Vaccine-induced COVID-19 mimicry syndrome.
Vaccine-induced COVID-19 mimicry syndrome.
复制标题
疫苗诱导的covid-19模拟综合征。
DOI：
10.7554/elife.74974
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发表时间：
2022-01-27
期刊：
影响因子：
7.7
通讯作者：
Marschalek R
中科院分区：
文献类型：
--
作者：
Kowarz E;Krutzke L;Külp M;Streb P;Larghero P;Reis J;Bracharz S;Engler T;Kochanek S;Marschalek R
为了对抗由RNA病毒SARS-CoV-2引起的COVID-19大流行，全球疫苗接种运动正在进行中，以实现主要使用基于腺病毒载体或mRNA的疫苗对数十亿人进行免疫接种，所有疫苗都编码SARS-CoV-2刺突蛋白。在一些罕见的病例中，脑静脉窦血栓形成（CVST）被报告为首次接种后4-14天发生的严重副作用，通常伴有血小板减少症。除CVST外，还观察到内脏静脉血栓形成（SVT）和其他血栓栓塞事件。这些事件仅在接种基于腺病毒载体的疫苗后发生，而在接种基于mRNA的疫苗后未发生。与此同时，科学家们提出了一种基于免疫的病理机制，这种情况被称为疫苗诱导的免疫血栓性血小板减少症（VITT）。在这里，我们描述了一个意想不到的机制，可以解释血栓栓塞事件发生与DNA为基础的，而不是与RNA为基础的疫苗。我们表明，DNA编码的刺突蛋白编码的mRNA可以剪接的方式，刺突的跨膜锚丢失，使几乎全长刺突是从细胞分泌。当通过ACE 2受体与细胞结合时，分泌的刺突变体可能引发严重的副作用。避免这种剪接事件应该成为合理疫苗设计的一部分，以提高预期疫苗的安全性。
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.