Yale’s 2023 myocarditis study explains that the LNPs are “highly inflammatory,” naming lipids in synergy with RNA as myocarditis “likely inflammatory driver.”

Yale & Genentech studies show RNA vaccine inflammation irrespective of Nobel Prize "non-inflammatory" RNA Modifications.

2022 “The immunostimulatory activity of the modRNA is highly dependent on the lipid formulation.” [115] “Immunostimulation is defined as the unwanted overactivation of the immune system…” [129]

---

Updated Synopsis- Detailing the vaccine inflammatory path irrespective of vaccine component modifications.

May 2023 with November 2023 additions: Heather Hudson

Introduction: The below work was written in early 2023, with additions made from October to November 2023. This Executive Brief and the accompanying Executive Summary are sent to lawmakers and investigators. This work includes concerns with the LNPs published in LNP co-developer co-authored studies from August 2020, just months before the EUA approval of the COVID-19 mRNA LNP vaccines. Studies and documentation on the pre-pandemic reactions to the lipids in drugs that Pfizer’s 2022 internal document lists as “similar lipids” to the Pfizer COVID-19 mRNA LNPs are of importance. As in their COVID-19 mRNA vaccine applications worldwide, the key lipid LNP ingredients ALC-0315 and ALC-0159 are listed as “novel,” but the lipid components PEG2000 – and the “similar” lipids have a detailed history of adverse events. Studies show these lipid adverse events did not simply stop taking place in COVID-19 vaccines.    

COVID-19 vaccine consumers are told by vaccine developers, health agencies, media, and Nobel Prize Committee that pseudouridine modifications produce a safer vaccine. [115][118][122] In fact, in December 2020, Drew Weissman stated, “Katie Kariko and I started working on RNA to try and understand why it was so inflammatory… we figured out how to make it non-inflammatory.” [121] But this 2022 Modified RNA vaccine cytokine study states, “However, RNA vaccines against COVID-19 [Pfizer/Moderna] which use modRNA with a greatly reduced innate immunostimulatory activity, still elicits systemic adverse events…” It also describes the immune signaling “effect that was unexpectedly amplified by certain lipids used in vaccine formulation incorporating N1-methyl-pseudouridine-modified RNA …” [115][116][117] 

Then, Yale’s 2023 myocarditis study explains that the LNPs are “highly inflammatory,” naming lipids in synergy with RNA as a myocarditis “likely inflammatory driver.” [110] Pfizer’s 2022 COVID-19 vaccine internal document also states that lipids may activate “immune responses” and “pro-inflammatory processes.” [2] Explaining how animals were less sensitive to inflammatory responses than humans, the above 2022 cytokine study states, “We investigated the ability of lipid-formulated RNA vaccines to trigger innate immunity. We uncovered the key role of IL-1 in triggering the release of other pro-inflammatory cytokines associated with cytokine release syndrome (CRS), with humans being markedly more sensitive than mice.” The study found “inflammatory responses in humans that were not predicted from preclinical studies.” [115] Pfizer’s 2022 internal document also states, “Currently, there are no good, established animal models to study vaccine-associated myocarditis and pericarditis.” [2]

As such, questions surrounding the lipids and vaccines deserve answers. The following Brief and Executive Summary provide key studies in these COVID-19 vaccine safety questions as follows:

1. In 2020, the Lipid Nanoparticle was a little-known/unknown science according to the Pfizer Covid-19 mRNA vaccine LNP co-developer: Before the Covid-19 mRNA vaccines were approved under the Emergency Use Authorization (EUA), LNP studies and development were little-known areas of science that struggled to find its footing, funding, and success largely due to safety issues (seen in articles herein). Pre-pandemic nano lipids were mainly used as carrier lipids in cancer drugs. Some required pre-medication to avoid lipid adverse reactions (including the “similar” lipids to the COVID-19 lipids). However, LNPs were little known by the public per Covid-19 mRNA vaccine LNP co-developer Peter Cullis, who states in 2022, “Then in November [2020] …lipid nanoparticles became really popular. Nobody had ever heard of a lipid nanoparticle before, but in the last year and a half, they certainly have.”[11][12][23]

2. What is an LNP? The lipid nanoparticle (LNP) can be thought of as a bubble that surrounds the drug or therapy (payload) that is to be delivered in the cells (for example, mRNA gene therapy). The LNP bubble shape forms as numerous cone-shaped individual lipid molecules attract to one another to form a bubble shape with a hollow center; the bubble then houses the payload, which can include more LNPs along with gene therapy such as mRNA, siRNA, etc.  

3. What do LNPs do? The LNPs provide a means for the therapy or drug to be carried inside the LNP bubble to travel in our body and enter our cells that are naturally surrounded by their own lipid layer. The cells allow the LNP in via an exchange of charges of the components when the LNP lipid and the natural cell lipid join. Inside the cell, the LNP falls apart and releases its payload. Studies show the LNPs sometimes do not enter the cell (as was intended), or they are not adsorbed (due to adsorption rates), and they can circulate in the body instead of entering the cell. Also, per the studies, sometimes LNPs can fall apart before being taken up by the cells, and the lipids and their payloads circulate in the body. For the LNPs that enter cells, this study describes “…re-distribution of the respective lipids from the tissues into which they have distributed as the LNP back to plasma where they are eliminated.”[44][75]

