What a fantastic read. The title might be a bit cryptic; the authors propose a convincing hypothesis that explains why Astrazeneca and JNJ vaccines cause rare but fatal blood clotting incidents.<p>TLDR: mRNA vaccines turn their payload into proteins in the cytosol.<p>Conversely, DNA vaccines (astrazeneca, JNJ) must first use the nucleus to turn their DNA into mRNA. This incurs so-called post-~translational~ (edit: post-transcriptional) modification to the genetic material prior to protein synthesis.<p>As it turns out, some of these unforseen modifications create soluble spike protein fragments that bind to epithelial cells. This in turn causes inflammatory, and coagulant, activity, which leads to the lethal side effects that are sometimes observed.
You know, my father in law had some kind of stroke about 2 weeks after his first shot. I thought maybe it was more than coincidence since there were reports of increased occurence of stroke with the virus. Hard to say if it's just coincidence or not, but this paper is making me wonder if it may have been an adverse event.<p>The really frustrating part is that most doctors don't report things like this to VAERS. How can we have good data to analyze and find correlations if most doctors do only the legal minimum reporting?! They are only requires to report the types of known adverse events listed in the packet insert. This doesn't help identify new types of adverse events. This is the second time in as many years that I've witnessed something that has the potential to be a rare but serious issue related to vaccines not be entered by the doctors. I had to report one myself, and it looks like this other one will simply go unreported.
TL;DR:<p>They have found first computationally then experimentally, a high number of potential splice sites in genetic code of AstraZeneca and J&J adeno viruses. This means instead of producing Spike protein, its shorter versions may be produced by cells infected with these adenoviruses. Those short proteins can cause rare sever side effects.<p>Quote: Here, we present first molecular evidence that vector-based vaccines encoding the Spike protein exhibit a problem that is completely absent in mRNA-based vaccines. This is due to the fact that during the vaccination step, the adenoviral DNA enters the nucleus and use the host machinery to transcribe its (trans)genes inside the nucleus. However, RNA viruses have evolved in the absence of any post-transcriptional modification systems that are usually enabled to process the primary RNA transcripts of nuclear encoded genes.<p>In this study, we experimentally validated our assumption that potential splice events cause the production of Spike protein variants that have lost the important membrane anchor, resulting in secreted, soluble Spike protein variants.
Just in case there are others out there who like me stumbled on the reference to 'codon optimized' in the abstract - here's a nice explanation:<p><a href="https://blog.addgene.org/to-codon-optimize-or-not-that-is-the-question" rel="nofollow">https://blog.addgene.org/to-codon-optimize-or-not-that-is-th...</a>
Has anybody similarly investigated the reports of cardiac inflammation following the administration of the mRNA vaccines, particularly the Pfizer one?<p>What explains that?
After my J&J shot, for weeks, my legs and feet would frequently feel “asleep.” Especially on waking but often during the day as well. The effect seems to have diminished (and I think mostly resolved) ~6 weeks later. No idea if it’s related to this.<p>(This is on top of the usual reaction of chills/fatigue the first night or two. I will say the fatigue seemed to go on for a while at some modestly higher than usual baseline but I can’t really quantify it or prove it. )
Does this only apply to the adenovirus vaccine or could this happen with the mRNA ones too?<p>It sounds like only the adenovirus, in which case the naming of the syndrome is… unfortunate in the middle of a stalling vaccine rollout. It will sow confusion I think.
What I want to know is if the transcription of the spike protein of the SARS-CoV-2 also leads to dangerous C-terminal truncated spike proteins or that SARS-CoV-2 transcription by definition doesn't lead to truncated spike proteins.
If so than catching SARS-CoV-2 is equally risky on this front.<p>From the abstract:<p>"..transcription of wildtype and codon-optimized Spike open reading frames enables alternative splice events that lead to C-terminal truncated, soluble Spike protein variants. These soluble Spike variants may initiate severe side effects when binding to ACE2-expressing endothelial cells in blood vessels"
Isn't it too be expected that when you train people's immune response by injecting mimicry spike proteins that people will react very similar to when they receive actual spike proteins?
I had reservations about J&J and AZ because of their complicated nature. I had more confidence in mRNA vaccines (Pfizer and Moderna) as simpler and more elegant to produce the desired immune response.<p>Anytime there are extra steps, there's added risks something can go wrong and cause unknown or horrible side-effects.
What a great example of ridiculousness of web 3.0
researchsquare.com loads and then "An unexpected error has occurred." fullscreen. Disabling JS and CSS makes it worse. So un-scientific.
Can anyone explain how long they expect this potential effect to last? The vaccine DNA presumably breaks down / dissipates after a period of time? And the spike protein fragments too? What might that period of time be?