Mar 5, 2022·edited Mar 5, 2022Liked by Modern Discontent
Total biology newb here, but my naive understanding was the lymph drains to the nodes from there into the blood stream. When the original "it stays at the injection site" claims were made, I was puzzled as that's not how I understand the lymph system to work from my studying of exercise physiology. I could be totally wrong, but my understanding was when you exercise you create lots of bits and pieces of detritus (damaged muscle cells, etc) and something like massage is great as it flushes all that "exterior to the damaged cells" gunk up to the lymph nodes and then out to the blood stream to be processed and expelled as necessary. (I remember an admonition to "massage towards the heart" for that reason).
So I recently started reading up on the immune system. In my reading on the immune system I see macrophages et al grab bits and pieces of pathogen (also vaccine), travel to the lymph nodes. Here they can present to T and B cells, get the adaptive response started, etc, etc.
If the lymph nodes drain into the blood, what's to stop the various bits and pieces of uneaten but successfully transported to the lymph node vaccine components (or generated spike) from being piped back into the blood system and thence around the body to wherever they can latch on?
Is it that only the cells with the right receptors (or what have you) can leave the lymph into the blood stream? Or is it more it's impossible to not get eaten by neutrophils, macrophages, etc on the way to the lymph node?
Apologies if this is really dumb. I am trying to learn :D
Your explanation of the % encapsulation part helps me think up a rationale why an "inferior" Acuitas LNP5 was included to begin with - perhaps as a benchmark for the in-house LNP12 formulation. Presumably BioNTech was hopeful but not confident that their own version was ready for prime-time.
Thank you for the kind remarks and links.
Speaking of LNPs, do you know off-hand if there is any research or theoretical argument regarding whether they can be "sequestered" somewhere in tissues or intracellularly without breaking up for a certain time? Emphasis on the "off-hand," I know you've been keeping the LNP question on the back-burner as have I so I'm not asking for any what-you-are-doings to be dropped.
Mar 5, 2022·edited Mar 5, 2022Liked by Modern Discontent
I understand redacting things to hide details of product construction, but it seems to me the things being redacted here are the effects. Is this necessary to prevent reverse engineering?
Because from my naive POV, it seems more they are hiding things that could prove inadequacy of clinical trial testing, rather than "we don't want competitor [X] to work out how we're doing what we're doing and copy our hard work".
Appreciate the follow up. Agreed too, that Mowrey guy is great value.
Indeed it is difficult to parse through their redacted information! Kudos to Brian for providing the un-redacted information. I was looking briefly at another Pfizer document which does indicate that they studied a radioisotope LNP which also showed travel from injection site to mainly the liver (also spleen, adrenal gland, bone marrow, ovaries, as well as trace amounts pretty much everywhere they examined). Interestingly the LNP also contained the mRNA of luciferase (but not much else is mentioned about it - it was not measured). From the paper: Once intracellular, the [3H]-CHE does not recirculate and therefore allows assessment of distribution of the particle. So that would seem to indicate that they do not anticipate movement once an LNP has been taken up by a cell.
I am also quite intrigued by the modifications of the mRNA used in the vaccines. Seems they also added a poly-A tail as well as the pseudouridine swap to help evade immediate degradation by our immune system. So much we don't know ... yet!
Total biology newb here, but my naive understanding was the lymph drains to the nodes from there into the blood stream. When the original "it stays at the injection site" claims were made, I was puzzled as that's not how I understand the lymph system to work from my studying of exercise physiology. I could be totally wrong, but my understanding was when you exercise you create lots of bits and pieces of detritus (damaged muscle cells, etc) and something like massage is great as it flushes all that "exterior to the damaged cells" gunk up to the lymph nodes and then out to the blood stream to be processed and expelled as necessary. (I remember an admonition to "massage towards the heart" for that reason).
So I recently started reading up on the immune system. In my reading on the immune system I see macrophages et al grab bits and pieces of pathogen (also vaccine), travel to the lymph nodes. Here they can present to T and B cells, get the adaptive response started, etc, etc.
If the lymph nodes drain into the blood, what's to stop the various bits and pieces of uneaten but successfully transported to the lymph node vaccine components (or generated spike) from being piped back into the blood system and thence around the body to wherever they can latch on?
Is it that only the cells with the right receptors (or what have you) can leave the lymph into the blood stream? Or is it more it's impossible to not get eaten by neutrophils, macrophages, etc on the way to the lymph node?
Apologies if this is really dumb. I am trying to learn :D
Your explanation of the % encapsulation part helps me think up a rationale why an "inferior" Acuitas LNP5 was included to begin with - perhaps as a benchmark for the in-house LNP12 formulation. Presumably BioNTech was hopeful but not confident that their own version was ready for prime-time.
Thank you for the kind remarks and links.
Speaking of LNPs, do you know off-hand if there is any research or theoretical argument regarding whether they can be "sequestered" somewhere in tissues or intracellularly without breaking up for a certain time? Emphasis on the "off-hand," I know you've been keeping the LNP question on the back-burner as have I so I'm not asking for any what-you-are-doings to be dropped.
I understand redacting things to hide details of product construction, but it seems to me the things being redacted here are the effects. Is this necessary to prevent reverse engineering?
Because from my naive POV, it seems more they are hiding things that could prove inadequacy of clinical trial testing, rather than "we don't want competitor [X] to work out how we're doing what we're doing and copy our hard work".
Appreciate the follow up. Agreed too, that Mowrey guy is great value.
Indeed it is difficult to parse through their redacted information! Kudos to Brian for providing the un-redacted information. I was looking briefly at another Pfizer document which does indicate that they studied a radioisotope LNP which also showed travel from injection site to mainly the liver (also spleen, adrenal gland, bone marrow, ovaries, as well as trace amounts pretty much everywhere they examined). Interestingly the LNP also contained the mRNA of luciferase (but not much else is mentioned about it - it was not measured). From the paper: Once intracellular, the [3H]-CHE does not recirculate and therefore allows assessment of distribution of the particle. So that would seem to indicate that they do not anticipate movement once an LNP has been taken up by a cell.
I am also quite intrigued by the modifications of the mRNA used in the vaccines. Seems they also added a poly-A tail as well as the pseudouridine swap to help evade immediate degradation by our immune system. So much we don't know ... yet!
I certainly appreciate your attempt to sift through these papers - surely it seems they were aware that "it never leaves the injection site" was a blatant lie. Here is the paper I mentioned: https://phmpt.org/wp-content/uploads/2022/03/125742_S1_M4_4223_185350.pdf