4. LNP lipids remain in the human body “four to five months” 2021 EMA Comirnaty [67]

5. What is PEG? PEG (Polyethylene Glycol) is an emulsifier that helps prolong the life of the LNPs and stabilize the LNP bubble structure. PEG-coated lipids are called PEGylated lipids. PEG is used in COVID-19 mRNA vaccines and pre-pandemic lipid and liposomal drugs shown herein. Some people have a true allergy to PEG, and some can have a pseudo allergy with infused or injected PEG. Both reactions can be mild or serious. PEG has a crossover reaction with structurally similar Polysorbate 80 (used in Novavax and AstraZeneca vaccines). Novavax also contains synthetic lipid nanoparticles, as seen on the Novavax fact sheet. [130]

6. PEG and LNP safety issues: In July 2020, LNP co-developer Peter Cullis co-authored this study, showing PEG is immunogenic and LNP biophysical properties (shape, size, etc.) can also elicit unwanted immune response as the body can mistake nano molecules for virus molecules. “PEG can generate unwanted adverse effects such as complement activation, which may result in hypersensitivity reactions…and anaphylaxis…” [72] CARPA is a frequent side effect of intravenous therapies with nanoparticle-containing drugs and biologicals that are recognized by the immune system as foreign. [94]

7. Details on the modifications that were said to make the vaccine technology safe and studies showing systemic inflammation and innate immune signaling irrespective of these modifications: This 2021 study called The Critical Contribution of Pseudouridine to mRNA COVID-19 Vaccines, describes innate immunogenicity in mRNA development as a challenge and then states, “the “answer” to this challenge came from well-known RNA modification, pseudouridine (Ψ).” This study further explains Toll-like receptors (TLRs) 7 and 8 (or TLR7/8) inflammatory mechanisms are suppressed by the pseudouridine modification. [119]

However, the 2022 Genentech study states, “We investigated the ability of lipid-formulated RNA vaccines to trigger innate immunity… Surprisingly, the reactogenicity of RNA vaccines was not necessarily due to the TLR7/8 agonism, as IL-1 release was observed using vaccines containing N1-methyl-pseudouridine-modified RNA. Instead, the lipid components used to formulate these vaccines substituted for unmodified RNA in eliciting the IL-1 response.”

The study then shows IL-1 [cytokine] triggers the release of other pro-inflammatory cytokines associated with cytokine release syndrome [CRS or cytokine storm], stating, “Unlike humans, mice preferentially upregulated anti-inflammatory IL-1ra relative to IL-1, [inflammatory cytokine] protecting them from uncontrolled systemic inflammation.” And later stating, “However, RNA vaccines against COVID-19… still elicits systemic adverse events…” [115]

8. Yale 2023 study details on the “highly inflammatory” LNPs and immune responses: In 2023, twenty-six Yale physicians developed the above COVID-19 vaccine myocarditis cytokine study, which states, “the LNP component of the vaccine alone was found to be highly inflammatory,” informing, “the LNP delivery platform in synergy with vaccine-vectored antigens is more likely the driver of an exaggerated immune cytokine response driving cardiac pathology after vaccination in susceptible individuals.” [110][See pg. 75 Executive Summary]

• 2020, Covid-19 mRNA vaccine PEG lipid anaphylaxis/anaphylactoid reactions prompt a safety signal just after the December COVID-19 Pfizer mRNA vaccine approval. [6]

• 2021, FDA fact sheet: Myocarditis warnings are placed on COVID-19 mRNA vaccine. 

• 2022, Pfizer internal paper: “The immune responses to mRNA may not be sufficiently turned down and drive the activation of an innate and adaptive immune response.”[2]

• 2022, we learn of “RNA vaccine-associated innate signaling” [115]

• 2022/2023, lipid / RNA C-19 mRNA vaccine myocarditis roles described. [2][110][115]

• 2022/2023, COVID-19 vaccine immune reactions, autoimmune reactions, and adverse events are acknowledged by Mayo Clinic, among other studies (see) [2][53-57][91].

9. Current lipid reactions resemble pre-pandemic lipid reactions, which can be mild, severe, or fatal; elicit complement-activated immune dysregulation, autoimmune disorders, and adverse events beyond allergy: This 2022 study “focused on HSRs to Comirnaty, as it consists of PEGylated LNPs that resemble PEGylated liposomes, and “lessons” learned from nanomedicine research suggest that nanoparticles (NPs) injected into the blood can cause so-called “infusion reactions” whose symptoms are very similar, or the same as those reported HSRs to LNP-mRNA vaccines...” [28]

10. Can we learn about reactions and rates from the “similar” lipid delivery drug? Onpattro lipids are described as “similar lipids” to Covid-19 mRNA vaccine lipids by Pfizer in their internal documents. [2] Per the FDA fact sheet and Onpattro studies, treatment requires monitoring, premedication with a corticosteroid, acetaminophen, and antihistamines (H1 and H2 blockers) prior to ONPATTRO infusion due to the toxicity of the lipids. Reactions occur at a “common” rate. [3] Could patient monitoring factor in accurate reaction rate reporting?    

11. COVID-19 vaccine AEs are reported as “rare,” but are they?  Reference [57] includes thirty-one autoimmune cases after COVID-19 vaccine; twenty-nine cases are attributed to Pfizer; twenty-seven are new-onset, and one death was recorded, per the single medical center study. Case onset greater than twenty-eight days after vaccine dose two was excluded.

