Thank you Brian for the deep dive into the Routhu macaque study and for the attributions to my prior delving into the question of IgG4. Indeed, the pie charts in Routhu fig. 1 showing IgG4 dominance after the booster will be on the cover of my first "Vaccines gone Wild" throwback VHS video tape which I hope to have on store shelves soon. Analog media is making a comeback you know : )
Silliness aside, the authors infected these animals in a way that likely bears little resemblance to the natural infection route;
" At week 30, 13 weeks after the final immunization, the macaques were challenged with a total of 6x10^5 PFUs of SARS-CoV-2 BA.5 variant (Omicron BA.5 VOC, titered on Vero-TMPRSS2 cells). The
virus was administered as 2 ml by the intratracheal (IT) route and 1 ml by the intranasal (IN) route (0.5 ml in each nostril). Nasopharyngeal swabs and BAL samples were collected, stored immediately
in an RNA/DNA shield, and processed for viral RNA extraction. After the viral challenge on day 0, nasopharyngeal swabs and BAL fluid were collected in an RNA/DNA shield on days 2, 4, 7,
and 10, and their viral loads were measured."
In referring to their data, the authors suggest at the end of the summary their results show that, "vaccines that lower nasopharyngeal virus may help to reduce transmission" and yet the now peer-reviewed Cleveland Clinic study (which I believe Brian you have been somewhat harsh on in the past) of humans getting infected via natural routes of transmission shows distinctly the opposite effect in that more shots equals more infections.
For me, the IgG4 type switching remains the poster child data proving correct all of us who were worried from the start about unintended consequences and long term unknowns stemming from this novel mRNA transfection technology.
Already one step removed from clinical reality in the "antibody correlates of protection" hall of mirrors the vaccinologists have created based on human data, the macaque studies are that much more disorienting IMO;
Title: Macaque-human differences in SARS-CoV-2 Spike antibody response elicited by vaccination or infection
"Differences between groups included a response to epitopes in the N-terminal domain (NTD) and C-terminal domain (CTD) in vaccinated humans but not vaccinated macaques......"
Thanks for this great analysis of the paper! Even though nothing spectacular appears to result on the scale of months for these macaques, killing them fairly soon after the last of their jabs makes it impossible to know what are the long term health problems resulting from such dominant IgG4.
Yes they're macaques and not quite like us, but they were used and sacrificed because they're similar enough to infer what might be the fate of humans unfortunate enough to be part of this big science fair project run by our government.
Thank you! Right - the whole point of infecting them and then examining the lungs is you expect to see an improvement. But that expectation might not be valid since the virus doesn't cause a lot of damage, so "macaque lungs" are not a very high-resolution immunity measuring instrument.
Great overview on a kinda 'nothing to see here' study, excepting the large IgG4 rises. Maybe healthy macaques aren't all that representative of not-too-healthy humans? Possibly IgG4 only has an effect where there's some pre-existing inflammation.
Would have been interesting if the control group were previously infected at week 0 (ie had natural immunity!)
Right, for humans one of the most interesting age groups is older teens to young adults, this is where the protection of innate immunity gets patchy and you have cases of really extreme Long Covid both without and with injection beforehand. So how does IgG4 move the scale here, is it behind some of the cases of post-injection extreme infection outcomes that have already happened like featured in "Tolerance Maims and Kills?" and does it not matter anyway if natural immunity compensates after the first infection. Can't answer any of that with a small young monkey sample only followed for 10 days.
"A paper by Siddiqui, et al. explored antibody responses after macaques were naturally infected with SARS-CoV-2, and found that anti-spike IgG4 is predictably rare after infection, including several weeks afterward"
This lead me to the following thought, which I thought you were implying (and maybe you explicitly said it):
Infection with SARS-CoV-2 is very different from being injected with the mRNA Gene Therapy treatment.
In the case of natural infection you are definitely getting challenged with far less of the Spike protein and only if those (possibly thousands or millions but not billions) of virus particles make it past your mucous layer and your normal defenses will you see a large surge in the spike protein.
Whereas, with the mRNA gene therapy you are assaulted with billions of the mRNA which get into your cells and goes hog wild. The spike in the Spike protein levels must be enormous within an hour or two of the injection.
Maybe I am wrong.
Also, you seem to be hinting that the experiment was designed to avoid obvious comparisons like:
Are the macaques better off after getting infected if they have been vaccinated vs have not been vaccinated.
My personal guess is that duration of spike expression, B Cells that have already left germinal centers are still encountering spike as they circulate, is the biggest factor. A more conservative theory might be that it's that spike is being retained in germinal centers for so long, and B Cells are being induced to IgG4 switch by T Cells, but it's possible that such long-term retention happens after natural infection as well, without the same result. So until we know more... we don't know why it is happening.
I think the design is wonky because everyone was confused about what the Omicron variants were doing, what the next vaccine target was going to be. So they don't know what they want to examine and show, they just have these previously-injected monkeys and blood draws and they look for something interesting to report. Putting grant money to work.
