1/ 🧵Pfizer’s new mRNA flu trial quietly revealed the problem they can’t quite admit....

It’s not the spike. It’s the platform. It's the LNPs.
What did the data show?
nejm.org/doi/full/10.10… 2/Pfizer’s mRNA flu vaccine = same tech as COVID shots, just a new mRNA coding for the FLU antigen.
So what happened?
Strong fevers, swollen nodes, fatigue, pain which was identical to the COVID pattern.
Same signature, but NO SPIKE PROTEIN.
Does that mean the toxic driver is the lipid nanoparticle (LNP) system itself?

1/ So this is how the vaccine "works" as per this paper. Can you count the lies/misinformation?

https://twitter.com/CanningPharm/status/1993862280736592231

2/ There are really 2 models in this paper but I will focus mostly on the first one.
Model 1:
Visual and written depiction of how mRNA vaccines work by 1. mRNA enters cytosol, 2. ribosomes produce spike antigen, 3. immune memory results.

Model 2: Depiction of how cells protect themselves from foreign DNA, that is the nucleus has a membrane barrier and “a tiny fragment of foreign DNA is harmless because it lacks the tools to insert itself.”

1/10 🧵I am in rant mode today. I feel invisible. I am often dismissed as a "pill counter" despite knowing formulation, stability, & drug kinetics. And it is so important re mRNA-LNP platform. Thread on why it matters, and how AI is making it WORSE. #mRNA Tweet 2/10:
40 yrs as a pharmacist (and only 2 behind a counter). I've crunched LNP biophysics & manufacturing deviations for 4 yrs. But once I reveal my background? Interviews vanish. Academia, biotech, regulators: often treat us as secondary voices. It's structural, not personal. 💔
Full disclosure: I am a hospital and highly trained pharmacist, clinician educator, wrote chapters in textbooks, designed award winning programs, worked at a national level, so admittedly not your average pharmacist.

1/ Here is the standard PBPK model they used. First look at where and how much blood flow. They used IV administration. panel A

https://twitter.com/canningpharm/status/1833164352632823827

2/ so the organ exposed the most is the lung, kidneys, GI tract to liver based on blood flow. But we hardly hear about transfections in kidney or lung. There is a disconnect between uptake into tissues (min) and expression of protein (hrs).

1/The pharmacokinetics of LNPs are exceedingly complex but this paper is the best so far in trying to apply traditional physiologic-based pharmacokinetic modelling with some empirical validation. Let's see if I can explain it to the best of my ability (note paper at end of thread) 2/That figure is a schematic of a liver Kupffer cell, blood or vascular flow, a hepatocyte and interstitial fluid.
through the liver
2. LNPs passively infiltrate the interstitial space and can either be taken up by the Kupffer cells or hepatocyte (transfection)
3. or flow back into lymph nodes and then back again into the vasculature and are recycled
4. once the LNP transfects either the Kupffer or hepatocytes they can undergo one of 4 processes

1/The mRNA in these vaccines is not immunogenic and thus cannot function as a built-in adjuvant. Instead, it seems that the delivery of the LNP stimulates the innate immune system and functions as an adjuvant. Or is it the only adjuvant?

nature.com/articles/s4159… 2/But none of the innate immune sensors, including TLR2, TLR3, TLR4, TLR5, TLR7 and cGAS, seemed to be needed for the immunogenicity of this vaccine.

Only MDA-5, a receptor for long double-stranded RNA, was shown to be important for type I interferon responses and as a built-in adjuvant pathway for antigen-specific CD8+ T cell responses.

There’s dsRNA in those vials as a contaminant.

Well now I have a better idea why autophagy and intermittent fasting works to get rid of the spike protein.
ncbi.nlm.nih.gov/pmc/articles/P… So Moderna looked for ways to make its proteins last longer in the body, including de-ubiquitination. 😲

1/Thanks to @jikkythemouse we have Moderna's Science Day Presentation to investors.
Generally, if you want the truth you read the business filings/presentations as you get better info than on PubMed.
s29.q4cdn.com/435878511/file… 2/ Lets start with:
"mRNA had never been a drug modality, so the pace of learning about mRNA would likely follow a S curve."

Is this an admission, they are on the steep part of the curve and that they're learning more? I thought mRNA was studied FOR YEARS. 🤌

1/My unanswered questions.
1. When the scale up produced only 50% of intact mRNA why not delay for 3 months to get production up over 65%? That’s what happened in reality.
2. Why not start with most at risk, like elderly? 2/It was healthcare workers who were first jabbed.
3. Why are the \/s not serialized? Can’t trace to source or who touched the product. Part of the contract. Standard SOP and usually for the benefit of Pharma so there’s no fraud or counterfeiting.