12. Little known long lipid circulation times and risk of complement activation, autoimmune conditions, and loss to reporting: COVID-19 vaccine adverse event studies typically include AEs that take place within a thirty-day to six-week timeframe. The Pfizer FDA EUA states, “Adverse events considered plausibly linked to vaccination generally start within 6 weeks of vaccine receipt. Therefore, a 2-month follow-up period may allow for identification of potential immune-mediated adverse events that began within 6 weeks of vaccination.” [66] As such, “delayed reactions” are frequently excluded from studies, although Pfizer states, “the immune responses to these lipids has not yet been fully understood.”[2]

• “Nano-sized drugs have long circulation times associated with higher toxicity.” [27]

• PEG can generate unwanted adverse effects such as complement activation. [6][86][72]

• Cleveland Clinic: “If your complement proteins are working too hard and activating too frequently, you may be at risk for several autoimmune or inflammatory conditions.”[30]

• American Cancer Society: “Delayed reactions can happen up to a few days or weeks after receiving your infusion. Infusion reactions can be mild, moderate, or severe.” [101]

• mRNA and spike found in plasma and lymph nodes several weeks post vaccination. [120]

COVID-19 vaccine lipids, RNA, and Spike, have long circulation times and are linked to adverse events. Yet, regulatory agencies have not conducted studies determining whether traditional six-week vaccine AE-associated timeframes correlate to COVID-19 mRNA vaccines. Without this data, all COVID-19 vaccine AE data on frequency or rate of adverse events is incomplete.

13. Unpredictable nano and lipid reactions -lack of uniform terminology complicates matters: In the 2018 article, “Roadmap and strategy for overcoming infusion reactions to nanomedicines,” Szebeni et al. state, “Despite decades of research…, it is largely unknown why some patients develop these reactions while others do not. The lack of uniform terminology and classification of the reactions further complicates the issue. As such, acute IRs cause substantial stress among patients and their families as well as care providers and regulatory agencies…” [9]

14. In studies, Lipid, PEG, LNP, and nanoparticle infused or injected reactions are called:

• HSRs, HSR-like reactions, and Hypersensitivity Reactions (IgE OR non-IgE mediated).

• Anaphylaxis and Anaphylactoid reactions. (See study explanation in item 15 below.)  

• CARPA (Complement Activated Reaction Pseudo Allergy).

• True Allergy OR Pseudo Allergy, Non-Allergy Reactions, or Allergy-Like Reactions.

• IRs and IRRS- Infusion reactions (even though the formulations may be injected).

15. High rates of lipid reactions unrecognized in medicine: This 2018 article, co-authored by Janos Szebeni (who learned to make liposomes with Katalin Kariko), states, “These reactions are known to be pseudoallergic or anaphylactoid.” It continues, “pseudoallergy may represent as high as 77% of all immune-mediated immediate HSRs …implying hundreds of thousands of reactions and numerous fatalities every year... Many of these reactions involve the activation of the complement system, an essential humoral arm of innate immunity. Complement activation-related pseudoallergy (CARPA) is linked to adverse events evoked by several liposomal and micellar formulations, nanoparticles, radiocontrast agents, and therapeutic antibodies...”[81]

16. PEG or PEGylated lipid reactions are relatively unknown outside the nanomedicine field: This 2020 Science Magazine article (written just after Covid-19 mRNA vaccine approval) shows at least eight people developed severe allergy-like reactions, Szebeni warned that the mechanism behind “PEG-conjugated anaphylaxis is relatively unknown,” stating, “PEG triggers two other classes of antibodies involved in innate immunity called the complement system.” [6]

---

17. Pfizer LNP co-developer -LNP safety and efficacy- Biomolecular Corona: The following 2020 study on the LNP biophysical features was published just months before the Pfizer Covid-19 vaccine approval. Peter Cullis (co-developer of Pfizer LNPs) co-wrote this work. It states, “Even the same LNP tested in different animals, in different patients, or in the same individual over time might acquire different coronas, with potentially important implications for LNP clearance, target tissue accumulation, and efficacy.” “In addition to the interference with cellular interactions, PEG can generate unwanted adverse effects such as complement activation, which may result in hypersensitivity reactions… even anaphylaxis.” “PEGylation can trigger production of antibodies that preclude the possibility of repetitive administrations… PEG alternatives such as polysarcosines might be a possible solution to this problem…” [72]

18. Pfizer LNP co-developer “Nanomedicine approach should be replaced”: Seen in the above 2020 study, “The physicochemical characteristics of LNPs change upon corona formation, which is specific to the biological environment in which particles are administered. As a consequence of this specificity, the same LNP will possess a different corona for each individual and each disease… This emphasizes, once more, that the “one size fits all” nanomedicine approach should be replaced with a more personalized framework...” [72]

• This 2020 study that warns of the LNP issues was published just months before the Pfizer Covid-19 mRNA vaccine FDA EUA approval, but it was not shared with the consumer.

• Despite the above, upon the vaccine roll-out (and repeatedly after), the consumer was assured that pseudouridine modifications made the vaccine safe and effective. [121][122]

19. Similar 2020 LNP corona study: Another 2020 study on LNP Corona efficacy and safety states, “In other words, identical NPs may form different protein corona profiles in patients with various diseases, significantly affecting the safety and therapeutic efficacy of the NPs across patients; however, those very differences in the protein corona that constitute a huge shortcoming for therapeutic applications can be exploited for disease detection ex vivo.” [79]

20. PEG antibodies reduced efficacy and biodistribution: This 2022 study states, “The first injection of PEGylated drugs induces anti-PEG antibodies, which then bind and form an immune complex with the second dose of the PEGylated compound to activate the complement system. This results in the opsonization of PEG with C3 fragments and enhanced uptake by Kupffer cells in the liver and can result in altered drug pharmacokinetics/biodistribution and reduced efficacy in subsequent doses.”[86] Similar reduced efficacy studies are found in the Executive Summary.

