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Slack / Private Message Drop, p.400 [SLACK_000614] · slack_pm:msg:04133

Page text: p.400 · original PDF

Date
2021-01-14 16:31
Type
chat message · slack
mentioned
Robert F. Garry
recipient
Robert F. Garry, Edward C. Holmes, Andrew Rambaut
speaker
Kristian G. Andersen

Recipients on this medium are inferred from channel membership, not per-message addressing.

Tangential to this, but important to fully understand just how tolerant SARS-CoV-2 is to mutations in immunologicallykey sites - HCoV-NL63 uses ACE2 as a receptor too and is very diverged from SC2. @Robert Garry - I don't know ifyou have looked more closely at that virus going through your alignments / structures?

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  1. 2021-01-14 16:24 Kristian G. Andersen open
    Yeah, going to be really important over the next couple of months to understand what's going on here. The immunologists seem very (VERY!) sure there is no problem with the UK/RSA/Brazil lineages when it comes to immunity. I'm less certain.
  2. 2021-01-14 16:26 Andrew Rambaut open
    I agree. If these constellations have no effect on vaccine elicited immunity then boy will we have dodged a bullet.
  3. 2021-01-14 16:27 Kristian G. Andersen open
    I'm almost certain they'll have _some_ effect on efficacy, but just not sure how much. Let's hope very little (say, 95%> 92%...)
  4. 2021-01-14 16:27 Kristian G. Andersen open
    Lord knows what the effectiveness is going to be anyway. We'll see...
  5. 2021-01-14 16:31 Kristian G. Andersen
    Tangential to this, but important to fully understand just how tolerant SARS-CoV-2 is to mutations in immunologicallykey sites - HCoV-NL63 uses ACE2 as a receptor too and is very diverged from SC2. @Robert Garry - I don't know ifyou have looked more closely at that virus going through your alignments / structures?
  6. 2021-01-14 16:56 Robert F. Garry open
    YeaH do think there will be failures for the vaccines that don't use a stabilized spike. Erica Saphire and others have been preaching this, some folks don't listen. Same with Lassa vaccine, but that's an entirely different story. BTW - Iwas on call yesterday with Erica/NIH so I missed several Zooms.
  7. 2021-01-14 17:02 Kristian G. Andersen open
    Why they did not stabilize that spike I don't know - so simple, people! If we follow this crackpot theory a little bit, knowing that animals that received the OxAZN vaccine were not protected against infection (at all - vaccinated animals had as much virus as unvaccinated animals in the upper airways after challenge). Could the non-stabilized spike lead to a very narrow immune response with very few epitopes exposed, some of which might be suboptimal?If yes, then presumably the virus might be able to escape immunity quite easily by changing a limited set of amino acids - and, presumably, the same/similar set of AAs.We wouldn't see the same happen in natural infections - more complex to escape. We also wouldn't see the same from other vaccines - because, again, more complex.I don't know if this holds up... Seems like a reach to me - albeit, maybe not impossible?

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