VITT mechanism shows the way to avoid COVID-19 vaccine thrombotic reactions

German researchers have proposed a mechanism for the vaccine-induced thrombosis and thrombocytopenia (VITT) observed in a minority of people receiving the AstraZeneca and Johnson & Johnson COVID-19 vaccines.

The researchers said the fundamental difference between the mRNA and adenoviral vector-based vaccines was in their delivery to either the cytosol or nucleus.

“Most importantly, the RNA of this virus is translated and replicated only in the cytosol of infected cells, and thus, evolution of coronaviruses has always taken place in the cytosol of permissive cells, and in the absence of processes that are necessarily taking place when nuclear-encoded genes are being transcribed (capping, splicing and poly-adenylation).”

However in the case of the AZ and J&J vaccines, adenoviral DNA enters the nucleus of cells where it “is not optimised to be transcribed” and could result in arbitrary splice events.

“Most, if not all, of these undesirable splice events would produce shorter protein variants, disrupting the Spike protein upstream of the C-terminally located membrane anchor, and thus, leading to soluble Spike protein variants.”

In their research, yet to be peer reviewed, they presented the “first molecular evidence that vector-based vaccines encoding the Spike protein exhibit a problem that is completely absent in mRNA-based vaccines”.

They said the secreted, soluble Spike protein variants have been shown to cause strong inflammatory responses on endothelial cells.

“Soluble Spike variants together with newly built antibodies against Spike protein as well as the highly specific blood flow conditions in the central venous sinus of the brain may result in the rare but severe events after vaccination observed with ADZ1222/Vaxzevria,” the researchers said.

“Based on our findings, we strongly suggest that the Spike open reading frames – wildtype or codon-optimised – in vector-based vaccines has to be re-optimised to avoid unintended splice reactions and to increase the safety of these pharmaceutical products. “

They concluded that all mRNA-based vaccines should be safe products.

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