5 ms·

SARS-CoV-2 immune evasion by the B.1.427/B.1.429 variant of concern

27 points by guybedo 5y ago

josefdlange 5y ago
Quick -- someone with epidemiology/virology experience -- can we get a summarization for the layman? How concerning is the concern noted in the title?
- scrollaway 5y ago
  "Variant of concern" is just a CDC classification which applies to all variants which are interesting enough to require close monitoring, for whatever reason. It is below "variant of high consequence" in the ladder of how worried you should be. https://www.cdc.gov/coronavirus/2019-ncov/variants/variant-info.html https://www.cdc.gov/coronavirus/2019-ncov/variants/variant-i...
  - SheinhardtWigCo 5y ago
    Even Delta is not a "variant of high consequence". There will be extreme reluctance to make that declaration because it would signal that lockdowns and other non-pharmaceutical interventions will be needed for a much longer period than we previously thought.
    - GekkePrutser 5y ago
      The WHO is way too political. They could have stopped it right at the start by (advising to) quarantining China from the rest of the world but they decided to play along with China that played down the seriousness (remember that doctor that was being punished by China for revealing the truth). We're still cleaning up their mess. Then with India and the Delta variant the same things happened. https://www.cp24.com/mobile/world/india-was-warned-of-delta-covid-19-variant-risks-in-early-march-failed-to-heed-warnings-1.5470630 https://www.cp24.com/mobile/world/india-was-warned-of-delta-... The WHO should be about science not politics. If it's that dangerous they should declare it as such so appropriate measures can be taken. All these things were known in advance but measures not taken because of political or economic concerns.
      - dragonwriter 5y ago
        > They could have stopped it right at the start by quarantining China from the rest of the world No, they couldn't. For one thing, WHO doesn't regulate international travel and couldn't quarantine anyone if they wanted to. (Now, various governments—including the US government which had intelligence on it before China announced anything publicly—could have stopped travel from China, but that's...not the WHO.)
        GekkePrutser 5y ago
        No they don't regulate international travel but they could have publicly come out and said this would have been necessary. Any government sidestepping them would have taken a huge political risk if they had been wrong (and they would have been!). It's a big thing for a government to overrule the WHO. I'm sure that they would have done it if they had been about science and not about politics. All the knowledge of how serious this was, was there at the start. I think the discussion of how it came to spread worldwide is even more important than how it emerged in the first place. In particular because we keep making the same mistakes with these variants. The failure to contain the British (Alpha) variant should have been enough warning to up that game. If Delta hadn't spread to Europe and US we would have been in a great situation with current vaccination levels because Alpha was not that dangerous after all. I'm just worried we will make the wrong choices again for the next one which may be even more destructive. For Delta we're too late. For whatever is next we may not be.
        vagrantJin 5y ago
        I think you overestimate how well the WHO is run. It has to be political because it is a multinational political entity whether they call themselves that or not. They don't have willy nilly use of their funding either, and they sometimes have to deal with very difficult heads of state. It's to be expected for an organisation that big, with that size scope to be in a state of semi-chaos no different than a huge multinational.
        GekkePrutser 5y ago
    - scrollaway 5y ago
      If you use the High consequence classification for delta, what do you use when we're truly fucked? Delta isn't vaccine resistant and isn't significantly more deadly. Sure it spreads a lot more but most countries are dealing with it just fine. There probably needs to be a fourth classification between HOC and HOIC but whatever, it doesn't really matter.
  - deleted 5y ago
    [deleted]
- m0llusk 5y ago
  Antibodies generated as a response to vaccination that target the SARS-CoV2 binding domain, which is what makes the initial bond with an ACE2 receptor to enter a cell and begin infection, are less effective against some variants that have a modified binding domain. Rather than addressing relative risks, this paper is more about understanding the mechanisms involved which appear to be a combination of modifications to the structure of the binding domain and rearrangement of its disulfide bonds.
laGrenouille 5y ago
This variant (better known as the epsilon variant) is no longer even classifed as a variant of concern by the WHO [1]. It seems that was likely because it is being dominated by the delta variant. [1] https://www.who.int/en/activities/tracking-SARS-CoV-2-variants/ https://www.who.int/en/activities/tracking-SARS-CoV-2-varian...
- rasengan0 5y ago
  +1 Indeed, accounted for back mid June 2021: delta > epsilon (west coast variant): https://youtu.be/xR-LbraMlgs?t=706 https://youtu.be/xR-LbraMlgs?t=706
criticaltinker 5y ago
From the article: "The acquisition of the L452R substitution by multiple lineages across multiple continents, including the B.1.617.1 and B.1.617.2 lineages emerging in India, is suggestive of positive selection, which might result from the selective pressure of RBD-specific neutralizing Abs" This is another incremental yet damning piece of evidence suggesting that vaccine induced selective pressure is enhancing the fitness of these variants of concern. There is growing evidence throughout the peer-reviewed literature suggesting that immune escape is a valid concern [1][2][3][4]. Excerpts from [1]: - "The spike protein receptor-binding domain (RBD) of SARS-CoV-2 is the molecular target for many vaccines and antibody-based prophylactics aimed at bringing COVID-19 under control." - "Such a narrow molecular focus raises the specter of viral immune evasion as a potential failure mode for these biomedical interventions. With the emergence of new strains of SARS-CoV-2 with altered transmissibility and immune evasion potential, a critical question is this: how easily can the virus escape neutralizing antibodies (nAbs) targeting the spike RBD?" - "Our modeling suggests that SARS-CoV-2 mutants with one or two mildly deleterious mutations are expected to exist in high numbers due to neutral genetic variation, and consequently resistance to vaccines or other prophylactics that rely on one or two antibodies for protection can develop quickly -and repeatedly- under positive selection." - "The speed at which nAb resistance develops in the population increases substantially as the number of infected individuals increases, suggesting that complementary strategies to prevent SARS-CoV-2 transmission that exert specific pressure on other proteins (e.g., antiviral prophylactics) or that do not exert a specific selective pressure on the virus (e.g., high-efficiency air filtration, masking, ultraviolet air purification) are key to reducing the risk of immune escape" - "Strategies for viral elimination should therefore be diversified across molecular targets and therapeutic modalities" [1] Risk of rapid evolutionary escape from biomedical interventions targeting SARS-CoV-2 spike protein (April 2021) https://pubmed.ncbi.nlm.nih.gov/33909660/ https://pubmed.ncbi.nlm.nih.gov/33909660/ [2] Why does drug resistance readily evolve but vaccine resistance does not? (2017) https://royalsocietypublishing.org/doi/pdf/10.1098/rspb.2016.2562 https://royalsocietypublishing.org/doi/pdf/10.1098/rspb.2016... [3] Imperfect Vaccination Can Enhance the Transmission of Highly Virulent Pathogens (2015) https://journals.plos.org/plosbiology/article?id=10.1371%2Fjournal.pbio.1002198 https://journals.plos.org/plosbiology/article?id=10.1371%2Fj... [4] The adaptive evolution of virulence: a review of theoretical predictions and empirical tests (2015) https://www.cambridge.org/core/services/aop-cambridge-core/content/view/30EC8AB1717BF7A173CF5E051DBB498F/S003118201500092Xa_hi.pdf/_div_class__title__The_adaptive_evolution_of_virulence__a_review_of_theoretical_predictions_and_empirical_tests__div_.pdf https://www.cambridge.org/core/services/aop-cambridge-core/c...

