A Washed Up Pharmacist's Musings

Or why most pharmacists don't like drugs. We know too much about them.

Well I’m going to dip my toe into Substack

Hi everyone. Welcome to my musings and reflections on the so called vaccines or better said gene therapy products. My focus is on the regulatory review and on the actual pharmacology of these products. Quality control. Testing. Actual pharmacology.

Much of the information in social media regarding the jabs is superficial, incomplete and sometimes wrong.

Hey. I’m a pharmacist. We like DETAIL. We like to analyze the data and determine risk and apply that risk to our patients. Most people do not see this because it is invisible. Until it is not. Plus, most physicians don’t like detail. They want to big picture because most of the time that is all you need. But for these jabs, the big picture is not good enough. No assumptions can be made since this is a brand new, never before used platform/technology/therapy. It is NOT just a new class of vaccines or a new class of therapy. It is a revolutionary new way of delivering therapy AND a totally unknown pharmacology/therapy. The usual medical heuristics physicians use when they prescribe a new product DOES NOT APPLY. But Public Health, Pharma, Regulators, the Media and the WHO implied it does, which short-circuited most physicians and peoples brains. A very good psy-ops indeed.

Here is my hypothesis on why there is SV40 contamination in the Pfizer vaccines and not in Moderna. This does give benefit of the doubt to the manufacturers but does not exclude more than one reason the SCV40 contamination is there. Its complicated and long but please bear with me.

Something that has not been discussed is that do mRNA vaccines need adjuvants?

The article linked below, discusses the need for an adjuvant because the modRNA IS NOT IMMUNOGENIC. The substitution of N-1-methylpseudoridine makes is “almost silent” to the immune system, so that it can be translated to the spike protein by human ribosomes. “In early attempts to make LNP-mRNA particles, unmodified mRNA synthesized by in vitro transcription was a potent inducer of the production of type I interferons mediated by TLR3, TLR7, TLR8 and RIG-I, which hampered the translation efficiency of the encoded antigen protein and thereby resulted in low immunogenicity.”

Making innate sense of mRNA vaccine adjuvanticity

Not only that, the spike protein made by the mRNA itself is not immunogenic. It may have toxicity, but by itself it cannot make antibodies. The spike protein is a protein and as such is NOT PRO-INFLAMMATORY. In fact, this was nicely shown in an interesting study.

Spike protein is not pro-inflammatory in human primary macrophages: endotoxin contamination and lack of protein glycosylation as possible confounders

So do the LNPs act as the adjuvant in the jabs?

In the review of the EMA files, I find that the reviewers noted an “adjuvant-like” effect of the LNPs on the vaccine. There were increased levels of MCP-1, IL-6, IP-10 at 6 hours post immunization but no further data on time points before or after 6 hrs.

However, more recent data seems to indicate that the LNPs are rather poor at stimulating the adaptive immune system and the dendritic cells. So they (looks like Moderna here) are tweaking the LNPs. This is a de facto admission that the jabs are not providing sufficient antibody response.

Adjuvant lipidoid-substituted lipid nanoparticles augment the immunogenicity of SARS-CoV-2 mRNA vaccines

I propose the reason why researchers are making the LNPs with more of an adjuvant effect, is because they need to remove the dsRNA that is contaminating the vaccines, especially Moderna.

Is dsRNA an adjuvant in addition to or stronger than the LNPs in the 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 as shown in the first article I linked.

Pardi et al discussed dsRNA, as a contaminant in the vaccines and their effects

mRNA vaccines - a new era in vaccinology

“As a mimic of viral genomes and replication intermediates, dsRNA is a potent pathogen-associated molecular pattern (PAMP) that is sensed by pattern recognition receptors in multiple cellular compartments (Fig. 1). Recognition of IVT mRNA contaminated with dsRNA results in robust type I interferon production¹³, which upregulates the expression and activation of protein kinase R (PKR; also known as EIF2AK2) and 2′-5′-oligoadenylate synthetase (OAS), leading to the inhibition of translation³⁸ and the degradation of cellular mRNA and ribosomal RNA³⁹”

So you need to get rid of the dsRNA, which is a natural contaminant of the in vitro transcription process, otherwise it will overwhelm the cells and no spike protein will be produced. However, that is how natural viral infections cause an immunological response.

Pfizer developed a method to remove 90% of the dsRNA

A Facile Method for the Removal of dsRNA Contaminant from In Vitro-Transcribed mRNA

And here is what they used as filters for their 2 step ultrafiltration/diafiltration of the the bulk mRNA solution. It was stabilized cellulose. But I am not sure it is the exact method used in the article quoted above as that method requires ethanol. But it could be an updated version.

Moderna (I think!!) used a fast protein HPLC method but because I don’t have access to the data, like I do for Pfizer I cannot be certain. This likely results in higher levels of dsRNA than the cellulose method. I cannot confirm but Milano et al below also suggests this to be true.

