4 ms·

This is a false assumption as they have different mRNA instructions. As you point out, wait until there is data and treat the vaccines independently.

flobosg 5y ago
> This is a false assumption as they have different mRNA instructions Depending on what you mean by “mRNA instructions” that might not be the case. Both vaccine mRNAs encode exactly the same variant of the spike protein.
- rantwasp 5y ago
  yes, but no. while it’s technically the same protein, the way it was optimized differs (not by much but it’s different). the vaccine itself has the instructions to produce something that resembles the spike protein (to which your immune system goes in overdrive and generates antibodies)
  - flobosg 5y ago
    > while it’s technically the same protein Not technically, it’s actually the same protein/polypeptide sequence in both cases, 100% identical, including the proline mutations that stabilize the prefusion conformation. You can check that easily by translating and aligning in silico both coding RNA sequences. > the way it was optimized differs (not by much but it’s different) I’m assuming that you’re referring to the codon optimization step that the RNA sequences underwent. While both coding sequences were optimized differently, this has no effect on the final protein product.
    - dharma1 5y ago
      Does this mean you can mix the two vaccines - ie. take two shots of moderna, and a later in the year a booster shot of (updated) Pfizer/BnT? So far I haven’t seen conclusive information about mixing the vaccines, but I think that will be the reality for booster shots late this year/early next year in the UK.
      - flobosg 5y ago
        While the spike protein is the same, there are differences in the overall formulation and delivery system. An additional booster shot from a different mRNA vaccine should be safe, but still needs to be evaluated. I wouldn’t be surprised if trials are already underway.
      - johnchristopher 5y ago
        I remember reading they had a different something on the scale of ten in the recipe though.
      - takeda 5y ago
        My understanding is that the reason it was required to have the same first and second dose was to make it easier tracing if there was a problem with a particular vaccine and to get the efficacy numbers manufacturers were promising. From what I heard, in normal circumstances is even recommend to give a booster vaccine shot from a different manufacturer.
    - rantwasp 5y ago
      here. do the diff yourself: https://github.com/NAalytics/Assemblies-of-putative-SARS-CoV2-spike-encoding-mRNA-sequences-for-vaccines-BNT-162b2-and-mRNA-1273/blob/main/Figure1Figure2_032321.fasta https://github.com/NAalytics/Assemblies-of-putative-SARS-CoV... I’m not gonna go into how the virus was sequenced or what the process to generate the vaccine was, but in this case, I believe your claim of being 100% identical is wrong.
      - flobosg 5y ago
        Please read carefully my previous post. Protein sequence != RNA sequence. I already stated that both coding RNA sequences are different. It is their product, the protein sequence, that is 100% identical in both sequence and structure. The protein that, as you mentioned, is presented as an antigen to the immune system. If you don’t believe me, and since you already found the FASTA mRNA sequence (or, more specifically, its cDNA equivalent) for both vaccines, you can translate[1] each spike protein RNA section and then align[2] both translated protein sequences. This is what you get: #======================================= # # Aligned_sequences: 2 # 1: Pfizer # 2: Moderna # Matrix: EBLOSUM62 # Gap_penalty: 10.0 # Extend_penalty: 0.5 # # Length: 1273 # Identity: 1273/1273 (100.0%) # Similarity: 1273/1273 (100.0%) # Gaps: 0/1273 ( 0.0%) # Score: 6727.0 # # #======================================= Pfizer 1 MFVFLVLLPLVSSQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHS 50 |||||||||||||||||||||||||||||||||||||||||||||||||| Moderna 1 MFVFLVLLPLVSSQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHS 50 Pfizer 51 TQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNI 100 |||||||||||||||||||||||||||||||||||||||||||||||||| Moderna 51 TQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNI 100 ... Pfizer 1201 QELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSC 1250 |||||||||||||||||||||||||||||||||||||||||||||||||| Moderna 1201 QELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSC 1250 Pfizer 1251 GSCCKFDEDDSEPVLKGVKLHYT 1273 ||||||||||||||||||||||| Moderna 1251 GSCCKFDEDDSEPVLKGVKLHYT 1273 [1]: https://web.expasy.org/translate/ https://web.expasy.org/translate/ [2]: https://www.ebi.ac.uk/Tools/psa/emboss_needle/ https://www.ebi.ac.uk/Tools/psa/emboss_needle/
        5y ago
fastball 5y ago
The overall mRNA is different due to different signal peptides, untranslated regions (UTR), etc. But the mRNA sequence that encodes the spike protein is identical, and presumably that is what would give resistance to variants.
- flobosg 5y ago
  A nitpick: signal peptides are also the same.

