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Cause of issues with J&J and Astrazeneca vaccine found
Posted on: May 26, 2021 at 22:20:05 CT
TigerMatt STL
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mRNA tech is safer and more effective.
https://www.researchsquare.com/article/rs-558954/v1
What is the fundamental difference between mRNA and vector-based vaccines? The mRNA vaccines are delivered by a lipid nanoparticle containing the appropriate mRNA molecule - coding for the spike protein of SARS-CoV-2 - to muscle cells surrounding the injection site. Cells that have successfully taken up these nanoparticles will release their cargo mRNA into the cytosol, where it will be translated into Spike protein in the rough endoplasmatic reticulum (ER). Subsequently, the translated and folded Spike proteins will be post-translationally modified in the ER and Golgi apparatus and transported to the outer membrane - as membrane-anchored proteins. This way, the immune system is able to recognize the viral antigen, which in turn triggers the initial events for all subsequent immunological processes to produce specific B- and T- effector cells.
What happens to the same Spike gene when delivered via an adenoviral system? The adenovirus life cycle includes the infection of cells, uncoating of the virus in the cytosol, entry of the adenoviral DNA into the nucleus, and subsequently gene transcription by the host transcription machinery (6). All adenoviral systems follow exactly these steps (Ad5, Ad26 and chimp Ad). Thus, the SARS-CoV-2 Spike gene will be transcribed inside of the nucleus and subsequently exported as mRNA out of the nucleus. Arriving in the cytosol, the mRNA will again be translated into the Spike protein (see above).
And exactly here lies the problem: the viral piece of DNA - deriving from an RNA virus - is not optimized to be transcribed inside of the nucleus. Solely this 3,822 nucleotide long open reading frame, coding for a primary product of 1274 amino acid long Spike protein, contains 6 predicted splice donor and 5 predicted acceptor sites. This problem becomes even more severe when using codon-optimized Spike reading frames (depending on the company: up to 13 splice donor and 11 acceptor sites; see Fig. 1A). Thus, it could well be that the Spike open reading frame of SARS-CoV-2 is potentially disrupted by arbitrary splice events when transcribed inside the nucleus. 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.
Edited by TigerMatt at 22:21:55 on 05/26/21
https://www.researchsquare.com/article/rs-558954/v1
What is the fundamental difference between mRNA and vector-based vaccines? The mRNA vaccines are delivered by a lipid nanoparticle containing the appropriate mRNA molecule - coding for the spike protein of SARS-CoV-2 - to muscle cells surrounding the injection site. Cells that have successfully taken up these nanoparticles will release their cargo mRNA into the cytosol, where it will be translated into Spike protein in the rough endoplasmatic reticulum (ER). Subsequently, the translated and folded Spike proteins will be post-translationally modified in the ER and Golgi apparatus and transported to the outer membrane - as membrane-anchored proteins. This way, the immune system is able to recognize the viral antigen, which in turn triggers the initial events for all subsequent immunological processes to produce specific B- and T- effector cells.
What happens to the same Spike gene when delivered via an adenoviral system? The adenovirus life cycle includes the infection of cells, uncoating of the virus in the cytosol, entry of the adenoviral DNA into the nucleus, and subsequently gene transcription by the host transcription machinery (6). All adenoviral systems follow exactly these steps (Ad5, Ad26 and chimp Ad). Thus, the SARS-CoV-2 Spike gene will be transcribed inside of the nucleus and subsequently exported as mRNA out of the nucleus. Arriving in the cytosol, the mRNA will again be translated into the Spike protein (see above).
And exactly here lies the problem: the viral piece of DNA - deriving from an RNA virus - is not optimized to be transcribed inside of the nucleus. Solely this 3,822 nucleotide long open reading frame, coding for a primary product of 1274 amino acid long Spike protein, contains 6 predicted splice donor and 5 predicted acceptor sites. This problem becomes even more severe when using codon-optimized Spike reading frames (depending on the company: up to 13 splice donor and 11 acceptor sites; see Fig. 1A). Thus, it could well be that the Spike open reading frame of SARS-CoV-2 is potentially disrupted by arbitrary splice events when transcribed inside the nucleus. 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.
Edited by TigerMatt at 22:21:55 on 05/26/21
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Cause of issues with J&J and Astrazeneca vaccine found - TigerMatt STL - 5/26 22:20:05
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