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This is such an important paper on the mechanism of side effects for the mRNA vaccines: https://www.sciencedirect.com/science/article/pii/S027869152200206X

Stephanie Seneff, Greg Nigh, Anthony M. Kyriakopoulos, Peter A. McCullough. Innate immune suppression by SARS-CoV-2 mRNA vaccinations: The role of G-quadruplexes, exosomes, and MicroRNAs. Food and Chemical Toxicology, Volume 164, 2022.
https://doi.org/10.1016/j.fct.2022.113008.

fct abstract

I read through and analyzed it for a group of family and friends with whom, at their request, I share covid-19 information. This analysis inspired my first post on Substack.

Part of the ability to mislead on safety and efficacy is because the language is hard to understand. That’s where physicians are supposed to be there for you, providing informed consent. I have maintained from the beginning of the COVID-19 vaccination program, and maintain even more firmly as time goes on, that people were not provided with proper informed consent.

Reading this paper made me incredibly angry. I spend a lot of time not knowing what to do with this information. People trusted. Trust was betrayed. Knowledge can provide worry and heartache. If nothing can be done, what is the purpose of this knowledge? The things that can be done are:
1) for the public: do not continue to participate without proper informed consent;
2) for physicians and scientists: figure out how to treat the damage done.

The paper and the mechanisms it explains are really complicated. The implications of these therapies are complex and hard to understand. There was reassurance that the vaccine-injected mRNA effects would be temporary when, in fact, they may change one’s cellular biochemistry forever, in extraordinarily consequential ways. The vaccines are, in fact, genetic therapy. They affect RNA and DNA expression, translation, and repair. Our genetic and biochemical systems are so complex, I submit they really had no idea what the full impact of these therapies would be. Based on law, regulation, ethics, and historical precedent, they should never have been released without this understanding.

I wrote an informed consent pamphlet in September 2021 that has aged well. My major sources for that pamphlet were the vaccine information sheets themselves. Some highlights (email or send me a message for a copy of the pdf, with references):

• The current vaccines against COVID-19 employ unique mechanisms and were developed on an accelerated timeline.

• The goal of most vaccines is to elicit an immune response (for example, antibody production in response to a viral antigen) that will prevent illness when someone is exposed to a particular infectious agent.

• The Moderna and Pfizer vaccines use a mechanism that has not been used in human vaccines before. They deliver mRNA that causes body cells to produce SARS-CoV-2 spike protein, against which the body produces antibodies.

• The Johnson & Johnson Janssen (J&J) vaccine uses different, but also new, technology. A weakened and modified adenovirus delivers SARS-CoV-2 DNA for the spike protein to human cells. These cells ultimately produce SARS-CoV-2 spike protein, against which the body produces antibodies.

• Typical vaccine development timeline (5-10 years):

1. Preclinical trials, typically in animal models
2. Phase 1 clinical trials in small groups of healthy human volunteers to assess dosing, short-term safety, and immune response
3. Phase 2 clinical trials in larger groups of more diverse human volunteers to further assess safety and immune response
4. Phase 3 clinical trials in tens of thousands of volunteers to assess longer-term safety and vaccine efficacy
5. Regulatory approval by the Food and Drug Administration (FDA)
6. Scaling up vaccine manufacturing
7. Post-licensure vaccine safety monitoring

• This timeline was compressed for current COVID-19 vaccines available in the USA.

• Excluded from these trials:

• Previous confirmed COVID-19 disease

• Pregnant and lactating women (Pfizer, Moderna)

• Children

• Immune compromised

• The trials were only designed to assess whether vaccines elicited expected antibody response with low short-term side effect profile.

• As a potential COVID-19 vaccine recipient, you are a research subject in a Phase 3 clinical trial, with the right to informed consent, that includes risks, benefits, and alternatives, and freedom from coercion or undue influence.

• Potential benefits of COVID-19 vaccines:

• Prevention of COVID-19 disease caused by SARS-CoV-2 coronavirus infection. (COVID-19 disease is a constellation of sign/symptoms (may include fever or chills; cough; shortness of breath; fatigue; muscle or body aches; headache; new loss of taste or smell; sore throat; congestion or runny nose; nausea or vomiting; diarrhea. COVID-19 disease is different than infection with SARS-CoV-2, which can be asymptomatic).