---

21. Despite their studies and data, 2020 Pfizer scientists state the risk is negligible: In December 2020, PEG LNP anaphylaxis-like events were seen within days of the Pfizer mRNA-LNP vaccine EUA approval; when asked about the AEs, the BioNTech VP stated, “…that given the low amount of lipid and the intramuscular administration, the risk was negligible.” [6].

a) Re: “low amount,” a “safe dose” of LNPs in humans is not established by a regulatory agency: “The study designs only included a single experimental group each with a variant of BNT162b2 (V8 or V9 variant), with no dose-response assessment or specific experimental groups for the LNP alone or its novel excipients.” “…there is no toxicological data on the LNP alone or its specific novel excipients.” 2021 EMA Assessment report Page 49. [67]

b) Re: “low amount,” unpredictability and timing of the LNP adverse event shows dose dependence is an independent factor of AEs: The American Cancer Society and others have shown that IR reactions take place “immediately, upon first contact, or with a delayed reaction.” Many reactions have taken place within the first few minutes of infusion, and others have taken place weeks after infusion. As such, these reactions occur as very little LNP enters (or remains) in the body. The Onpattro “similar” lipid drug clinical trials also show that 20.8 % of patients had a reaction to the lower dose drug compared to 7.7% who had a reaction to the higher dose of the drug. [100]

c)  Re: “low amount,” LNP corona studies show biophysical features are associated with unwanted outcomes: Also seen in this 2021 LNP study, which states, “Depending on their characteristics, LNPs can cause various in vivo immune effects: activation of immune cells, inflammation, adaptive immune response, and in some cases, complement activation and complement activation-related pseudoallergy (CARPA)…” [63] 

d)  Re: intramuscular administration: 2015 study mRNA-LNP intramuscular injection depth can alter biodistribution and determine whether injections disseminate to the liver or stay in the arm/muscle: In 2015, Katalin Kariko- BioNTech VP, Drew Weissman- mRNA developer, and four Acuitas Therapeutics (LNP developer) scientists showed biodistribution of the mRNA-LNP formulation could be altered via route of delivery. They also showed the depth of muscle injection could determine whether the formulation was distributed mainly to the liver or remained in the muscle tissue. The study states, of the administration of mRNA-LNP complexes, “Depending on the site of injection, both local protein production and dissemination to the liver occurs. ...with intramuscular injection, the depth into the muscle also determined whether the majority of protein produced was in the muscle, for superficial injections, or in the liver, for deep muscular administration (unpublished observations).” [58]

Please credit this image to this Executive Summary document if re-posting.

22. Similar Lipids 2015 and 2022: Scientists in the 2015 study above compare the lipids used in the mRNA-LNP formulation to the lipids in the drug (Onpattro), which requires pre-treatment and assessment to circumvent known LNP complement-activated adverse hypersensitivity-like events. The adverse events table for this drug includes connective tissue disorders (AKA autoimmune adverse events), along with other reactions listed as common reactions. [58][99] In 2022, Pfizer wrote, “Onpattro lipids are similar and a relevant lipid to Pfizer Covid-19 mRNA vaccine lipids.” In this same 2022 Pfizer internal document, the scientists express “well-known” vaccine-associated autoimmunity. [2] Then, in 2023, Alqatari et al. pointed out that “Deep molecular characterization techniques have been used to investigate the severity of COVID-19 [infection].”  “However, no studies have been conducted on Covid-19 vaccine-related autoimmune response.” [57]

23. 2020 FDA EUA application for COVID-19 vaccines, Similar drug, Similar Platform, and Similar Construct data: Per the FDA, “supportive data Available for the construct are among the requirements to support first in human FIH clinical trials... Toxicology data and clinical data accrued with other products using the same platform may be possible to use to support FIH clinical trials.” Nonclinical studies of a COVID-19 vaccine candidate exist in part to define safety characteristics, immunogenicity and identify potential vaccine-related safety risks. [78] The FDA defines recommendations for inclusion of safety data in “similar drugs.” Onpattro is an “other product” with a “similar lipid platform.” Why wasn’t Onpattro safety data provided?   

24. 45% of the 2021 pre-clinical trials for LNP-based drugs include safety warnings:  Considering “dispensing with certain lipid safety studies” was suggested in a 2022 FDA Public Workshop [95], it should be known that the safety profiles of Twenty upcoming LNP-based drugs with pre-clinical studies underway show 45% of these drugs include safety warnings. Of the nine safety warnings, eight are for liver toxicity. Some of the drugs are not yet in the phase to determine safety warnings. [63] See section FF in the Executive Summary. 

25. PEG Reactions are little known to physicians pre-pandemic: A 2018 University of North Carolina study called “Physician Awareness of Immune Responses to Polyethylene Glycol‐Drug Conjugates” found of the physicians polled, “Only 22% of physicians who prescribe PEGylated therapeutics are aware of APA [Anti Peg Antibodies]. Only 35% of physicians who prescribe PEGylated drugs know that PEG is a part of that drug compound.” “Physicians who prescribe PEGylated therapeutics should undergo targeted education.” It says, “Given the low levels of awareness, it may be important to quantitate the efficacy of knowledge transfer from the research community to clinicians, especially on topics of patient safety.” [93] Pre-pandemic PEGylated lipid and current mRNA technology PEGylated lipid (LNP) adverse events are documented in studies. Widespread recognition of these adverse events is crucial to treatment.

