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This involves testing the Omicron spike on a Wuhan-Hu-1 backbone. Damn near every single person in this comment thread has antibodies and T-cells to Omicron sp

This involves testing the Omicron spike on a Wuhan-Hu-1 backbone. Damn near every single person in this comment thread has antibodies and T-cells to Omicron spike and everyone naturally infected has T-cells for the original strain as well because T-cell epitopes aren't immune escape targets. Chances of this "escaping" the lab and producing another coronavirus wave are zero because that already happened. Like Derek Lowe pointed out nature already did a similar experiment with an Omicron spike and a Delta backbone because coronaviruses undergo recombination naturally: https://www.science.org/content/blog-post/gain-function-not-so-fast https://www.science.org/content/blog-post/gain-function-not-... Nobody has heard of the XD strain because there was so much immunity to it that it never really went anywhere.

tripletao 4y ago
> Chances of this "escaping" the lab and producing another coronavirus wave are zero because that already happened. Are you aware of any situation where the omicron spike and Wuhan backbone could have recombined naturally? As far as I know, the latter was extinct in the wild by the time the former emerged. It's good that the omicron/delta variant didn't blow up in humans. The omicron/Wuhan variant seems like another throw of the dice, though, and even a very small probability times millions of potential deaths is significant.
- lamontcg 4y ago
  You didn't read carefully what I wrote. The T-cell epitopes in all strains of SARS-CoV-2 are not subject to immune escape and there are thousands of them. Even the neutralizing antibodies to Wu-Hu-1 spike will cross react with omicron still. Nobody at this point is immune naive to this combination. And the most recent pandemic strain of SARS-CoV-2 was Omicron. If this Omicron spike containing virus escaped into the wild then it will encounter a human race with substantial neutralizing antibody activity to this exact spike protein sequence. And there isn't any "but maybe by splicing them together it literally changes everything, you can't possibly prove that isn't true" argument. This isn't science fiction. Inside the cell all of these proteins are diced up into small hexamers and displayed on MHC and it doesn't matter what the combination of the spike and the backbone are, the T-cell epitopes are going to be the same. Omicron spike will have Omicron antibody epitopes and Omicron T-cell epitopes, doen't matter what backbone you splice it onto. If you want to create a new pandemic, particularly one with "millions of potential deaths" you need to change this virus sufficiently that it is no longer identified as SARS-CoV-2 by our T-cells and you don't get that just by combining two different variants.
  - tripletao 4y ago
    If that's your argument, then what do you even need the XD strain for? You could simply assert that because natural omicron has spread widely, any lab chimera with the omicron spike must be safe. That seems remarkably cavalier though, considering that (a) natural omicron continues to spread, and kill people every day; and (b) while China's reported case counts are probably inaccurate, they probably do still have a large population that's completely omicron-naive.
    - lamontcg 4y ago
      I clearly didn't need the XD strain, I thought that would be read as supplementary. I routinely forget that no matter how clear your argument sounds to you that someone on the Internet will always misunderstand it (and pick apart a detail that has no central relevance).
      - tripletao 4y ago
        Except that natural omicron continues to kill people now? So it's empirically true that at least one backbone (i.e., the natural omicron backbone) plus the omicron spike remains able to cause significant sickness and death, despite the immunity we've built up, even outside China. So what's your argument that the risk from a different backbone is "zero"?
        lamontcg 4y ago
        Yet more misunderstanding. First of all they used BA.1 and that spike is nearly extinct and isn't causing much sickness and death, it has been out-competed by BA.5. BA.1 is literally "last years news" and BA.5 is immune evasive against BA.1. Any BA.1 spike is going to be recognized by the same neutralizing antibodies which has suppressed BA.1 circulation in the larger population. And I should have written something like the additional risk over the existing circulating pandemic strains is zero. It could cause infections and deaths, but just like XD it would be outcompeted quickly by BA.5 and wouldn't go anywhere, and the infected people would run exactly the same risk as they would have against the existing global pandemic. There is no way you get from this lab experiment to "COVID-22", it is still all the same virus, same pandemic, and a variant of the virus which will be substantially less fit against population immunity than BA.5 or whatever new variant winds up circulating this winter.