27 points by guybedo 5y ago

Quick -- someone with epidemiology/virology experience -- can we get a summarization for the layman? How concerning is the concern noted in the title?

scrollaway 5y ago
"Variant of concern" is just a CDC classification which applies to all variants which are interesting enough to require close monitoring, for whatever reason. It is below "variant of high consequence" in the ladder of how worried you should be. https://www.cdc.gov/coronavirus/2019-ncov/variants/variant-info.html https://www.cdc.gov/coronavirus/2019-ncov/variants/variant-i...
- SheinhardtWigCo 5y ago
  Even Delta is not a "variant of high consequence". There will be extreme reluctance to make that declaration because it would signal that lockdowns and other non-pharmaceutical interventions will be needed for a much longer period than we previously thought.
  - GekkePrutser 5y ago
    The WHO is way too political. They could have stopped it right at the start by (advising to) quarantining China from the rest of the world but they decided to play along with China that played down the seriousness (remember that doctor that was being punished by China for revealing the truth). We're still cleaning up their mess. Then with India and the Delta variant the same things happened. https://www.cp24.com/mobile/world/india-was-warned-of-delta-covid-19-variant-risks-in-early-march-failed-to-heed-warnings-1.5470630 https://www.cp24.com/mobile/world/india-was-warned-of-delta-... The WHO should be about science not politics. If it's that dangerous they should declare it as such so appropriate measures can be taken. All these things were known in advance but measures not taken because of political or economic concerns.
    - dragonwriter 5y ago
      > They could have stopped it right at the start by quarantining China from the rest of the world No, they couldn't. For one thing, WHO doesn't regulate international travel and couldn't quarantine anyone if they wanted to. (Now, various governments—including the US government which had intelligence on it before China announced anything publicly—could have stopped travel from China, but that's...not the WHO.)
      - GekkePrutser 5y ago
        No they don't regulate international travel but they could have publicly come out and said this would have been necessary. Any government sidestepping them would have taken a huge political risk if they had been wrong (and they would have been!). It's a big thing for a government to overrule the WHO. I'm sure that they would have done it if they had been about science and not about politics. All the knowledge of how serious this was, was there at the start. I think the discussion of how it came to spread worldwide is even more important than how it emerged in the first place. In particular because we keep making the same mistakes with these variants. The failure to contain the British (Alpha) variant should have been enough warning to up that game. If Delta hadn't spread to Europe and US we would have been in a great situation with current vaccination levels because Alpha was not that dangerous after all. I'm just worried we will make the wrong choices again for the next one which may be even more destructive. For Delta we're too late. For whatever is next we may not be.
        vagrantJin 5y ago
        I think you overestimate how well the WHO is run. It has to be political because it is a multinational political entity whether they call themselves that or not. They don't have willy nilly use of their funding either, and they sometimes have to deal with very difficult heads of state. It's to be expected for an organisation that big, with that size scope to be in a state of semi-chaos no different than a huge multinational.
        GekkePrutser 5y ago
  - scrollaway 5y ago
    If you use the High consequence classification for delta, what do you use when we're truly fucked? Delta isn't vaccine resistant and isn't significantly more deadly. Sure it spreads a lot more but most countries are dealing with it just fine. There probably needs to be a fourth classification between HOC and HOIC but whatever, it doesn't really matter.
- deleted 5y ago
  [deleted]
m0llusk 5y ago
Antibodies generated as a response to vaccination that target the SARS-CoV2 binding domain, which is what makes the initial bond with an ACE2 receptor to enter a cell and begin infection, are less effective against some variants that have a modified binding domain. Rather than addressing relative risks, this paper is more about understanding the mechanisms involved which appear to be a combination of modifications to the structure of the binding domain and rearrangement of its disulfide bonds.

