5 ms·

Well, thanks for attempting a numerical and physics based analysis. That's much more than you can find in the (public) documents submitted to regulators. I vote

Well, thanks for attempting a numerical and physics based analysis. That's much more than you can find in the (public) documents submitted to regulators. I voted you up as I've been looking for some sort of calculation for a long time. I have some questions though. Firstly, I think your analysis would only be true for Pfizer. Moderna has a dose 3x stronger (90mcg equivalent). Secondly, what exactly is the virus' immune evasion mechanism that the mRNA lacks? I thought it was the other way around - the mRNA is coded with pseudo-uridyl specifically to evade the immune system, but normal viral RNA doesn't use that trick. It would seem to be much more likely that the virus is detected by the immune system than the mRNA particles, specifically designed to evade it. For a novel argument like this one some citations would really be helpful. Where did you get the number of virions per infection, exactly? Surely this number will vary wildly between patients? What's the CI on that? Where did the 3x number come from? You say: "for each mRNA strand to produce 1000 spike proteins, which is very improbable." Why? From [1] we can read that each dose "consists of around 13,000 billion repetitions of the same 4284 characters". This seems like a huge number of repetitions of the spike protein sequence and this is a highly optimized sequence. They appeared to make great efforts to optimize it well beyond what nature would achieve. I'm not sure how to convert "strand" to "dose" here, but all your numbers and probabilities seem rather hypothetical. So what we're left with is still something much simpler and easier to measure (antibody levels), which are higher for vaccines, suggesting the body perceived it as a more aggressive invasion. And that's a problem: more antibodies = higher chance of autoimmune disease, at the very least. [1] https://berthub.eu/articles/posts/reverse-engineering-source-code-of-the-biontech-pfizer-vaccine/ https://berthub.eu/articles/posts/reverse-engineering-source...

sudosysgen 5y ago
> Why? From [1] we can read that each dose "consists of around 13,000 billion repetitions of the same 4284 characters". This seems like a huge number of repetitions of the spike protein sequence and this is a highly optimized sequence. They appeared to make great efforts to optimize it well beyond what nature would achieve. I'm not sure how to convert "strand" to "dose" here, but all your numbers and probabilities seem rather hypothetical Yes, each repetition is an mRNA strand, so what I wrote is in agreement with that quote. You would need each "repetition" to be translated to 1000+ spike proteins. Of course, the sequence is highly optimized, but it has to be optimized for many things - speed of translation and immunogenicity are much more important than persistence, and persistence is what would allow it to be translated many times. Least of which is because if you produce too many too fast the cell is just going to explode or form syncytiae. > Secondly, what exactly is the virus' immune evasion mechanism that the mRNA lacks? I thought it was the other way around - the mRNA is coded with pseudo-uridyl specifically to evade the immune system, but normal viral RNA doesn't use that trick. It would seem to be much more likely that the virus is detected by the immune system than the mRNA particles, specifically designed to evade it. Normal viral RNA is encapsulated in a virus. There is no need for pseudouridine because there won't be RNA in the open for the immune system to react until after infection. The vaccines need it because they want to create immune response to the spike instead of the mRNA and to lead to higher delivery. This, instead of leading to immune evasion, prevents the immune system from reacting to the wrong thing, which makes the vaccine more effective. See: (https://www.frontiersin.org/articles/10.3389/fcell.2021.789427/full https://www.frontiersin.org/articles/10.3389/fcell.2021.7894...) The immune evasion capability of the virus is completely different from pseudouridiliation, and are actually detrimental. It interferes with many signaling molecules necessary to the immune system, and induces the immune system to act as if it wasn't a virus but instead a parasite to some extent. This causes the immune system to react very inefficiently and erratically, causing responses that are damaging to the body, and also affects antibody formation. It can also induce T-cell exhaustion The virus also has more proteins than simply the S protein, which means that the immune system may initially focus on other parts of the virus. Then there is the fact that the lipid carrier as well as mRNA itself is highly immunogenic, even with pseudouridine. This means that for the same amount of spike protein, the vaccine will create a very strong and immediate immune reaction. https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8457632/ https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8457632/ The source for the number of virions is : https://www.pnas.org/content/118/25/e2024815118 https://www.pnas.org/content/118/25/e2024815118 I went with the higher estimates because Delta (and thus Omicron) have much higher viral loads. This is on the order of 1000x, but I only took 100x more than the lowe bound to be very conservative. If you want to be accurate, you can multiply the number of spike protein from the virus that I wrote by 100x : https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8375250/ https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8375250/ As you can see, it is normal that we would see a higher number of antibodies from the vaccine. > more antibodies = higher chance of autoimmune disease, at the very least. Absolutely not. What matters for autoimmune diseases isn't the amount of antibodies, but the type of antibodies. Vaccines only have one out of a dozen proteins in the vaccine and in only one conformation and one form, while the virus has all of those proteins in many conformations and will accumulate hundreds of mutations leading to even more antigens. So at the same amount of antibodies we expect a higher chance of autoantibodies from natural infection. As for why they didn't send this to regulators, why would they? They have empirical data from trials that show this didn't happen, and the regulators didn't ask for it. As for the 3x, viral assembly is a haphazard process. Virus proteins very often don't come together right - for some viruses the vast majority of virions are incomplete. I'm not aware of data on it for COVID except that the vast majority of virions that do have RNA (and not all do) are incomplete and can't infect, (see the number of virions paper), so for every RNA containing virion there is almost certainly much more than 3x as many spike proteins as if it was a complete virus. 3x is just a very conservative estimate. I hope you will appreciate this response!
- native_samples 5y ago
  I do appreciate the response a lot and I hope other readers who find this thread will do too, thanks for the effort!

