccination and were often accompanied by thrombocytopenia. Besides CVST, splanchnic vein thromboses (SVT) and other thromboembolic events have been observed. These events only occurred following vaccination with adenoviral vector-based vaccines but not following vaccination with mRNA-based vaccines. Meanwhile, scientists have proposed an immune-based pathomechanism and the condition has been coined vaccine-induced immune thrombotic thrombocytopenia (VITT). Here, we describe an unexpected mechanism that could explain thromboembolic events occurring with DNA-based but not with RNA-based vaccines. We show that DNA-encoded mRNA coding for Spike protein can be spliced in a way that the transmembrane anchor of Spike is lost, so that nearly full-length Spike is secreted from cells. Secreted Spike variants could potentially initiate severe side effects when binding to cells via the ACE2 receptor. Avoiding such splicing events should become part of a rational vaccine design to increase safety of prospective vaccines. eLife Sciences Publications, Ltd 2022-01-27 /pmc/articles/PMC8846585/ /pubmed/35084333 http://dx.doi.org/10.7554/eLife.74974 Text en © 2022, Kowarz et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Kowarz, Eric
Krutzke, Lea
Külp, Marius
Streb, Patrick
Larghero, Patrizia
Reis, Jennifer
Bracharz, Silvia
Engler, Tatjana
Kochanek, Stefan
Marschalek, Rolf
Vaccine-induced COVID-19 mimicry syndrome
title Vaccine-induced COVID-19 mimicry syndrome
title_full Vaccine-induced COVID-19 mimicry syndrome
title_fullStr Vaccine-induced COVID-19 mimicry syndrome
title_full_unstemmed Vaccine-induced COVID-19 mimicry syndrome
title_short Vaccine-induced COVID-19 mimicry syndrome
title_sort vaccine-induced covid-19 mimicry syndrome
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8846585/
https://www.ncbi.nlm.nih.gov/pubmed/35084333
http://dx.doi.org/10.7554/eLife.74974
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