flobosg 5y ago

> This is a false assumption as they have different mRNA instructions Depending on what you mean by “mRNA instructions” that might not be the case. Both vaccine mRNAs encode exactly the same variant of the spike protein.

rantwasp 5y ago
yes, but no. while it’s technically the same protein, the way it was optimized differs (not by much but it’s different). the vaccine itself has the instructions to produce something that resembles the spike protein (to which your immune system goes in overdrive and generates antibodies)
- flobosg 5y ago
  > while it’s technically the same protein Not technically, it’s actually the same protein/polypeptide sequence in both cases, 100% identical, including the proline mutations that stabilize the prefusion conformation. You can check that easily by translating and aligning in silico both coding RNA sequences. > the way it was optimized differs (not by much but it’s different) I’m assuming that you’re referring to the codon optimization step that the RNA sequences underwent. While both coding sequences were optimized differently, this has no effect on the final protein product.
  - dharma1 5y ago
    Does this mean you can mix the two vaccines - ie. take two shots of moderna, and a later in the year a booster shot of (updated) Pfizer/BnT? So far I haven’t seen conclusive information about mixing the vaccines, but I think that will be the reality for booster shots late this year/early next year in the UK.
    - flobosg 5y ago
      While the spike protein is the same, there are differences in the overall formulation and delivery system. An additional booster shot from a different mRNA vaccine should be safe, but still needs to be evaluated. I wouldn’t be surprised if trials are already underway.
    - johnchristopher 5y ago
      I remember reading they had a different something on the scale of ten in the recipe though.
    - takeda 5y ago
      My understanding is that the reason it was required to have the same first and second dose was to make it easier tracing if there was a problem with a particular vaccine and to get the efficacy numbers manufacturers were promising. From what I heard, in normal circumstances is even recommend to give a booster vaccine shot from a different manufacturer.
  - rantwasp 5y ago
    here. do the diff yourself: https://github.com/NAalytics/Assemblies-of-putative-SARS-CoV2-spike-encoding-mRNA-sequences-for-vaccines-BNT-162b2-and-mRNA-1273/blob/main/Figure1Figure2_032321.fasta https://github.com/NAalytics/Assemblies-of-putative-SARS-CoV... I’m not gonna go into how the virus was sequenced or what the process to generate the vaccine was, but in this case, I believe your claim of being 100% identical is wrong.
    - flobosg 5y ago
      Please read carefully my previous post. Protein sequence != RNA sequence. I already stated that both coding RNA sequences are different. It is their product, the protein sequence, that is 100% identical in both sequence and structure. The protein that, as you mentioned, is presented as an antigen to the immune system. If you don’t believe me, and since you already found the FASTA mRNA sequence (or, more specifically, its cDNA equivalent) for both vaccines, you can translate[1] each spike protein RNA section and then align[2] both translated protein sequences. This is what you get: #======================================= # # Aligned_sequences: 2 # 1: Pfizer # 2: Moderna # Matrix: EBLOSUM62 # Gap_penalty: 10.0 # Extend_penalty: 0.5 # # Length: 1273 # Identity: 1273/1273 (100.0%) # Similarity: 1273/1273 (100.0%) # Gaps: 0/1273 ( 0.0%) # Score: 6727.0 # # #======================================= Pfizer 1 MFVFLVLLPLVSSQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHS 50 |||||||||||||||||||||||||||||||||||||||||||||||||| Moderna 1 MFVFLVLLPLVSSQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHS 50 Pfizer 51 TQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNI 100 |||||||||||||||||||||||||||||||||||||||||||||||||| Moderna 51 TQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNI 100 ... Pfizer 1201 QELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSC 1250 |||||||||||||||||||||||||||||||||||||||||||||||||| Moderna 1201 QELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSC 1250 Pfizer 1251 GSCCKFDEDDSEPVLKGVKLHYT 1273 ||||||||||||||||||||||| Moderna 1251 GSCCKFDEDDSEPVLKGVKLHYT 1273 [1]: https://web.expasy.org/translate/ https://web.expasy.org/translate/ [2]: https://www.ebi.ac.uk/Tools/psa/emboss_needle/ https://www.ebi.ac.uk/Tools/psa/emboss_needle/
      - 5y ago

fastball 5y ago

The overall mRNA is different due to different signal peptides, untranslated regions (UTR), etc. But the mRNA sequence that encodes the spike protein is identical, and presumably that is what would give resistance to variants.

flobosg 5y ago
A nitpick: signal peptides are also the same.