Thank you Brian for the deep dive into the Routhu macaque study and for the attributions to my prior delving into the question of IgG4. Indeed, the pie charts in Routhu fig. 1 showing IgG4 dominance after the booster will be on the cover of my first "Vaccines gone Wild" throwback VHS video tape which I hope to have on store shelves soon. Analog media is making a comeback you know : )
Silliness aside, the authors infected these animals in a way that likely bears little resemblance to the natural infection route;
" At week 30, 13 weeks after the final immunization, the macaques were challenged with a total of 6x10^5 PFUs of SARS-CoV-2 BA.5 variant (Omicron BA.5 VOC, titered on Vero-TMPRSS2 cells). The
virus was administered as 2 ml by the intratracheal (IT) route and 1 ml by the intranasal (IN) route (0.5 ml in each nostril). Nasopharyngeal swabs and BAL samples were collected, stored immediately
in an RNA/DNA shield, and processed for viral RNA extraction. After the viral challenge on day 0, nasopharyngeal swabs and BAL fluid were collected in an RNA/DNA shield on days 2, 4, 7,
and 10, and their viral loads were measured."
In referring to their data, the authors suggest at the end of the summary their results show that, "vaccines that lower nasopharyngeal virus may help to reduce transmission" and yet the now peer-reviewed Cleveland Clinic study (which I believe Brian you have been somewhat harsh on in the past) of humans getting infected via natural routes of transmission shows distinctly the opposite effect in that more shots equals more infections.
For me, the IgG4 type switching remains the poster child data proving correct all of us who were worried from the start about unintended consequences and long term unknowns stemming from this novel mRNA transfection technology.
Already one step removed from clinical reality in the "antibody correlates of protection" hall of mirrors the vaccinologists have created based on human data, the macaque studies are that much more disorienting IMO;
https://www.biorxiv.org/content/10.1101/2021.12.01.470697v1.full
Title: Macaque-human differences in SARS-CoV-2 Spike antibody response elicited by vaccination or infection
"Differences between groups included a response to epitopes in the N-terminal domain (NTD) and C-terminal domain (CTD) in vaccinated humans but not vaccinated macaques......"
Thanks for this great analysis of the paper! Even though nothing spectacular appears to result on the scale of months for these macaques, killing them fairly soon after the last of their jabs makes it impossible to know what are the long term health problems resulting from such dominant IgG4.
Yes they're macaques and not quite like us, but they were used and sacrificed because they're similar enough to infer what might be the fate of humans unfortunate enough to be part of this big science fair project run by our government.
Thank you! Right - the whole point of infecting them and then examining the lungs is you expect to see an improvement. But that expectation might not be valid since the virus doesn't cause a lot of damage, so "macaque lungs" are not a very high-resolution immunity measuring instrument.
Great overview on a kinda 'nothing to see here' study, excepting the large IgG4 rises. Maybe healthy macaques aren't all that representative of not-too-healthy humans? Possibly IgG4 only has an effect where there's some pre-existing inflammation.
Would have been interesting if the control group were previously infected at week 0 (ie had natural immunity!)
Right, for humans one of the most interesting age groups is older teens to young adults, this is where the protection of innate immunity gets patchy and you have cases of really extreme Long Covid both without and with injection beforehand. So how does IgG4 move the scale here, is it behind some of the cases of post-injection extreme infection outcomes that have already happened like featured in "Tolerance Maims and Kills?" and does it not matter anyway if natural immunity compensates after the first infection. Can't answer any of that with a small young monkey sample only followed for 10 days.
Hmmm, you said:
"A paper by Siddiqui, et al. explored antibody responses after macaques were naturally infected with SARS-CoV-2, and found that anti-spike IgG4 is predictably rare after infection, including several weeks afterward"
This lead me to the following thought, which I thought you were implying (and maybe you explicitly said it):
Infection with SARS-CoV-2 is very different from being injected with the mRNA Gene Therapy treatment.
In the case of natural infection you are definitely getting challenged with far less of the Spike protein and only if those (possibly thousands or millions but not billions) of virus particles make it past your mucous layer and your normal defenses will you see a large surge in the spike protein.
Whereas, with the mRNA gene therapy you are assaulted with billions of the mRNA which get into your cells and goes hog wild. The spike in the Spike protein levels must be enormous within an hour or two of the injection.
Maybe I am wrong.
Also, you seem to be hinting that the experiment was designed to avoid obvious comparisons like:
Are the macaques better off after getting infected if they have been vaccinated vs have not been vaccinated.
My personal guess is that duration of spike expression, B Cells that have already left germinal centers are still encountering spike as they circulate, is the biggest factor. A more conservative theory might be that it's that spike is being retained in germinal centers for so long, and B Cells are being induced to IgG4 switch by T Cells, but it's possible that such long-term retention happens after natural infection as well, without the same result. So until we know more... we don't know why it is happening.
I think the design is wonky because everyone was confused about what the Omicron variants were doing, what the next vaccine target was going to be. So they don't know what they want to examine and show, they just have these previously-injected monkeys and blood draws and they look for something interesting to report. Putting grant money to work.
It's a quote from a vaccinated + Long Covid anecdote