3 ms·

No traditional adjuvants is interesting, but I know the RNA is modified. It's not the exact mRNA spike protein. I believe they modify the amino acids to modulat

No traditional adjuvants is interesting, but I know the RNA is modified. It's not the exact mRNA spike protein. I believe they modify the amino acids to modulate immune reaction which may accomplish the same thing. The immune system doesn't like non-human RNA. Certain sequences, or even abundance of certain amino acids out of balance with human codes can set it off. Special RNA coding may be used in place of traditional adjuvants but much of it is proprietary at this point

mmmrtl 6y ago
You've kind of got it backwards. The RNA modifications (uracil depletion and using less immunogenic analogues) and in these vaccines are to avoid the getting too much immune response to the mRNA itself, and allow time for spike protein to be translated and lead to the immune response.
- throwaway189262 6y ago
  It could be both. The goal is to evade the innate extracellular immune system while priming adaptive immunity. I don't think we know enough about their RNA modifications to say they put all their focus on one instead of the other. Traditionally, mRNA vaccines were not very effective. There's definitely some magic "trade secret" sauce in these vaccines.
  - mmmrtl 6y ago
    I can tell you for sure that the amino acid content isn't changed in any obscure way - it's exactly the original Wuhan genome's spike protein, with two proline mutations that put it in a prefusion conformation that makes a more stable target for antibodies, a strategy developed in research for SARS/MERS vaccines. The codons and overall RNA sequence are heavily optimized in ways that outsiders and I suspect they companies themselves don't really understand. Pfizer's production version of BNT162b2 is actually BNT162b2 V9, suggesting they tried combinations of many different strategies and took the one that worked the best. You could be right that some of the optimizations had immune effects that no one knows or understands yet, but I doubt there was real intention behind it. Magic sauce indeed! The sequence is actually public, but as far as I know no one has figured out what optimizations worked in the end aside from the uracil-depletion + 1-methylpseudouridine trick to avoid an immune response to what looks like viral RNA. https://mednet-communities.net/inn/db/media/docs/11889.doc https://mednet-communities.net/inn/db/media/docs/11889.doc

mmmrtl 6y ago

You've kind of got it backwards. The RNA modifications (uracil depletion and using less immunogenic analogues) and in these vaccines are to avoid the getting too much immune response to the mRNA itself, and allow time for spike protein to be translated and lead to the immune response.

throwaway189262 6y ago
It could be both. The goal is to evade the innate extracellular immune system while priming adaptive immunity. I don't think we know enough about their RNA modifications to say they put all their focus on one instead of the other. Traditionally, mRNA vaccines were not very effective. There's definitely some magic "trade secret" sauce in these vaccines.
- mmmrtl 6y ago
  I can tell you for sure that the amino acid content isn't changed in any obscure way - it's exactly the original Wuhan genome's spike protein, with two proline mutations that put it in a prefusion conformation that makes a more stable target for antibodies, a strategy developed in research for SARS/MERS vaccines. The codons and overall RNA sequence are heavily optimized in ways that outsiders and I suspect they companies themselves don't really understand. Pfizer's production version of BNT162b2 is actually BNT162b2 V9, suggesting they tried combinations of many different strategies and took the one that worked the best. You could be right that some of the optimizations had immune effects that no one knows or understands yet, but I doubt there was real intention behind it. Magic sauce indeed! The sequence is actually public, but as far as I know no one has figured out what optimizations worked in the end aside from the uracil-depletion + 1-methylpseudouridine trick to avoid an immune response to what looks like viral RNA. https://mednet-communities.net/inn/db/media/docs/11889.doc https://mednet-communities.net/inn/db/media/docs/11889.doc