• Early vaccine benefit claims were not that they would prevent infection with SARS-CoV-2, but that they would decrease the severity of disease due to COVID-19.

• The degree and duration of protection is currently unknown.

• Data from current ongoing Phase 3 trials are needed to assess actual long-term benefit.

• Potential risks of COVID-19 vaccines:

• Injection site reactions: pain, tenderness and swelling of the lymph nodes in the same arm of the injection, swelling (hardness), and redness

• General side effects: fatigue, headache, muscle pain, joint pain, chills, nausea and vomiting, and fever

• Severe allergic reactions

• Myocarditis

• Pericarditis

• Blood clots with low levels of platelets

• Guillain Barré syndrome, with muscle weakness and sometimes paralysis

• Antibody-dependent enhancement, resulting in more severe COVID-19 disease when exposed to SARS-CoV-2 than would have occurred without vaccination

• Persistent vulnerability to SARS-CoV-2 infection and COVID-19 disease, with ability to transmit the infection to others

Much of what we were concerned about then is verified in this paper. Though complicated, I’m going to try to tease apart the paper for you, including quotes from it (and, sometimes, my translation—references can be found in the paper itself).

"The utilization of mRNA vaccines in the context of infectious disease has no precedent.

"Vaccination is an endeavor to utilize non-pathogenic material to mimic the immunological response of a natural infection, thereby conferring immunity in the event of pathogen exposure….an implicit assumption behind the deployment of any vaccination campaign is that the vaccine confers the effects of a ‘benign infection,’ activating the immune system against future exposure, while avoiding the health impacts of actual infection.

"In this paper, we explore the scientific literature suggesting that vaccination with an mRNA vaccine initiates a set of biological events that are not only different from that induced by infection but are in several ways demonstrably counterproductive to both short- and long-term immune competence and normal cellular function.

"Since long-term pre-clinical and Phase I safety trials were combined with Phase II trials, then phase II and III trials were combined and since even those were terminated early and placebo arms given the injections, we look to the pharmacosurveillance system and published reports for safety signals. In doing so, we find that that evidence is not encouraging. The biological response to mRNA vaccination as it is currently employed is demonstrably not similar to natural infection. In this paper we will illustrate those differences, and we will describe the immunological and pathological processes we expect are being initiated by mRNA vaccination. We will connect these underlying physiological effects with both realized and yet-to-be-observed morbidities. We anticipate that implementation of booster vaccinations on a wide scale will amplify all of these problems.

"The increasing evidence that the vaccines do little to control disease spread and that their effectiveness wanes over time make it even more imperative to assess the degree to which the vaccines might cause harm.

The authors report a 20201 review, which stated: "Due to the short development time and the novelty of the technologies adopted, these vaccines will be deployed with several unresolved issues that only the passage of time will permit to clarify.” (This is a frightening admission that a great experiment was unleashed on the world).