- Izkata 4y ago
  > As far as I know, the latter was extinct in the wild by the time the former emerged. Omicron isn't a descendant of Delta. It has an odd lineage that couldn't be explained and (unless new info has come up since I last looked) it was likely a descendant of either Wuhan or Alpha that mutated hidden from most of the world - one of the theories was that Wuhan/Alpha jumped to rats, then back to humans after becoming Omicron.
  - tripletao 4y ago
    I agree, but I don't think that's relevant? So I think my terminology was unclear. By "omicron/delta" I meant a recombinant of the omicron spike with the delta backbone, the one that apparently happened naturally and Derek Lowe describes as the XD strain. By "omicron/Wuhan" I meant a recombinant of the omicron spike with the Wuhan backbone, which these researchers created in their lab (and I don't believe had any opportunity to occur naturally, since the two lineages never existed simultaneously).
    - Izkata 4y ago
      > since the two lineages never existed simultaneously Some version of it would likely have existed in the rat-origin theory of Omicron as an intermediate stage, is what I meant.
      - tripletao 4y ago
        Ah, got it now. Then I guess the rats (or other cryptic hosts in which omicron evolved) might have been exposed to the omicron/Wuhan recombinant, but not humans.
Terr_ 4y ago
> Damn near every single person in this comment thread has antibodies and T-cells to Omicron spike and everyone naturally infected has T-cells for the original strain as well because T-cell epitopes aren't immune escape targets. Checking my layperson understanding by trying to make a dumbed-down version: "The outside of the new virus is stuff almost everybody's immune system should already be primed to seek and destroy, preferably before it hits a human cell. Even if it does hit a human cell, the inside stuff is old/simple enough that your immune system should easily recognize that the cell is infected and swollen, and kill it quickly too, there are no false everything-is-fine-here tricks."
- lamontcg 4y ago
  Correct. See for example: https://journals.asm.org/doi/10.1128/mbio.03617-21 https://journals.asm.org/doi/10.1128/mbio.03617-21 "These data suggest that virtually all individuals with existing anti-SARS-CoV-2 CD8+ T-cell responses should recognize the Omicron VOC and that SARS-CoV-2 has not evolved extensive T-cell escape mutations at this time." https://www.nature.com/articles/s41423-022-00838-5 https://www.nature.com/articles/s41423-022-00838-5 "Although the Omicron variant escapes neutralizing antibodies induced by COVID-19 vaccination or natural infection [1,2,3], our current analysis demonstrates that T cell epitopes are considerably conserved in the Omicron variant and that substantial proportions of memory T cells elicited by COVID-19 vaccination or natural infection respond to the Omicron spike. These results indicate that memory T cells may provide protective immunity during reinfection or breakthrough infection with the Omicron variant." Here's a review of all the SARS-CoV-2 T-cell epitopes: https://www.sciencedirect.com/science/article/pii/S1931312821002389 https://www.sciencedirect.com/science/article/pii/S193131282... "Here, we focus on a specific topic: our current knowledge concerning the definition and recognition of SARS-CoV-2-derived T cell epitopes in humans. While the data related to this topic was initially sparse, 25 different studies have now been published as of March 15, 2021 [...], which collectively report data from 1,197 human subjects (870 COVID-19 and 327 unexposed controls), leading to the identification of over 1,400 different CD4 (n = 382) and CD8 (n = 1052) T cell epitopes." And I'd highly recommend this video on the adaptive immune system, along with the whole rest of the series: https://www.youtube.com/watch?v=dXL2TvhNqZI&list=PLGhmZX2NKiNm0vqVhoYB_xZP6E6tGT6rU https://www.youtube.com/watch?v=dXL2TvhNqZI&list=PLGhmZX2NKi... (I think that covers how proteins get chopped up by proteases and then those short epitopes are displayed on MHC receptors and undifferentiated T-cells learn to identify them)