27. The role of LNP inflammation and immune signaling in synergy with antigens and potential contaminants: “Our studies revealed that not only the direct TLR7/8-mediated sensing of the nucleic acid component, but also the physiochemical and possibly lytic properties of the vaccine lipid particles themselves, determine the cytokine induction profile of lipid-formulated RNA vaccines. Our data indicate that the immunostimulatory activity of the modRNA is highly dependent on the lipid formulation…” [115]

28. The COVID-19 mRNA vaccine antigens, contaminants, associated cytokines, and inflammasome activation: The studies herein have shown that LNPs can amplify immune signaling and potentially act in synergy with antigens [110][115]; here, COVID-19 vaccine antigens and modRNA potential sources of immune signaling, are discussed.

• Spike- The role of Spike antigen in COVID-19 vaccine myocarditis, endothelial cell damage, and blood clotting are discussed in studies. [2] Of note, in SARS‐CoV‐2 infected patients, “inflammasome activation derives in part from the spike protein.” [128]

• Impurities and Contamination- Possible DNA impurities were discussed in the COVID-19 Comirnaty mRNA vaccine 2021 EMA assessment and also in June 2022 by physicians in an FDA meeting [123]. Then, DNA contamination was found in the mRNA vaccine vials in 2023 by K. McKernan (confirmed by others) (described in this preprint [124]). The 2022 Genentech study states, “Although modRNA poorly activates TLR7/8, it can have residual innate agonist properties…” and the article describes RNA contamination and other unwanted remaining uncapped messenger RNA or mRNA tertiary structures as potential agonist properties, stating, “any of which can be a source of signal 1...” (For reference: An agonist is described as “A substance which initiates a physiological response when combined with a receptor.” Oxford Dictionary.)

• Lipids- “Empty LNP (SM-102) particles on their own were sufficient for IL-1β release in vitro, suggesting that the lipids alone can provide both signals 1 and 2 for inflammasome activation.” [115]

29. Interleukin-1β, signal 1, signal 2, and inflammasome activation: “Interleukin-1β (IL-1β) is a potent pro-inflammatory cytokine that is crucial for host-defence responses to infection and injury…” [126] Inflammasome activation requires two types of signals. “The inflammasome is a multi-protein complex that mediates activation of caspase-1, which promotes the secretion of the proinflammatory cytokines IL-1β. [127] “IL-1 in turn triggers the induction of the broad spectrum of pro-inflammatory cytokines (including IL-6).” [115] “When inflammasomes are aberrantly activated [this] can drive excessive production of pro-inflammatory cytokines and cell death, leading to tissue damage.” [125]

30. Both pre-pandemic liposome, lipid, and LNPs are linked to IL-1β secretion and inflammasome activation: The “similar” lipids to the Pfizer lipids, used in Onpattro, which was approved in 2018, have warnings for lipid complement-activated adverse events; other pre-pandemic lipid and liposomal delivery drug adverse events are well represented in several years of medical studies and articles included herein. [28] Of interest, this 2013 study shows the inflammasome links to complement-mediated inflammation and IL-1β. It states. “…dysregulation of complement is critical to several autoimmune and inflammatory syndromes. Elevated expression of the proinflammatory cytokine IL-1β is often linked to such diseases. In this study, we reveal the mechanistic link between complement and IL-1β secretion... IL-1β secretion occurs following intracellular caspase-1 activation by inflammasomes. [116] “Understanding of inflammasome pathways may provide insights into disease pathogenesis that might serve as potential targets for therapeutic intervention.” [127]

31. In closing, pre-pandemic studies warned that PEG and lipid alternatives should be considered; why weren’t these warnings considered? Again, mRNA and lipid-shell drugs and their gene therapy iterations struggled to meet safety standards to gain approval for use for over 20 years. The latest attempt before the COVID-19 mRNA therapies was Onpattro, the drug with “similar lipids” to the COVID-19 mRNA vaccine lipids. Onpattro requires premedication upon administration to this day --due to the toxicity of the lipids—per the FDA patient sheet. [3]

This pre-pandemic potential for lipid toxicity did not stop taking place in COVID-19 mRNA vaccines, and despite any modifications, the current adverse events and immune dysregulation are seen in studies herein. In fact, these COVID-19 vaccine adverse events must step forward until common knowledge of these issues takes place and an understanding as to why many studies suggest alternatives to the use of lipids and PEG in medicine and therapies occurs.

Again, of importance, in this study co-authored by LNP co-developer Peter Cullis, published just months before the COVID-19 vaccine rollout, which shows unpredictability and safety issues with the LNPs, it states, “This emphasizes, once more, that the “one size fits all” nanomedicine approach should be replaced with a more personalized framework...” [72]

Why were consumers not specifically told of the pre-pandemic adverse events known to the similar lipids? Why weren’t signals seen in animal studies?

These questions are addressed in the 90-page accompanying Executive Summary ( the summary has also been updated in November 2023, and I will begin re-posting it in the following weeks) to this brief, including the referenced studies, pre-pandemic and post-vaccine articles, and accompanying health official, vaccine, and LNP developer statements found in pre and post-vaccine articles. 

---

About the author: Many may know me from my public speaking or from Cody’s story. I am the mother of Cody Hudson, who has a published medical case study and was significantly vaccine-injured at age 21.  My research on the COVID-19 vaccine LNP has been published and is used in investigations into the COVID-19 mRNA vaccines. I write to bring awareness to these issues as I care for Cody.  Please consider contributing to support my work or to help with his medical and educational expenses. Thank you.

