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Hey TappingTheZen- Correct conclusion? Vaccine ineffective soon?
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01-05-2021, 11:42 AM
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#1
Hey TappingTheZen- Correct conclusion? Vaccine ineffective soon?
Call out because you seem to have some expertise on this subject based on your replies in messomi's thread that was deleted.
This just dropped and where it is posted the conclusion seems to be that it means the vaccine presently being administered will not be effective for long as there are two new strains spreading.
https://www.biorxiv.org/content/10.1...451v1.full.pdf
This just dropped and where it is posted the conclusion seems to be that it means the vaccine presently being administered will not be effective for long as there are two new strains spreading.
https://www.biorxiv.org/content/10.1...451v1.full.pdf
SARS-CoV-2 escape in vitro from a highly neutralizing COVID-19 convalescent plasma
One Sentence Summary: Three mutations allowed SARS-CoV-2 to evade the polyclonal antibody response of a highly neutralizing COVID-19 convalescent plasma.
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In conclusion,we have shown that the authentic SARS-CoV-2 virus, if constantly pressured, has the ability to escape even a potent polyclonal serum targeting multiple neutralizing epitopes. These results are remarkable becausewhile escape mutants can be easily isolated when viruses are incubated with single monoclonal antibodies,usually a combination of two mAbs is sufficient to eliminate the evolution of escape variants and because SARS-CoV-2 shows a very low estimated evolutionary rate of mutation as this virus encodes a proofreading exoribonuclease machinery.
Our data also confirm that the SARS-CoV-2 neutralizing antibodies acquired during infection target almost entirely the NTD and the RBD.
In the RBD, the possibility to escape is limited and the mutation E484K that we found is one of the most frequent mutations to escape monoclonal antibodies and among the most common RBD mutations described in experimental settings as well as in natural isolates posted in the GISAD database . This is likely due to residue E484 being targeted by antibodies derived from IGHV3-53 and closely related IGHV3-66 genes, which are the most common germlines for antibodies directed against the RBD.
On the other hand, the NTD loops can accommodate many different changes, such as insertions, deletions and amino-acid alterations. Surprisingly, only three mutations, which led to complete rearrangement of NTD N3 and N5 loops and substitution to a key residue on the RBD, were sufficient to eliminate the neutralization ability of a potent polyclonal serum.
Fortunately, not all plasma and mAbs tested were equally affected by the three mutations suggesting that natural immunity to infection can target additional epitopes that can still neutralize the PT188-EM variant. Therefore, it will be important to closely monitor which epitopes on the S-protein are targeted by the vaccines against SARS-CoV-2.
One Sentence Summary: Three mutations allowed SARS-CoV-2 to evade the polyclonal antibody response of a highly neutralizing COVID-19 convalescent plasma.
********
In conclusion,we have shown that the authentic SARS-CoV-2 virus, if constantly pressured, has the ability to escape even a potent polyclonal serum targeting multiple neutralizing epitopes. These results are remarkable becausewhile escape mutants can be easily isolated when viruses are incubated with single monoclonal antibodies,usually a combination of two mAbs is sufficient to eliminate the evolution of escape variants and because SARS-CoV-2 shows a very low estimated evolutionary rate of mutation as this virus encodes a proofreading exoribonuclease machinery.
Our data also confirm that the SARS-CoV-2 neutralizing antibodies acquired during infection target almost entirely the NTD and the RBD.
In the RBD, the possibility to escape is limited and the mutation E484K that we found is one of the most frequent mutations to escape monoclonal antibodies and among the most common RBD mutations described in experimental settings as well as in natural isolates posted in the GISAD database . This is likely due to residue E484 being targeted by antibodies derived from IGHV3-53 and closely related IGHV3-66 genes, which are the most common germlines for antibodies directed against the RBD.
On the other hand, the NTD loops can accommodate many different changes, such as insertions, deletions and amino-acid alterations. Surprisingly, only three mutations, which led to complete rearrangement of NTD N3 and N5 loops and substitution to a key residue on the RBD, were sufficient to eliminate the neutralization ability of a potent polyclonal serum.
Fortunately, not all plasma and mAbs tested were equally affected by the three mutations suggesting that natural immunity to infection can target additional epitopes that can still neutralize the PT188-EM variant. Therefore, it will be important to closely monitor which epitopes on the S-protein are targeted by the vaccines against SARS-CoV-2.
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01-05-2021, 11:48 AM
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#2
- ramimotemem
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- ramimotemem
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Originally Posted By katya422⏩
I haven't read much on the vaccine/virus, but isn't this logical?Call out because you seem to have some expertise on this subject based on your replies in messomi's thread that was deleted.
This just dropped and where it is posted the conclusion seems to be that it means thevaccine presently being administered will not be effective for long as there are two new strains spreading.
This just dropped and where it is posted the conclusion seems to be that it means thevaccine presently being administered will not be effective for long as there are two new strains spreading.
If the protein/genetic sequence being injected is that of one strain, wouldn't it logically be rendered useless when the immune system is faced with a strain it doesn't recognize?
Hence the talk about yearly or seasonal vaccines.
01-05-2021, 11:50 AM
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#3
- JustMoved24
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- JustMoved24
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Oh my, war has been waged
New York
01-05-2021, 11:58 AM
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#4
Originally Posted By ramimotemem⏩
It is logical. I'm wondering if this paper actually provides good evidence that the vaccine that is being presently administered may already be becoming obsolete.I haven't read much on the vaccine/virus, but isn't this logical?
If the protein/genetic sequence being injected is that of one strain, wouldn't it logically be rendered useless when the immune system is faced with a strain it doesn't recognize?
Hence the talk about yearly or seasonal vaccines.
If the protein/genetic sequence being injected is that of one strain, wouldn't it logically be rendered useless when the immune system is faced with a strain it doesn't recognize?
Hence the talk about yearly or seasonal vaccines.
I posted a thread yesterday (I think) that seemed to imply there was concern particularly about the SA variant. The media piece went on to downplay it; essentially said they could modify the vaccine easily and it is no big problem.
Except that there will always be some kind of lag time for the development and production of a new version.
I believe the concern is that we may have a situation where we can't get the new version produced and administered quickly enough. Previously there was a good amount of reporting that this virus is much slower to mutate than the flu so this doesn't seem to be something that was expected.
I also saw speculation that this may be part of why some countries are talking about only giving one dose for now, or giving smaller doses.
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