Is the spike protein mRNA in Moderna & Pfizer vaccines identical to SARS-CoV-2 mRNA?

[Emily]

He's got a deep background in genetics.

https://www.youtube.com/watch?v=2-tMP_YM8Ds

M&M Clips: Is the spike protein mRNA in Moderna & Pfizer vaccines identical to SARS-CoV-2 mRNA?
Nick Jikomes
2.06K subscribers
Kevin McKernan talks to Nick about the differences between the mRNA found in the Pfizer and Moderna COVID vaccines compared to the mRNA found in the SARS-CoV-2. This particular mRNA sequence encodes the virus spike protein.

 

[Emily]

https://osf.io/bcsa6
McKernan, K., Kyriakopoulos, A. M., & McCullough, P. A. (2021, November 25). Differences in Vaccine and SARS-CoV-2 Replication Derived mRNA: Implications for Cell Biology and Future Disease. https://doi.org/10.31219/osf.io/bcsa6

Abstract

Codon optimization describes the process used to increase protein production by use of alternative but synonymous codon changes. In SARS-CoV-2 mRNA vaccines codon optimizations can result in differential secondary conformations that inevitably affect a protein’s function with significant consequences to the cell. Importantly, when codon optimization increases the GC content of synthetic mRNAs, there can be an inevitable enrichment of G-quartets which potentially form G-quadruplex structures. The emerging G-quadruplexes are favorable binding sites of RNA binding proteins like helicases that inevitably affect epigenetic reprogramming of the cell by altering transcription, translation and replication. In this study, we performed a RNAfold analysis to investigate alterations in secondary structures of mRNAs in SARS-CoV-2 vaccines due to codon optimization. We show a significant increase in the GC content of mRNAs in vaccines as compared to native SARS-CoV-2 RNA sequences encoding the spike protein. As the GC enrichment leads to more G-quadruplex structure formations, these may contribute to potential pathological processes initiated by SARS-CoV-2 molecular vaccination.

Supplemental Materials

osf.io/mfh6w/

Preprint DOI

10.31219/osf.io/bcsa6

License

CC-By Attribution 4.0 International

 

[JJackson]

While interesting academically this should not be taken as a concern relating to vaccination. The proof is in the pudding these vaccines have the best safety profile and the best vaccine efficacy, had they created a cause for concern this would have become evident in the phase 3 trials or post mass rollout. As the video explains the changes made were made for a good reason to improve in vivo speed and longevity so a decent quantity of Spike protein is made. Not discussed in the video there were also proline additions near the S2' cleavage site and other changes near the S1/S2 cleavage site to stabalise the conformational structure to increase the production of the most neutralising antibodies, these changes were also made in the J&J Ad vectored vaccine, but not AstraZeneca.

 

[sharon sanders]

bump this

 

[Emily]

Thanks, JJackson. I think the proline change to the vaccine spike is mentioned in the paper but not the details you have.
Do you know what the other changes made near the cleavage site are? I thought I read that one change was made in at least one of the mRNA vaccines to hopefully reduce chances of either ADE or autoimmune type side effects. I can't find any papers supporting that, though. Might just remember wrong.

 

[Emily]

New autoimmune disease. Maybe acceptable tradeoff risk for those susceptible to the virus if rare.

Acute autoimmune-like hepatitis with atypical anti-mitochondrial antibody after mRNA COVID-19 vaccination: A novel clinical entity?

 

[JJackson]

I do not know of any changes made for ADE or autoimmunity only so the spike shows a consistent conformation to elicit the most efficacious antibodies, plus the changes discussed to speed up translation in a mammalian host and to slow the host RNAase chopping up the mRNA before it can make enough spike.

 

[sharon sanders]

bump this