The authors sorted through mechanisms in the vaccine and their biochemical consequences that lead to theoretical and observed problems with the vaccine:
• The virus should be cleared in the nasopharynx by IgA (a particular type of antibody). "However, since vaccination is given parenterally (via injection), IgG is the principal antibody class that is raised against the SARS-CoV-2 spike glycoprotein, not IgA.”
• The vaccine causes a limited immunologic response: "unlike the immune response induced by natural SARS-CoV-2 infection, where a robust interferon (IFN) response is observed, those vaccinated with BNT162b2 mRNA vaccines developed a robust adaptive immune response which was restricted only to memory cells, i.e., an alternative route of immune response that bypassed the IFN mediated pathways….an effective immune response that prevents the spread of SARS-CoV2 mutants necessarily involves the development of a robust IFN-I response as a part of the innate immune system.”
• The mRNA in the vaccines is packaged in such a way to escape normal immune response, so it can get to the interior of cells and be translated into the spike glycoprotein, which then theoretically elicits the desired immune response. The problem with this packaging and the modification of this mRNA is that spike protein continues to be produced: "A recent early-release study has found that the mRNA in the COVID-19 vaccines is present in germinal centers in secondary lymphoid tissue long after the vaccine is administered, and that it continues to synthesize spike glycoprotein up to at least sixty days post-vaccination.”
• The vaccines likely interfere with interferon signaling. Interferon deficiency correlates with more severe disease. "If, as argued above, the mRNA vaccines interfere with type I IFN signaling, this could lead to increased susceptibility to COVID-19 in the two weeks following the first vaccine, before an antibody response has been initiated.” This has, in fact, been observed.
• Vaccine-induced interference with interferon can result in reactivation of other viruses, e.g. herpes zoster (shingles), Ebstein-Barr (mono), Hepatitis B or C.
• Vaccine-induced thrombotic thrombocytopenia (VITT, characterized by clotting and low platelets) results in "Subsequent clotting cascades cause the formation of diffuse microclots in the brain, lungs, liver, legs and elsewhere, associated with a dramatic drop in platelet count….miR-148a, present in exosomes released by macrophages that are compelled by the vaccine to synthesize SARS-CoV-2 spike glycoprotein, acts to increase the risk of thrombocytopenia in response to immune complexes formed by spike glycoprotein antigen and IgG antibodies produced against the spike glycoprotein.”
• "Multiple case reports in the research literature describe liver damage following mRNA vaccines. A plausible factor leading to these outcomes is the suppression of PPAR-α through downregulation of IRF9, and subsequently decreased sulfatide synthesis in the liver.”

• Exogenous (from the vaccine) and endogenous (from infection) spike glycoprotein can mechanistically cause Guillain-Barre and other neurologic syndromes (tinnitus, hearing loss, vertigo, headache, vision changes, nervous system demyelinating diseases, inflammatory peripheral neuropathies, myositis, myasthenia, limbic encephalitis, and giant cell arteritis). If infection can cause these, shouldn’t the vaccination be helpful? More and persistent spike glycoprotein is produced with vaccination than with infection.

• "A common cause of Bell's palsy is reactivation of herpes simplex virus infection centered around the geniculate ganglion (Eviston et al., 2015). This, in turn, can be caused by disruption of type I IFN signaling.”

• Myocarditis: "S1 segment of the SARS-CoV-2 spike glycoprotein can be cleaved by furin and released into circulation. It binds to ACE2 receptors through its receptor binding domain (RBD), and this inhibits their function. Because ACE2 degrades Ang II, disabling ACE2 leads directly to overexpression of Ang II, further enhancing risk to cardiovascular disease. AngII-induced vasoconstriction is an independent mechanism to induce permanent myocardial injury even when coronary obstruction is not present. Repeated episodes of sudden constriction of a cardiac artery due to Ang II can eventually lead to heart failure or sudden death.”

The above section was an explanation of mechanisms that could result in adverse outcomes. As to whether these are being observed:
• "In mining VAERS (Vaccine Adverse Event Reports System) for ‘signals’ that might indicate adverse reactions (AEs) to mRNA vaccinations, we acknowledge that no report to VAERS establishes a causal link with the vaccination. That said, the possibility of a causal relationship is strengthened through both the causal pathways we have described in this paper, and the strong temporal association between injections and reported AEs. Nearly 60% of all mRNA-injection-related -AEs have happened within 48 h of injection.” The authors acknowledge and discuss critiques to VAERS in the paper.

• "Over the 31-year history of VAERS, up to February 3, 2022, there were a total of 10,321 deaths reported as a ‘symptom' in association with any vaccine, and 8,241 (80%) of those deaths were linked to COVID-19 vaccines. Importantly, only 14% of COVID-19 VAERS-reported deaths as of June 2021 could have vaccination ruled out as a cause (McLachlan et al., 2021). This strongly suggests that these unprecedented vaccines exhibit unusual mechanisms of toxicity that go well beyond what is seen with more traditional vaccines.”

• "we find that there are 27 times as many reports for COVID-19 vaccines as would be expected if its adverse reactions were comparable to those from the flu vaccine.”