~Some may not know that Cody was hospitalized in October and November, and I am catching up with my writing and thanking all who prayed and have been supportive; I thank everyone for their kindness. Cody is making a video this week to thank everyone himself. He will have his blood clotting disorder for life, but he is making strides in getting stronger after having DVTs in all four limbs recently.~

---

The writer is not a doctor, and even though guest writers may be medical professionals, the information in this document and this publication is not a substitution for personal or individual medical care, treatment, medical advice, or diagnosis. Always contact your own medical care provider for individual care and consultation. This document does not diagnose medical conditions, treat illnesses, or prescribe medicine or drugs. Any information contained in this document, related links, or attachments is not a substitute for seeking adequate medical care, diagnosis, and/or treatment from your own medical doctor.

---

References- The following references belong to the LNP timeline, the Executive Brief, and the Executive Summary:

2. Project Veritas, March 16, 2023, BREAKING: “Confidential Pfizer Documents Reveal Pharmaceutical Giant Had ‘Evidence’ Suggesting ‘Increased Risk of Myocarditis’ Following COVID-19 Vaccinations in Early 2022,”

https://www.projectveritas.com/news/breaking-confidential-pfizer-documents-reveal-pharmaceutical-giant-had/

3. EMA documents assessments report Onpattro 2018  https://www.ema.europa.eu/en/documents/assessment-report/onpattro-epar-public-assessment-report_.pdf

6. Jop de Vrieze, Science Insider Health- 21 Dec 2020: “Suspicions grow that nanoparticles in Pfizer's COVID-19 vaccine trigger rare allergic reactions. Life-threatening responses seen in at least eight people could be linked to polyethylene glycol, known to trigger reactions to some drugs” https://www.science.org/content/article/suspicions-grow-nanoparticles-pfizer-s-covid-19-vaccine-trigger-rare-allergic-reactions

9. Szebeni, J., Simberg, D., González-Fernández, Á. et al. Roadmap and strategy for overcoming infusion reactions to nanomedicines. Nature Nanotech 13, 1100–1108 (2018). https://doi.org/10.1038/s41565-018-0273-1

11. Peter Cullis, Cell: Leading Edge Conversations: Learning lessons from lipids to make COVID-19 vaccines- April 2022-  http://www.liposomes.ca/publications/2020s/Cullis%202022%20-%20Learning%20lessons%20from%20lipids%20to%20make%20COVID-19%20vaccines.pdf

12. Ryan Cross, Chemical and Engineering News article, March 6, 2021, “Without these lipid shells, there would be no mRNA vaccines for COVID-19- Fragile mRNA molecules used in COVID-19 vaccines can’t get into cells on their own. They owe their success to lipid nanoparticles that took decades to refine https://cen.acs.org/pharmaceuticals/drug-delivery/Without-lipid-shells-mRNA-vaccines/99/i8

23. Damian Garde, Jan. 10, 2017, Lavishly funded Moderna hits safety problems in bold bid to revolutionize medicine https://www.statnews.com/2017/01/10/moderna-trouble-mrna/

27. Nakamura Y, Mochida A, Choyke PL, Kobayashi H. Nanodrug Delivery: Is the Enhanced Permeability and Retention Effect Sufficient for Curing Cancer? Bioconjug Chem. 2016 Oct 19;27(10):2225-2238. doi: 10.1021/acs.bioconjchem.6b00437. Epub 2016 Sep 2. PMID: 27547843; PMCID: PMC7397928. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397928/        

28. Dézsi L, Mészáros T, Kozma G, H-Velkei M, Oláh CZ, Szabó M, Patkó Z, Fülöp T, Hennies M, Szebeni M, Barta BA, Merkely B, Radovits T, Szebeni J. A naturally hypersensitive porcine model may help understand the mechanism of COVID-19 mRNA vaccine-induced rare (pseudo) allergic reactions: complement activation as a possible contributing factor. Geroscience. 2022 Apr;44(2):597-618. doi: 10.1007/s11357-021-00495-y. Epub 2022 Feb 11. PMID: 35146583; PMCID: PMC8831099.

30. Desai, N. Challenges in Development of Nanoparticle-Based Therapeutics. AAPS J 14, 282–295 (2012). https://doi.org/10.1208/s12248-012-9339-4 https://link.springer.com/article/10.1208/s12248-012-9339-4

44. BNT162b2 Module 2.6.4. Pharmacokinetics Written Summary https://phmpt.org/wp-content/uploads/2022/03/125742_S1_M2_26_pharmkin-written-summary.pdf

53. Molina-Rios, S., Rojas-Martinez, R., Estévez-Ramirez, G. M., & Medina, Y. F. (2023). Systemic lupus erythematosus and antiphospholipid syndrome after COVID-19 vaccination. A case report. Modern Rheumatology Case Reports, 7(1), 43-46. https://pubmed.ncbi.nlm.nih.gov/35246682/

54. Fu, P. A., Chen, C. W., Hsu, Y. T., Wei, K. C., Lin, P. C., & Chen, T. Y. (2022). A case of acquired hemophilia A and bullous pemphigoid following SARS-CoV-2 mRNA vaccination. Journal of the Formosan Medical Association, 121(9), 1872-1876. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8919791/

55. Báez-Negrón, L., & Vilá, L. M. (2022). New-onset systemic lupus erythematosus after mRNA SARS-CoV-2 vaccination. Case Reports in Rheumatology, 2022. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8856802/

56. Balbona, E. J. (2023). A Case of COVID MRNA Vaccine Linked Antiphospholipid Syndrome. Biomed Sci Clin Res, 2(1), 159-161. https://www.opastpublishers.com/open-access-articles/a-case-of-covid-mrna-vaccine-linked-antiphospholipid-syndrome.pdf

57. Alqatari S, Ismail M, Hasan M, Bukhari R, Al Argan R, Alwaheed A, Alkhafaji D, Ahmed SE, Hadhiah K, Alamri T, Nemer A, Albeladi F, Bumurah NN, Sharofna K, Albaggal Z, Alghamdi R, AlSulaiman RS. Emergence of Post COVID-19 Vaccine Autoimmune Diseases: A Single Center Study. Infect Drug Resist. 2023 Mar 4;16:1263-1278. doi: 10.2147/IDR.S394602. PMID: 36910517; PMCID: PMC9994665.