sudosysgen 5y ago

> Why? From [1] we can read that each dose "consists of around 13,000 billion repetitions of the same 4284 characters". This seems like a huge number of repetitions of the spike protein sequence and this is a highly optimized sequence. They appeared to make great efforts to optimize it well beyond what nature would achieve. I'm not sure how to convert "strand" to "dose" here, but all your numbers and probabilities seem rather hypothetical Yes, each repetition is an mRNA strand, so what I wrote is in agreement with that quote. You would need each "repetition" to be translated to 1000+ spike proteins. Of course, the sequence is highly optimized, but it has to be optimized for many things - speed of translation and immunogenicity are much more important than persistence, and persistence is what would allow it to be translated many times. Least of which is because if you produce too many too fast the cell is just going to explode or form syncytiae. > Secondly, what exactly is the virus' immune evasion mechanism that the mRNA lacks? I thought it was the other way around - the mRNA is coded with pseudo-uridyl specifically to evade the immune system, but normal viral RNA doesn't use that trick. It would seem to be much more likely that the virus is detected by the immune system than the mRNA particles, specifically designed to evade it. Normal viral RNA is encapsulated in a virus. There is no need for pseudouridine because there won't be RNA in the open for the immune system to react until after infection. The vaccines need it because they want to create immune response to the spike instead of the mRNA and to lead to higher delivery. This, instead of leading to immune evasion, prevents the immune system from reacting to the wrong thing, which makes the vaccine more effective. See: (https://www.frontiersin.org/articles/10.3389/fcell.2021.789427/full https://www.frontiersin.org/articles/10.3389/fcell.2021.7894...) The immune evasion capability of the virus is completely different from pseudouridiliation, and are actually detrimental. It interferes with many signaling molecules necessary to the immune system, and induces the immune system to act as if it wasn't a virus but instead a parasite to some extent. This causes the immune system to react very inefficiently and erratically, causing responses that are damaging to the body, and also affects antibody formation. It can also induce T-cell exhaustion The virus also has more proteins than simply the S protein, which means that the immune system may initially focus on other parts of the virus. Then there is the fact that the lipid carrier as well as mRNA itself is highly immunogenic, even with pseudouridine. This means that for the same amount of spike protein, the vaccine will create a very strong and immediate immune reaction. https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8457632/ https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8457632/ The source for the number of virions is : https://www.pnas.org/content/118/25/e2024815118 https://www.pnas.org/content/118/25/e2024815118 I went with the higher estimates because Delta (and thus Omicron) have much higher viral loads. This is on the order of 1000x, but I only took 100x more than the lowe bound to be very conservative. If you want to be accurate, you can multiply the number of spike protein from the virus that I wrote by 100x : https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8375250/ https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8375250/ As you can see, it is normal that we would see a higher number of antibodies from the vaccine. > more antibodies = higher chance of autoimmune disease, at the very least. Absolutely not. What matters for autoimmune diseases isn't the amount of antibodies, but the type of antibodies. Vaccines only have one out of a dozen proteins in the vaccine and in only one conformation and one form, while the virus has all of those proteins in many conformations and will accumulate hundreds of mutations leading to even more antigens. So at the same amount of antibodies we expect a higher chance of autoantibodies from natural infection. As for why they didn't send this to regulators, why would they? They have empirical data from trials that show this didn't happen, and the regulators didn't ask for it. As for the 3x, viral assembly is a haphazard process. Virus proteins very often don't come together right - for some viruses the vast majority of virions are incomplete. I'm not aware of data on it for COVID except that the vast majority of virions that do have RNA (and not all do) are incomplete and can't infect, (see the number of virions paper), so for every RNA containing virion there is almost certainly much more than 3x as many spike proteins as if it was a complete virus. 3x is just a very conservative estimate. I hope you will appreciate this response!

native_samples 5y ago
I do appreciate the response a lot and I hope other readers who find this thread will do too, thanks for the effort!