Wasn’t there an earlier Japanese study finding similar concentrations of LNPs in those organs? As soon as I saw that the ovaries were collecting that stuff the shot was a big NOPE for my 12-year-old daughter. It still horrifies me that just about all her friends got the shots, no questions asked by their parents. Well, that all healthy kids got it, really, but that’s another rant 😜
"I tend to overlook the materials and methods sections"
Haha, that's where I usually head to first. I don't wait until the results appear suspicious, I assume all study results are suspicious to begin with! And yet ironically, I find the authors' rationale here to be compelling. Accurate sampling for non-injection-site organs was easier than for the injection site, and so the wild variations in injection-site values are just darts that missed the bullseye and should not necessarily condemn the non-injection-site results, which are a lot more consistent for most organs except the hearts (Table 3). In a sense, there was no point attempting to quantify the injection site to begin with. The variations are extreme even at .25 hours (appendix). It's a lot harder to sample "area in the leg that was hit by a needle" than "bladder" since one can "move" and the other can't.
A really great walk-through (I especially got value from the examination of whether distribution can be measured with fidelity by this type of experiment to begin with), and thanks again for the kind link. Not only should this have prompted rescinding the EUA application, it's sickening to think that the results here didn't even wrap until Phase II/III was well underway.
Obviously, your cholesterol-transport mechanism, if correct, would still potentially be competing with capillary fenestration for determination of uptake, and this could account for both glandular and liver-targeting. See figure 5 of https://www.nature.com/articles/nrd4278 (which was cited by Pfizer in their FDA application!).
If the LNP delivers its payload, does it necessarily stay with that cell or is it likely to detach and continue traveling? IOW do we expect a strong relationship between presence of LNP and delivery and presumably expression of the mRNA?
I also seem to recall reading that these LNPs are only metabolized in the liver due to their unusual composition.
I am wondering what your take on this study is now, more than a year later. Now that we have several autopsy reports finding damage to the endothelial lining. Studies that show that the only thing needed to trigger syncytia formation in ACE2 presenting tissue is the spike protein, the fact that capillary beds are made solely of endothelial cells. Overall I would think that the approval of the new bivalent boosters is right up the alley of bad studies like the study #185350.
"These results helped to validate the use of these vaccines in millions of people, and if Pfizer and BioNTech could not bother to follow proper lab procedures or to redo studies how do we trust that these vaccines are safe and effective without any proper studies?"
What does this imply about the review or regulatory process that there wasn't a directive to redo this study? Is this a deviation from normal standards?
Wasn’t there an earlier Japanese study finding similar concentrations of LNPs in those organs? As soon as I saw that the ovaries were collecting that stuff the shot was a big NOPE for my 12-year-old daughter. It still horrifies me that just about all her friends got the shots, no questions asked by their parents. Well, that all healthy kids got it, really, but that’s another rant 😜
"I tend to overlook the materials and methods sections"
Haha, that's where I usually head to first. I don't wait until the results appear suspicious, I assume all study results are suspicious to begin with! And yet ironically, I find the authors' rationale here to be compelling. Accurate sampling for non-injection-site organs was easier than for the injection site, and so the wild variations in injection-site values are just darts that missed the bullseye and should not necessarily condemn the non-injection-site results, which are a lot more consistent for most organs except the hearts (Table 3). In a sense, there was no point attempting to quantify the injection site to begin with. The variations are extreme even at .25 hours (appendix). It's a lot harder to sample "area in the leg that was hit by a needle" than "bladder" since one can "move" and the other can't.
A really great walk-through (I especially got value from the examination of whether distribution can be measured with fidelity by this type of experiment to begin with), and thanks again for the kind link. Not only should this have prompted rescinding the EUA application, it's sickening to think that the results here didn't even wrap until Phase II/III was well underway.
Obviously, your cholesterol-transport mechanism, if correct, would still potentially be competing with capillary fenestration for determination of uptake, and this could account for both glandular and liver-targeting. See figure 5 of https://www.nature.com/articles/nrd4278 (which was cited by Pfizer in their FDA application!).
Thanks, very interesting article!
If the LNP delivers its payload, does it necessarily stay with that cell or is it likely to detach and continue traveling? IOW do we expect a strong relationship between presence of LNP and delivery and presumably expression of the mRNA?
I also seem to recall reading that these LNPs are only metabolized in the liver due to their unusual composition.
Thank you for taking us through the study! 👍🏽💕
I am wondering what your take on this study is now, more than a year later. Now that we have several autopsy reports finding damage to the endothelial lining. Studies that show that the only thing needed to trigger syncytia formation in ACE2 presenting tissue is the spike protein, the fact that capillary beds are made solely of endothelial cells. Overall I would think that the approval of the new bivalent boosters is right up the alley of bad studies like the study #185350.
"These results helped to validate the use of these vaccines in millions of people, and if Pfizer and BioNTech could not bother to follow proper lab procedures or to redo studies how do we trust that these vaccines are safe and effective without any proper studies?"
What does this imply about the review or regulatory process that there wasn't a directive to redo this study? Is this a deviation from normal standards?