58. Norbert Pardi, Steven Tuyishime, Hiromi Muramatsu, Katalin Kariko, Barbara L. Mui, Ying K. Tam, Thomas D. Madden, Michael J. Hope, Drew Weissman Expression kinetics of nucleoside-modified mRNA delivered in lipid nanoparticles to mice by various routes August 2015, Journal of Controlled Release PII: S0168-3659(15)30053-5DOI: doi: 10.1016/j.jconrel.2015.08.007 https://www.researchgate.net/publication/280997102_Expression_kinetics_of_nucleoside-modified_mRNA_delivered_in_lipid_nanoparticles_to_mice_by_various_routes Also https://www.sciencedirect.com/science/article/abs/pii/S0168365915300535?via%3Dihub

63. Vlatkovic, Irena Scholarly JournalNon-Immunotherapy Application of LNP-mRNA: Maximizing Efficacy and Safety/ Biomedicines; Basel Vol. 9, Iss. 5,  (2021): 530. DOI:10.3390/biomedicines9050530

66. The FDA Full EUA for Pfizer mRNA-LNP Covid-19 vaccine https://www.fda.gov/media/144416/download

67. Full EMA report Comirnaty Covid-19 vaccine https://www.ema.europa.eu/en/documents/assessment-report/comirnaty-epar-public-assessment-report_en.pdf

72. Valentina Francia, Raymond M. Schiffelers, Pieter R. Cullis, and Dominik Witzigmann / The Biomolecular Corona of Lipid Nanoparticles for Gene Therapy/ Bioconjugate Chemistry 2020 31 (9), 2046-2059 DOI: 10.1021/acs.bioconjchem.0c00366

75. Pfizer/ A Tissue Distribution Study of a [3 H]-Labelled Lipid Nanoparticle-mRNA Formulation Containing ALC-0315 and ALC-0159 Following Intramuscular Administration in Wistar Han Rats https://phmpt.org/wp-content/uploads/2022/03/125742_S1_M4_4223_185350.pdf

78. FDA EUA Development and Licensure of Vaccines to Prevent COVID-19 https://www.fda.gov/media/139638/download

79. Morteza Mahmoudi Mol. Pharmaceutics 2021, 18, 2, 476–482 Emerging Biomolecular Testing to Assess the Risk of Mortality from COVID-19 Infection Publication Date: May 7, 2020,  https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.0c00371

81. Fülöp T, Mészáros T, Kozma GT, Szebeni J, Józsi M. Infusion Reactions Associated with the Medical Application of Monoclonal Antibodies: The Role of Complement Activation and Possibility of Inhibition by Factor H. Antibodies (Basel). 2018 Mar 14;7(1):14. doi: 10.3390/antib7010014. PMID: 31544866; PMCID: PMC6698840. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6698840/#B1-antibodies-07-00014

86. Kong Yi Wen, Dreaden Erik C “PEG: Will It Come Back to You? Polyethylene Glycol Immunogenicity, COVID Vaccines, and the Case for New PEG Derivatives and Alternatives”  Frontiers in Bioengineering and Biotechnology VOLUME 10 /2022/  URL=https://www.frontiersin.org/articles/10.3389/fbioe.2022.879988 

91. Abe N, Bohgaki M, Kasahara H. SARS-CoV-2 mRNA Vaccination-induced Autoimmune Polyarthritis-like Rheumatoid Arthritis. Mayo Clin Proc. 2022 Aug;97(8):1574-1575. doi: 10.1016/j.mayocp.2022.06.001. Epub 2022 Jun 8. PMID: 35933141; PMCID: PMC9174152. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9174152/

93. McSweeney MD, Versfeld ZC, Carpenter DM, Lai SK. Physician Awareness of Immune Responses to Polyethylene Glycol-Drug Conjugates. Clin Transl Sci. 2018 Mar;11(2):162-165. doi: 10.1111/cts.12537. Epub 2018 Jan 31. PMID: 29383836; PMCID: PMC5866984.

94. László Dézsi, Gábor Szénási, Rudolf Urbanics, László Rosivall, János Szebeni - Cardiopulmonary and hemodynamic changes in complement activation-related pseudoallergy Vol.5 No.6(2013), Article ID:32888,7 pages DOI:10.4236/health.2013.56138 https://www.scirp.org/html/11-8202090_32888.htm

95. Keith Peden- Laboratory of DNA Viruses Division of Viral Products Office of Vaccines Research and Review CBER/FDA “Considerations for the Quality, Safety and Efficacy of Prophylactic Lipid Nanoparticle mRNA Vaccines” https://www.fda.gov/media/166986/download

99. Table- Annex 1 EMA Onpattro Assessment Summary of product Characteristics/ July 2018, https://www.ema.europa.eu/en/documents/product-information/onpattro-epar-product-information_en.pdf

100.  Zhang X, Goel V, Attar Wala H, Sweetser MT, Clausen VA, Robbie GJ. Patisiran Pharmacokinetics, Pharmacodynamics, and Exposure-Response Analyses in the Phase 3 APOLLO Trial in Patients With Hereditary Transthyretin-Mediated (hatter) Amyloidosis. J Clin Pharmacol. 2020 Jan;60(1):37-49. doi: 10.1002/jcph.1480 Epub 2019 Jul 19. PMID: 31322739; PMCID: PMC6972979.