The authors go through the data in VAERS that are indicative of:

  1. nerve damage and vagus nerve involvement
  2. heart and liver involvement
  3. thrombosis (blood clotting)
  4. neurodegenerative disease
  5. cancer

Authors’ conclusions (unedited):

"There has been an unwavering message about the safety and efficacy of mRNA vaccinations against SARS-CoV-2 from the public health apparatus in the US and around the globe. The efficacy is increasingly in doubt, as shown in a recent letter to the Lancet Regional Health by Günter Kampf (2021b). Kampf provided data showing that the vaccinated are now as likely as the unvaccinated to spread disease. He concluded: 'It appears to be grossly negligent to ignore the vaccinated population as a possible and relevant source of transmission when deciding about public health control measures.' Moreover, the inadequacy of phase I, II, and III trials to evaluate mid-term and long-term side effects from mRNA genetic vaccines may have been misleading on their suppressive impact on the innate immunity of the vaccinees.

In this paper, we call attention to three very important aspects of the safety profile of these vaccinations. First is the extensively documented subversion of innate immunity, primarily via suppression of IFN-α and its associated signaling cascade. This suppression will have a wide range of consequences, not the least of which include the reactivation of latent viral infections and the reduced ability to effectively combat future infections. Second is the dysregulation of the system for both preventing and detecting genetically driven malignant transformation within cells and the consequent potential for vaccination to promote those transformations. Third, mRNA vaccination potentially disrupts intracellular communication carried out by exosomes, and induces cells taking up spike glycoprotein mRNA to produce high levels of spike-glycoprotein-carrying exosomes, with potentially serious inflammatory consequences. Should any of these potentials be fully realized, the impact on billions of people around the world could be enormous and could contribute to both the short-term and long-term disease burden our health care system faces.

Given the current rapidly expanding awareness of the multiple roles of G4s in regulation of mRNA translation and clearance through stress granules, the increase in pG4s due to enrichment of GC content as a consequence of codon optimization has unknown but likely far-reaching consequences. Specific analytical evaluation of the safety of these constructs in vaccines is urgently needed, including mass spectrometry for identification of cryptic expression and immunoprecipitation studies to evaluate the potential for disturbance of or interference with the essential activities of RNA and DNA binding proteins.

It is essential that further studies be conducted to determine the extent of the potential pathological consequences outlined in this paper. It is not practical for these vaccinations to be considered part of a public health campaign without a detailed analysis of the human impact of the potential collateral damage. VAERS and other monitoring systems should be optimized to detect signals related to the health consequences of mRNA vaccination we have outlined. We believe the upgraded VAERS monitoring system described in the Harvard Pilgrim Health Care, Inc. study, but unfortunately not supported by the CDC, would be a valuable start in this regard (Lazarus et al., 2010).

In the end, billions of lives are potentially at risk, given the large number of individuals injected with the SARS-CoV-2 mRNA vaccines and the broad range of adverse outcomes we have described. We call on the public health institutions to demonstrate, with evidence, why the issues discussed in this paper are not relevant to public health, or to acknowledge that they are and to act accordingly. Furthermore, we encourage all individuals to make their own health care decisions with this information as a contributing factor in those decisions.”

Extra content: Exosomes
You’ve likely seen and heard the word “exosomes” (it was used above). Exosomes are part of the proposed mechanism for the so-called “shedding” that occurs, whereby vaccinated individuals affect unvaccinated individuals. The topic of exosomes deserves its own section. The concept of the vaccinated affecting the unvaccinated was not addressed in this paper.

"An important communication network among cells consists of extracellular vesicles (EVs) that are constantly released by one cell and later taken up by another cell, which could be in a distant organ. Small vesicles known as exosomes, formed inside endosomes, are similar in size to viruses, and are released through exocytosis into the extracellular space to subsequently circulate throughout the body (Yoshikawa et al., 2019). Exosomes can deliver a diverse collection of biologically active molecules, including mRNA, microRNAs (miRNAs), proteins, and lipids (Ratajczak and Ratajczak, 2016). During a viral infection, infected cells secrete large quantities of exosomes that act as a communication network among the cells to orchestrate the response to the infection (Chahar et al., 2015).

