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I think it's more like, after a vaccination or infection you're now producing 20 different antibodies targeting different sites on the Covid spike. You start o

I think it's more like, after a vaccination or infection you're now producing 20 different antibodies targeting different sites on the Covid spike. You start out producing high levels of the antibodies and less over time, but when you encounter the same virus you ramp up production of all 20 if your levels weren't high enough to prevent infection in the first place. With Omicron maybe only few of those antibodies still work and not as well. That won't be enough to prevent infection. But you can still ramp up production of the ones that work after infection and your body has a good blue print, though the wonders of memory B cells and somatic hypermutation, to start work on more effective Omicron specific antibodies that makes the process easier than developing covid antibodies from scratch.

lamontcg 5y ago
You're missing T-cells. There's something on the order of 1,000 T-cell epitopes against spike, not just 20, and some of them are densely packed in areas of the spike protein that are highly conserved. The spike is cleaved by proteosomes into small segments and those segments are attached to MHC-I in the ER and then shipped off to be expressed on the cell-surface to be identified by T-cell receptors. Those segments are long enough to be recgonized, but small enough that there's a ton of them (and since they're cleaved an no longer attached to the rest of the protein there's no steric hindering or conformation changes or any of that to worry about). And there's still about 80% overlap between Omicron and Delta/Wuhan-hu-1. That number will probably never get down to zero due to the highly conserved areas. CD4+/CD8+ T-cells will therefore still be able to identify infected cells and lyse them or drag them back to have a discussion with some memory B-cells. That is where somatic hypermutation might be important since some of those antibodies will match Omicron's spike and those B-cells can then be amplified and you can get Omicron-specific antibodies being produced -- all without having to start entirely from scratch. But its the CTLs that already identify the Omicron-infected cells which will do the bulk of responding to the virus and clearing the infection. This is also why we don't need to rush to update vaccines to be Omicron-specific or why neutralizing abs really matters that much at all (and if there's Original Antigenic Sin it really may not matter much at all since there may not be much Omicron-specific B-cell or Nabs response to an infection or variant-specific vaccination at all). > SARS-CoV-2 human T cell epitopes: Adaptive immune response against COVID-19 > Over the past year, numerous studies in the peer reviewed and preprint literature have reported on the virological, epidemiological and clinical characteristics of the coronavirus, SARS-CoV-2. To date, 25 studies have investigated and identified SARS-CoV-2-derived T cell epitopes in humans. Here, we review these recent studies, how they were performed, and their findings. We review how epitopes identified throughout the SARS-CoV2 proteome reveal significant correlation between number of epitopes defined and size of the antigen provenance. We also report additional analysis of SARS-CoV-2 human CD4 and CD8 T cell epitope data compiled from these studies, identifying 1,400 different reported SARS-CoV-2 epitopes and revealing discrete immunodominant regions of the virus and epitopes that are more prevalently recognized. This remarkable breadth of epitope repertoire has implications for vaccine design, cross-reactivity, and immune escape by SARS-CoV-2 variants. https://www.sciencedirect.com/science/article/pii/S1931312821002389 https://www.sciencedirect.com/science/article/pii/S193131282...

lamontcg 5y ago

You're missing T-cells. There's something on the order of 1,000 T-cell epitopes against spike, not just 20, and some of them are densely packed in areas of the spike protein that are highly conserved. The spike is cleaved by proteosomes into small segments and those segments are attached to MHC-I in the ER and then shipped off to be expressed on the cell-surface to be identified by T-cell receptors. Those segments are long enough to be recgonized, but small enough that there's a ton of them (and since they're cleaved an no longer attached to the rest of the protein there's no steric hindering or conformation changes or any of that to worry about). And there's still about 80% overlap between Omicron and Delta/Wuhan-hu-1. That number will probably never get down to zero due to the highly conserved areas. CD4+/CD8+ T-cells will therefore still be able to identify infected cells and lyse them or drag them back to have a discussion with some memory B-cells. That is where somatic hypermutation might be important since some of those antibodies will match Omicron's spike and those B-cells can then be amplified and you can get Omicron-specific antibodies being produced -- all without having to start entirely from scratch. But its the CTLs that already identify the Omicron-infected cells which will do the bulk of responding to the virus and clearing the infection. This is also why we don't need to rush to update vaccines to be Omicron-specific or why neutralizing abs really matters that much at all (and if there's Original Antigenic Sin it really may not matter much at all since there may not be much Omicron-specific B-cell or Nabs response to an infection or variant-specific vaccination at all). > SARS-CoV-2 human T cell epitopes: Adaptive immune response against COVID-19 > Over the past year, numerous studies in the peer reviewed and preprint literature have reported on the virological, epidemiological and clinical characteristics of the coronavirus, SARS-CoV-2. To date, 25 studies have investigated and identified SARS-CoV-2-derived T cell epitopes in humans. Here, we review these recent studies, how they were performed, and their findings. We review how epitopes identified throughout the SARS-CoV2 proteome reveal significant correlation between number of epitopes defined and size of the antigen provenance. We also report additional analysis of SARS-CoV-2 human CD4 and CD8 T cell epitope data compiled from these studies, identifying 1,400 different reported SARS-CoV-2 epitopes and revealing discrete immunodominant regions of the virus and epitopes that are more prevalently recognized. This remarkable breadth of epitope repertoire has implications for vaccine design, cross-reactivity, and immune escape by SARS-CoV-2 variants. https://www.sciencedirect.com/science/article/pii/S1931312821002389 https://www.sciencedirect.com/science/article/pii/S193131282...