So this comment is going to revolve around the supposed loss of T cell epitopes (Figure 3B/3C). I have spent an egregious amount of time giving the benefit of the doubt to these researchers, but alas, I cannot see how they have proven their result.
Just to recap the experiment (with my concerns in parenthesis):
1.) Mice were "immunized" with a pool of either Wuhan or Omicron spike peptides (now does injecting peptides into a mouse's footpad denote sterilizing immunity or just cellular debris to be collected by macrophages).
2.) After 10 days lymph nodes near the area of injection were removed and prepared as single cell suspensions (there are lots of immune cells in lymph nodes - many of which can secrete INFy - many of which are not T cells - there is no indication that any effort was made to separate out CD4+ cells which bind to MHC-Class II which I suppose is the whole reason for using transgenic DRB1*04:01 mice - however, CD8+T cells are the main source of INFy in lymph nodes and they bind MHC Class I - if you want to make a point about DRB1*04:01 they maybe you should only use a lymphocyte that binds Class II MHC - specifically CD4+ cells - there are ways to separate immune cells - magnetic beads or flow cytometry are routinely used to accomplish this).
3.) These cell suspensions were incubated with Wuhan and Omicron spike peptides - activated lymphocytes will secrete INFy which will bind to the biotinylated anti-INFy antibodies bound to the ELISpot plate. Then they add a streptavidin(binds to biotin)-alkaline phosphatase conjugate. And finally a BCIP/NTB which turns a pretty blue/purple in the presence of alkaline phosphatase.
The results certainly do indicate that mice primed with Wuhan are certainly having a reaction to Wuhan peptides. And, mice primed with Omicron are certainly having a reaction to Omicron peptides. That right there is called a secondary immune response. You can't immunize with one set of peptides and then challenge with the same plus another set of peptides - of course the first immunization will have a stronger signal - it's had more time develop. It would be more interesting if they did a Wuhan peptide challenge and after some time an Omicron peptide challenge and after some more time run this assay (but maybe with just CD4+ T cells). If only Wuhan or only Omicron signals were seen then it could suggest imprinting.
Also interesting (which they do not mention) is the T547K peptide clearly has a response for all challenges although it is not listed as a likely candidate for a DRB1*04:01 restricted epitope (Table S9). And making a big deal over the "loss" of the Q493R... DRB1*04:01 restricted epitope when the computer modeling again predicted its loss (umm, maybe the 3 amino acid difference had something to do with that). There's a lot going on in the paper and just accepting their results is a bit ludicrous.
On a lighter note: I enjoy Cara Cara oranges and Honeycrisp apples!
I'm probably one of those that downloaded this study, along with dozens and dozens of others I have also not read.
I only glanced at it, only thinking that this may actually be useful after we get to the worldwide recognition that the recipients of the "gene therapy" have damaged immune systems, politics be damned, and that this "(not a) vaccine" campaign will be viewed in the future as a bigger screw up than war, global warming, slavery, Communism, religious radicalism, centralized world government, or trans ideology.
I am nowhere near done reading/pondering ... but right off the bat I have some hesitation seeing that this paper is coming out of Imperial College London (notoriously bad modeling of the Covid outbreak). Of course, this could be purely coincidental and have absolutely no bearing on this paper. I just noticed it and thought I would make that comment.
Jul 13, 2022·edited Jul 13, 2022Liked by Modern Discontent
RE “No Natural Immunity Cohort” it should once again be mentioned that the study shows an unvaxxed cohort of 18 in supplemental fig S1 (https://www.science.org/action/downloadSupplement?doi=10.1126%2Fscience.abq1841&file=science.abq1841_sm.pdf) but this group disappears after the week 71 reorganization which limits the flow to double-vaxxed. What should be shown here is three lines connecting Wuhan, Alpha, and uninfected double vaxxed Week 55 squares to the new more limited week 71 set. There’s no good reason why the authors didn’t draw the missing arrows here. By my reading, this suggests that the Alpha group were vaxxed before infection, but it could be the other way around. *edit: Actually it seems like recruitment was re-initiated at weeks 71, 83, and 94 so maybe these HCWs aren’t even in the original part of the study. But this still suggests they could simply have “re-recruited” either previous or new unvaxxed subjects.
Your caption for Figure 3 suggests a misread, though I am not sure if this carries through to your whole discussion of this part. 3B is Wuhan-peptide-pool primed mice, 3C is Omicron-pool-primed, both are then tested with both peptide pools, with the results shown per original/variant peptide type. So “The top figure takes transgenic mice primed by either Wuhan or Omicron peptide pools, then introduces individual epitopes from Wuhan spike to measure individual responses to each epitope” would be incorrect. Note that even the authors mess up their description here, at one point saying the Omicron-primed mice were n=7 when it was the Wuhan primed mice who were 7. A gigantic crazy mess, their work.
