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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-01-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/74974 |
| _version_ | 1811201585138630656 |
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| author | Eric Kowarz Lea Krutzke Marius Külp Patrick Streb Patrizia Larghero Jennifer Reis Silvia Bracharz Tatjana Engler Stefan Kochanek Rolf Marschalek |
| author_facet | Eric Kowarz Lea Krutzke Marius Külp Patrick Streb Patrizia Larghero Jennifer Reis Silvia Bracharz Tatjana Engler Stefan Kochanek Rolf Marschalek |
| author_sort | Eric Kowarz |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T02:24:07Z |
| format | Article |
| id | doaj.art-30a61e87efa345b19c61d8c01cdaf176 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:24:07Z |
| publishDate | 2022-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-30a61e87efa345b19c61d8c01cdaf1762022-12-22T03:52:02ZengeLife Sciences Publications LtdeLife2050-084X2022-01-011110.7554/eLife.74974Vaccine-induced COVID-19 mimicry syndromeEric Kowarz0Lea Krutzke1https://orcid.org/0000-0002-4092-4131Marius Külp2Patrick Streb3Patrizia Larghero4Jennifer Reis5Silvia Bracharz6Tatjana Engler7Stefan Kochanek8Rolf Marschalek9https://orcid.org/0000-0003-4870-3445Institute of Pharmaceutical Biology/DCAL, Goethe-University of Frankfurt, Frankfurt am Main, GermanyDepartment of Gene Therapy, Ulm University, Ulm, GermanyInstitute of Pharmaceutical Biology/DCAL, Goethe-University of Frankfurt, Frankfurt am Main, GermanyInstitute of Pharmaceutical Biology/DCAL, Goethe-University of Frankfurt, Frankfurt am Main, GermanyInstitute of Pharmaceutical Biology/DCAL, Goethe-University of Frankfurt, Frankfurt am Main, GermanyInstitute of Pharmaceutical Biology/DCAL, Goethe-University of Frankfurt, Frankfurt am Main, GermanyInstitute of Pharmaceutical Biology/DCAL, Goethe-University of Frankfurt, Frankfurt am Main, GermanyDepartment of Gene Therapy, Ulm University, Ulm, GermanyDepartment of Gene Therapy, Ulm University, Ulm, GermanyInstitute of Pharmaceutical Biology/DCAL, Goethe-University of Frankfurt, Frankfurt am Main, GermanyTo 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.https://elifesciences.org/articles/74974SARS-CoV-2vaccinesRNAsplicingsplice variantsthrombosis |
| spellingShingle | Eric Kowarz Lea Krutzke Marius Külp Patrick Streb Patrizia Larghero Jennifer Reis Silvia Bracharz Tatjana Engler Stefan Kochanek Rolf Marschalek Vaccine-induced COVID-19 mimicry syndrome eLife SARS-CoV-2 vaccines RNA splicing splice variants thrombosis |
| 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 | SARS-CoV-2 vaccines RNA splicing splice variants thrombosis |
| url | https://elifesciences.org/articles/74974 |
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