laGrenouille 5y ago

This variant (better known as the epsilon variant) is no longer even classifed as a variant of concern by the WHO [1]. It seems that was likely because it is being dominated by the delta variant. [1] https://www.who.int/en/activities/tracking-SARS-CoV-2-variants/ https://www.who.int/en/activities/tracking-SARS-CoV-2-varian...

rasengan0 5y ago
+1 Indeed, accounted for back mid June 2021: delta > epsilon (west coast variant): https://youtu.be/xR-LbraMlgs?t=706 https://youtu.be/xR-LbraMlgs?t=706

criticaltinker 5y ago

From the article: "The acquisition of the L452R substitution by multiple lineages across multiple continents, including the B.1.617.1 and B.1.617.2 lineages emerging in India, is suggestive of positive selection, which might result from the selective pressure of RBD-specific neutralizing Abs" This is another incremental yet damning piece of evidence suggesting that vaccine induced selective pressure is enhancing the fitness of these variants of concern. There is growing evidence throughout the peer-reviewed literature suggesting that immune escape is a valid concern [1][2][3][4]. Excerpts from [1]: - "The spike protein receptor-binding domain (RBD) of SARS-CoV-2 is the molecular target for many vaccines and antibody-based prophylactics aimed at bringing COVID-19 under control." - "Such a narrow molecular focus raises the specter of viral immune evasion as a potential failure mode for these biomedical interventions. With the emergence of new strains of SARS-CoV-2 with altered transmissibility and immune evasion potential, a critical question is this: how easily can the virus escape neutralizing antibodies (nAbs) targeting the spike RBD?" - "Our modeling suggests that SARS-CoV-2 mutants with one or two mildly deleterious mutations are expected to exist in high numbers due to neutral genetic variation, and consequently resistance to vaccines or other prophylactics that rely on one or two antibodies for protection can develop quickly -and repeatedly- under positive selection." - "The speed at which nAb resistance develops in the population increases substantially as the number of infected individuals increases, suggesting that complementary strategies to prevent SARS-CoV-2 transmission that exert specific pressure on other proteins (e.g., antiviral prophylactics) or that do not exert a specific selective pressure on the virus (e.g., high-efficiency air filtration, masking, ultraviolet air purification) are key to reducing the risk of immune escape" - "Strategies for viral elimination should therefore be diversified across molecular targets and therapeutic modalities" [1] Risk of rapid evolutionary escape from biomedical interventions targeting SARS-CoV-2 spike protein (April 2021) https://pubmed.ncbi.nlm.nih.gov/33909660/ https://pubmed.ncbi.nlm.nih.gov/33909660/ [2] Why does drug resistance readily evolve but vaccine resistance does not? (2017) https://royalsocietypublishing.org/doi/pdf/10.1098/rspb.2016.2562 https://royalsocietypublishing.org/doi/pdf/10.1098/rspb.2016... [3] Imperfect Vaccination Can Enhance the Transmission of Highly Virulent Pathogens (2015) https://journals.plos.org/plosbiology/article?id=10.1371%2Fjournal.pbio.1002198 https://journals.plos.org/plosbiology/article?id=10.1371%2Fj... [4] The adaptive evolution of virulence: a review of theoretical predictions and empirical tests (2015) https://www.cambridge.org/core/services/aop-cambridge-core/content/view/30EC8AB1717BF7A173CF5E051DBB498F/S003118201500092Xa_hi.pdf/_div_class__title__The_adaptive_evolution_of_virulence__a_review_of_theoretical_predictions_and_empirical_tests__div_.pdf https://www.cambridge.org/core/services/aop-cambridge-core/c...