So this comment is going to revolve around the supposed loss of T cell epitopes (Figure 3B/3C). I have spent an egregious amount of time giving the benefit of the doubt to these researchers, but alas, I cannot see how they have proven their result.
Just to recap the experiment (with my concerns in parenthesis):
1.) Mice were "immunized" with a pool of either Wuhan or Omicron spike peptides (now does injecting peptides into a mouse's footpad denote sterilizing immunity or just cellular debris to be collected by macrophages).
2.) After 10 days lymph nodes near the area of injection were removed and prepared as single cell suspensions (there are lots of immune cells in lymph nodes - many of which can secrete INFy - many of which are not T cells - there is no indication that any effort was made to separate out CD4+ cells which bind to MHC-Class II which I suppose is the whole reason for using transgenic DRB1*04:01 mice - however, CD8+T cells are the main source of INFy in lymph nodes and they bind MHC Class I - if you want to make a point about DRB1*04:01 they maybe you should only use a lymphocyte that binds Class II MHC - specifically CD4+ cells - there are ways to separate immune cells - magnetic beads or flow cytometry are routinely used to accomplish this).
3.) These cell suspensions were incubated with Wuhan and Omicron spike peptides - activated lymphocytes will secrete INFy which will bind to the biotinylated anti-INFy antibodies bound to the ELISpot plate. Then they add a streptavidin(binds to biotin)-alkaline phosphatase conjugate. And finally a BCIP/NTB which turns a pretty blue/purple in the presence of alkaline phosphatase.
The results certainly do indicate that mice primed with Wuhan are certainly having a reaction to Wuhan peptides. And, mice primed with Omicron are certainly having a reaction to Omicron peptides. That right there is called a secondary immune response. You can't immunize with one set of peptides and then challenge with the same plus another set of peptides - of course the first immunization will have a stronger signal - it's had more time develop. It would be more interesting if they did a Wuhan peptide challenge and after some time an Omicron peptide challenge and after some more time run this assay (but maybe with just CD4+ T cells). If only Wuhan or only Omicron signals were seen then it could suggest imprinting.
Also interesting (which they do not mention) is the T547K peptide clearly has a response for all challenges although it is not listed as a likely candidate for a DRB1*04:01 restricted epitope (Table S9). And making a big deal over the "loss" of the Q493R... DRB1*04:01 restricted epitope when the computer modeling again predicted its loss (umm, maybe the 3 amino acid difference had something to do with that). There's a lot going on in the paper and just accepting their results is a bit ludicrous.
On a lighter note: I enjoy Cara Cara oranges and Honeycrisp apples!
I'm probably one of those that downloaded this study, along with dozens and dozens of others I have also not read.
I only glanced at it, only thinking that this may actually be useful after we get to the worldwide recognition that the recipients of the "gene therapy" have damaged immune systems, politics be damned, and that this "(not a) vaccine" campaign will be viewed in the future as a bigger screw up than war, global warming, slavery, Communism, religious radicalism, centralized world government, or trans ideology.
Thanks for the “Organic Chemistry for Dummies” apples vs. oranges (sans controls) example.
I am nowhere near done reading/pondering ... but right off the bat I have some hesitation seeing that this paper is coming out of Imperial College London (notoriously bad modeling of the Covid outbreak). Of course, this could be purely coincidental and have absolutely no bearing on this paper. I just noticed it and thought I would make that comment.
RE “No Natural Immunity Cohort” it should once again be mentioned that the study shows an unvaxxed cohort of 18 in supplemental fig S1 (https://www.science.org/action/downloadSupplement?doi=10.1126%2Fscience.abq1841&file=science.abq1841_sm.pdf) but this group disappears after the week 71 reorganization which limits the flow to double-vaxxed. What should be shown here is three lines connecting Wuhan, Alpha, and uninfected double vaxxed Week 55 squares to the new more limited week 71 set. There’s no good reason why the authors didn’t draw the missing arrows here. By my reading, this suggests that the Alpha group were vaxxed before infection, but it could be the other way around. *edit: Actually it seems like recruitment was re-initiated at weeks 71, 83, and 94 so maybe these HCWs aren’t even in the original part of the study. But this still suggests they could simply have “re-recruited” either previous or new unvaxxed subjects.
Your caption for Figure 3 suggests a misread, though I am not sure if this carries through to your whole discussion of this part. 3B is Wuhan-peptide-pool primed mice, 3C is Omicron-pool-primed, both are then tested with both peptide pools, with the results shown per original/variant peptide type. So “The top figure takes transgenic mice primed by either Wuhan or Omicron peptide pools, then introduces individual epitopes from Wuhan spike to measure individual responses to each epitope” would be incorrect. Note that even the authors mess up their description here, at one point saying the Omicron-primed mice were n=7 when it was the Wuhan primed mice who were 7. A gigantic crazy mess, their work.
I'm finally tackling this one for a post. It turns out there is a giant table in the supplemental materials with the actual raw data, amazing.