101. American Cancer Society - What are Infusion or Immune Reactions?

https://www.cancer.org/cancer/managing-cancer/side-effects/infusion-immune-reactions/what-are-infusion-immune-reactions.html

110. Anis Barmada et al., Cytokinopathy with aberrant cytotoxic lymphocytes and profibrotic myeloid response in SARS-CoV-2 mRNA vaccine–associated myocarditis. Sci. Immunol. 8, eadh3455(2023). DOI:10.1126/sciimmunol.adh3455 https://www.science.org/doi/10.1126/sciimmunol.adh3455

115. Tahtinen, S., Tong, AJ., Himmels, P. et al. IL-1 and IL-1ra are key regulators of the inflammatory response to RNA vaccines. Nat Immunol 23, 532–542 (2022). https://doi.org/10.1038/s41590-022-01160-y

116. Federica Laudisi, Roberto Spreafico, Maximilien Evrard, Timothy R. Hughes, Barbara Mandriani, Matheswaran Kandasamy, B. Paul Morgan, Baalasubramanian Sivasankar, Alessandra Mortellaro; Cutting Edge: The NLRP3 Inflammasome Links Complement-Mediated Inflammation and IL-1β Release. J Immunol 1 August 2013; 191 (3): 1006–1010. https://doi.org/10.4049/jimmunol.1300489

117. PF-07302048 BNT162 RNA Based COVID Vaccines Internal Document April 2022: https://selfreliancecentral.com/wp-content/uploads/2023/07/nejmoa2034577_protocol.pdf

118. The Nobel Prize in Physiology or Medicine 2023 Discoveries concerning nucleoside base modifications that enabled the development of effective mRNA vaccines against COVID-19 (pdf)

119. Pedro Morais, Hironori Adachi, Yi-Tao Yu The Critical Contribution of Pseudouridine to mRNA COVID-19 Vaccines Front. Cell Dev. Biol., 04 November 2021 Sec. Epigenomics and Epigenetics https://www.frontiersin.org/articles/10.3389/fcell.2021.789427/full

120. Biykem Bozkurt Shedding Light on Mechanisms of Myocarditis With COVID-19 mRNA Vaccines published 16 Feb 2023 Circulation. 2023;147:877–880 https://doi.org/10.1161/CIRCULATIONAHA.123.063396

121. Penn State - Paving the Way for a COVID-19 Vaccine: A Conversation with Dr. Drew Weissman Friday, December 11, 2020, https://www.pennmedicine.org/coronavirus/vaccine/qa-with-drew-weissman

122. Bella Isaacs-Thomas, PBS NEWS HOUR The powerful technology behind the Pfizer and Moderna vaccines Health Apr 2, 2021, 6:44 PM EST https://www.pbs.org/newshour/health/the-powerful-technology-behind-the-pfizer-and-moderna-vaccines

123. FDA- CTGTAC Meeting June 10th 2022 FDA-2022-N-0470 https://www.fda.gov/advisory-committees/advisory-committee-calendar/cellular-tissue-and-gene-therapies-advisory-committee-june-9-10-2022-meeting-announcement-06092022

124. McKernan, Kevin, Yvonne Helbert, Liam T. Kane, and Stephen McLaughlin. 2023. “Sequencing of Bivalent Moderna and Pfizer mRNA Vaccines Reveals Nanogram to Microgram Quantities of Expression Vector Dsdna Per Dose.” OSF Preprints. April 10. doi:10.31219/osf.io/b9t7m. https://osf.io/b9t7m/

125. Samuel Lara-Reyna, Emily A Caseley, Joanne Topping, François Rodrigues, Jorge Jimenez Macias, Sean E Lawler, Michael F McDermott Inflammasome activation: from molecular mechanisms to autoinflammation published: 07 July 2022 https://doi.org/10.1002/cti2.1404

126. Lopez-Castejon G, Brough D. Understanding the mechanism of IL-1β secretion. Cytokine Growth Factor Rev. 2011 Aug;22(4):189-95. DOI: 10.1016/j.cytogfr.2011.10.001. Epub 2011 Oct 22. PMID: 22019906

127. Franchi L, Eigenbrod T, Muñoz-Planillo R, Nuñez G. The inflammasome: a caspase-1-activation platform that regulates immune responses and disease pathogenesis. Nat Immunol. 2009 Mar;10(3):241-7. doi: 10.1038/ni.1703. PMID: 19221555; PMCID: PMC2820724.

128. Oscar L. Volger, Chapter 3.3 - ’Omics-Based Testing for Direct Immunotoxicity, Editor(s): Jos Kleinjans,

https://www.sciencedirect.com/science/article/pii/B9780123978622000061.

129. Nikhil Ranjan, Molly Kuzma, Xiang-Zuo Pan, Michael Cole, Robert A. Brodsky, Gloria F. Gerber,

Sars-Cov-2 Spike Protein Triggers Inflammasome-Mediated Tissue Factor Activity, Blood, Volume 142, Supplement 1, 2023, Page 5405, ISSN 0006-4971, https://doi.org/10.1182/blood-2023-187738.

130. NOVAVAX/ SERUM INSTITUTE OF INDIA (SII) COVID-19 VACCINE

Oscar L. Volger, Chapter 3.3 - ’Omics-Based Testing for Direct https://covid-19pharmacovigilance.paho.org/novavax-serum-institute-of-india-sii