tripletao 4y ago

> Chances of this "escaping" the lab and producing another coronavirus wave are zero because that already happened. Are you aware of any situation where the omicron spike and Wuhan backbone could have recombined naturally? As far as I know, the latter was extinct in the wild by the time the former emerged. It's good that the omicron/delta variant didn't blow up in humans. The omicron/Wuhan variant seems like another throw of the dice, though, and even a very small probability times millions of potential deaths is significant.

lamontcg 4y ago
You didn't read carefully what I wrote. The T-cell epitopes in all strains of SARS-CoV-2 are not subject to immune escape and there are thousands of them. Even the neutralizing antibodies to Wu-Hu-1 spike will cross react with omicron still. Nobody at this point is immune naive to this combination. And the most recent pandemic strain of SARS-CoV-2 was Omicron. If this Omicron spike containing virus escaped into the wild then it will encounter a human race with substantial neutralizing antibody activity to this exact spike protein sequence. And there isn't any "but maybe by splicing them together it literally changes everything, you can't possibly prove that isn't true" argument. This isn't science fiction. Inside the cell all of these proteins are diced up into small hexamers and displayed on MHC and it doesn't matter what the combination of the spike and the backbone are, the T-cell epitopes are going to be the same. Omicron spike will have Omicron antibody epitopes and Omicron T-cell epitopes, doen't matter what backbone you splice it onto. If you want to create a new pandemic, particularly one with "millions of potential deaths" you need to change this virus sufficiently that it is no longer identified as SARS-CoV-2 by our T-cells and you don't get that just by combining two different variants.
- tripletao 4y ago
  If that's your argument, then what do you even need the XD strain for? You could simply assert that because natural omicron has spread widely, any lab chimera with the omicron spike must be safe. That seems remarkably cavalier though, considering that (a) natural omicron continues to spread, and kill people every day; and (b) while China's reported case counts are probably inaccurate, they probably do still have a large population that's completely omicron-naive.
  - lamontcg 4y ago
    I clearly didn't need the XD strain, I thought that would be read as supplementary. I routinely forget that no matter how clear your argument sounds to you that someone on the Internet will always misunderstand it (and pick apart a detail that has no central relevance).
    - tripletao 4y ago
      Except that natural omicron continues to kill people now? So it's empirically true that at least one backbone (i.e., the natural omicron backbone) plus the omicron spike remains able to cause significant sickness and death, despite the immunity we've built up, even outside China. So what's your argument that the risk from a different backbone is "zero"?
      - lamontcg 4y ago
        Yet more misunderstanding. First of all they used BA.1 and that spike is nearly extinct and isn't causing much sickness and death, it has been out-competed by BA.5. BA.1 is literally "last years news" and BA.5 is immune evasive against BA.1. Any BA.1 spike is going to be recognized by the same neutralizing antibodies which has suppressed BA.1 circulation in the larger population. And I should have written something like the additional risk over the existing circulating pandemic strains is zero. It could cause infections and deaths, but just like XD it would be outcompeted quickly by BA.5 and wouldn't go anywhere, and the infected people would run exactly the same risk as they would have against the existing global pandemic. There is no way you get from this lab experiment to "COVID-22", it is still all the same virus, same pandemic, and a variant of the virus which will be substantially less fit against population immunity than BA.5 or whatever new variant winds up circulating this winter.
Izkata 4y ago
> As far as I know, the latter was extinct in the wild by the time the former emerged. Omicron isn't a descendant of Delta. It has an odd lineage that couldn't be explained and (unless new info has come up since I last looked) it was likely a descendant of either Wuhan or Alpha that mutated hidden from most of the world - one of the theories was that Wuhan/Alpha jumped to rats, then back to humans after becoming Omicron.
- tripletao 4y ago
  I agree, but I don't think that's relevant? So I think my terminology was unclear. By "omicron/delta" I meant a recombinant of the omicron spike with the delta backbone, the one that apparently happened naturally and Derek Lowe describes as the XD strain. By "omicron/Wuhan" I meant a recombinant of the omicron spike with the Wuhan backbone, which these researchers created in their lab (and I don't believe had any opportunity to occur naturally, since the two lineages never existed simultaneously).
  - Izkata 4y ago
    > since the two lineages never existed simultaneously Some version of it would likely have existed in the rat-origin theory of Omicron as an intermediate stage, is what I meant.
    - tripletao 4y ago
      Ah, got it now. Then I guess the rats (or other cryptic hosts in which omicron evolved) might have been exposed to the omicron/Wuhan recombinant, but not humans.

Terr_ 4y ago

> Damn near every single person in this comment thread has antibodies and T-cells to Omicron spike and everyone naturally infected has T-cells for the original strain as well because T-cell epitopes aren't immune escape targets. Checking my layperson understanding by trying to make a dumbed-down version: "The outside of the new virus is stuff almost everybody's immune system should already be primed to seek and destroy, preferably before it hits a human cell. Even if it does hit a human cell, the inside stuff is old/simple enough that your immune system should easily recognize that the cell is infected and swollen, and kill it quickly too, there are no false everything-is-fine-here tricks."

lamontcg 4y ago
Correct. See for example: https://journals.asm.org/doi/10.1128/mbio.03617-21 https://journals.asm.org/doi/10.1128/mbio.03617-21 "These data suggest that virtually all individuals with existing anti-SARS-CoV-2 CD8+ T-cell responses should recognize the Omicron VOC and that SARS-CoV-2 has not evolved extensive T-cell escape mutations at this time." https://www.nature.com/articles/s41423-022-00838-5 https://www.nature.com/articles/s41423-022-00838-5 "Although the Omicron variant escapes neutralizing antibodies induced by COVID-19 vaccination or natural infection [1,2,3], our current analysis demonstrates that T cell epitopes are considerably conserved in the Omicron variant and that substantial proportions of memory T cells elicited by COVID-19 vaccination or natural infection respond to the Omicron spike. These results indicate that memory T cells may provide protective immunity during reinfection or breakthrough infection with the Omicron variant." Here's a review of all the SARS-CoV-2 T-cell epitopes: https://www.sciencedirect.com/science/article/pii/S1931312821002389 https://www.sciencedirect.com/science/article/pii/S193131282... "Here, we focus on a specific topic: our current knowledge concerning the definition and recognition of SARS-CoV-2-derived T cell epitopes in humans. While the data related to this topic was initially sparse, 25 different studies have now been published as of March 15, 2021 [...], which collectively report data from 1,197 human subjects (870 COVID-19 and 327 unexposed controls), leading to the identification of over 1,400 different CD4 (n = 382) and CD8 (n = 1052) T cell epitopes." And I'd highly recommend this video on the adaptive immune system, along with the whole rest of the series: https://www.youtube.com/watch?v=dXL2TvhNqZI&list=PLGhmZX2NKiNm0vqVhoYB_xZP6E6tGT6rU https://www.youtube.com/watch?v=dXL2TvhNqZI&list=PLGhmZX2NKi... (I think that covers how proteins get chopped up by proteases and then those short epitopes are displayed on MHC receptors and undifferentiated T-cells learn to identify them)