Is dsRNA the cause of myocarditis due to the jabs?

Because dsRNA is a potent PAMP that is sensed in many cells, then even small amounts WHICH ARE TRANSFECTED along with the mRNA as a contaminant can potentially cause adverse effects. In fact, dsRNA contamination is a potential cause of myocarditis.

An article which came out in late 2021 by Milano et al, proposed that the dsRNA contamination in the jabs played a role in the occurrence of myocarditis.

Myocarditis and COVID-19 mRNA vaccines: a mechanistic hypothesis involving dsRNA

It is worthwhile to read the whole thing. Here is an excerpt:

Regarding the consequences of the presence of dsRNA (Figure 1), on the one hand, dsRNA could provide an advantage (intrinsic adjuvant) by inducing a high immunological response, which is obtained with COVID-19 mRNA vaccines. However, this remains an hypothesis and there are no dedicated studies evaluating a possible benefit of dsRNA in mRNA vaccines conferring an added protection against SARS-CoV-2. On the other hand, dsRNA could boost the induction of some uncontrolled and potentially detrimental immune-inflammatory reactions, such as myocarditis (Figure 1). This leads to the next unavoidable question: can the presence of dsRNA in mRNA vaccines, even at low concentration, explain some of the undesired effects? In the case of myocarditis, it should be noted that when packaged in lipid nanoparticles, dsRNA is preferentially transferred to phagocytic monocytic-derived cells, such as macrophages and dendritic cells, which are key actors in immunity [24]. Recent studies indicate that precursors of dendritic cells patrol the blood and communicate with immature dendritic cells residing in peripheral tissues such as the kidneys, skin and myocardium. Dendritic cells trigger immune responses in lymphoid tissues upon early sensing of infectious pathogens. Globally, dendritic cells form a sentinel network that modulates immune responses with the distinct ability to produce protective immunity or tolerance to self.

Now in January 2023, the EMA held a virtual workshop on the myocarditis post COVID-19 vaccination. There was an interesting presentation by Pardi et al regarding the innate mechanisms of mRNA vaccines (the same Pardi quoted earlier). This too is worth reading in full.

Innate mechanisms of mRNA vaccines

Here they ADMIT that the dsRNA contamination (‘keeping it a little bit dirty”) is THE DIRTY SECRET for the adjuvant/side effects of the mRNA vaccines. Moderna’s solution is to invent a new T7 polymerase which does not result in ANY dsRNA. They think this will prevent the reactogenicity. And based on the first article posted, they are working on making the LNPs act more as an adjuvant to make up for the removal of dsRNA.

An engineered T7 RNA polymerase that produces mRNA free of immunostimulatory byproducts

Is dsDNA a potential adjuvant in the mRNA vaccines?

As many now know, Kevin McKernan, a genomics expert has documented large amounts of dsDNA contamination in the Pfizer vaccine, and less in the Moderna vaccine. Furthermore, he found an SV40 promoter in the vaccine WHICH HAD NOT BE DISCLOSED TO THE REGULATORS. Ok to me that is a real problem, but a topic for another substack.

Executive Summary of the FDA VRBPAC presentation on dsDNA contamination in mRNA vaccines

So other than its potential oncogenic nature and infectious nature, guess what? dsDNA is a very good adjuvant

Induction of innate and adaptive immunity by delivery of poly dA:dT to dendritic cells

“In addition, cytosolic accumulation of double-stranded DNA (dsDNA) is a potent adjuvant that induces the activation of innate immune signaling pathways^5–7.”

Now I don’t know if the SV40 promoter is a potent adjuvant like substance and any comments to that effect would be appreciated.

Hypothesis for dsDNA contamination

Pfizer developed their vaccine with the ability to remove most of the dsRNA, and it appears Moderna less so. They both knew there were risks and I believe both manufacturers knew by mid 2021 that the level of dsRNA was a risk factor for myocarditis.

So Moderna invents a new T7 promoter which gets rid of all dsRNA and works on the LNPs to make them be more reactogenic. So to test this theory, the most recent manufacturing of Moderna vaccine should have more dsDNA to make up for the decrease in dsRNA until their new LNPs get developed. We need to see if that is true, but preliminary data shows this is the case. More to come later.

For Pfizer, they used the SV40 promoter and contamination of all their commercial batches. I think they KNEW they would not get enough immunogenicity unless they deliberately added some dsDNA or dsRNA. They went with the dsDNA and therefore caused less myocarditis. I have more data for another substack which looks at the developement of the Pfizer vaccine and the levels of dsDNA between Process 1 and Process 2 and where each of the Process 1 batches were used in the clinical and non-clinical testing of the jabs. Stay tuned.

Because, a lot of this is new to me, an older washed up pharmacist, and no vaccinologist or genomic courses, any comments or corrections would be much appreciated.

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