"In a collaborative effort by a team of researchers from Arizona and Connecticut, it was found that people who were vaccinated with the mRNA vaccines acquired circulating exosomes containing the SARS-CoV-2 spike glycoprotein by day 14 following vaccination (Bansal et al., 2021). They also found that there were no circulating antibodies to the spike glycoprotein fourteen days after the first vaccine. After the second vaccine, however, the number of circulating spike-glycoprotein-containing exosomes increased by up to a factor of 12. Furthermore, antibodies first appeared on day 14. The exosomes presented spike glycoprotein on their surface, which, the authors argued, facilitated antibody production. When mice were exposed to exosomes derived from vaccinated people, they developed antibodies to the spike glycoprotein. Interestingly, following peak expression, the number of circulating spike-glycoprotein-containing exosomes decreased over time, in step with the decrease in the level of antibodies to the spike glycoprotein.

"Exosomes exist as a part of the mRNA decay mechanism in close association under stress conditions with stress granules (SGs) and P-bodies (PBs) (Decker and Parker, 2012; Kothandan et al., 2020). Under conditions of vaccine-mRNA-induced translation, which could be called “excessive dependence on cap-dependent translation,” there is an obvious resistance to promotion and assembly of the large decapping complex (Kyriakopoulos and McCullough, 2021), and therefore resistance against physiological mRNA decay processes (Decker and Parker, 2012). This would mean that the fate of particular synthetic mRNAs that otherwise would be determined by the common cellular strategy for mRNA turnover involving messenger ribonucleinproteins (mRNPs) is being omitted (Borbolis and Syntichaki, 2015).

"Also, under conditions of overwhelming production of SARS-CoV-2 spike glycoprotein due to SARS-CoV-2 molecular vaccination, it would of course be expected that a significant proportion of over-abundant intracellular spike glycoproteins would also be exported via exosome cargoes (Wei et al., 2021). Mishra and Banerjea (2021) investigated the role of exosomes in the cellular response of SARS-CoV-2 spike-transfected cells. They wrote in the abstract: 'We propose that SARS-CoV-2 gene product, Spike, is able to modify the host exosomal cargo, which gets transported to distant uninfected tissues and organs and can initiate a catastrophic immune cascade within Central Nervous System (CNS)’…. They showed that the microglia readily took up the exosomes and responded to the microRNAs by initiating an acute inflammatory response. The role of microglia in causing neuroinflammation in various viral diseases, such as Human Immunodeficiency Virus (HIV), Japanese Encephalitis Virus (JEV), and Dengue, is well established. They proposed that long-distance cell-cell communication via exosomes could be the mechanism by which neurological symptoms become manifest in severe cases of COVID-19. In further exploration, the authors identified two microRNAs that were present in high concentrations in the exosomes: miR-148a and miR-590. They proposed a specific mechanism by which these two microRNAs would specifically disrupt type I interferon signaling, through suppression of two critical proteins that control the pathway: ubiquitin specific peptidase 33 (USP33) and IRF9. Phosphorylated STAT1 and STAT2 heterodimers require IRF9 in order to bind IFN-stimulated response elements, and therefore IRF9 plays an essential role in the signaling response. The authors showed experimentally that microglia exposed to the exosomes extracted from the HEK293 culture had a 50% decrease in cellular expression of USP33 and a 60% decrease in IRF9. They further found that miR-148a specifically blocks USP33 and miR-590 specifically blocks IRF9. USP33 removes ubiquitin from IRF9, and in so doing it protects it from degradation. Thus, the two microRNAs together conspire to interfere with IRF9, thus blocking receptor response to type I interferons….It appears from [the findings of another study] that miR148a and miR-590 and their inflammatory effects are unique to vaccination-induced SARS-CoV-2 spike glycoprotein production….the available evidence strongly suggests that endogenously produced SARS-CoV-2 spike glycoprotein creates a different microRNA profile than does natural infection with SARS-CoV-2, and those differences entail a potentially wide range of deleterious effects."