Part 3 of 10- The alarming pre-pandemic LNP history Covid-19 vaccine developers likely won't want you to see -studies dating back 20 years: Executive Summary sent to lawmakers & state investigators.
History of lipid adverse events, autoimmune reports, and eye-opening Katalin Kariko, Drew Weissman, and Peter Cullis mRNA and LNP development studies: Executive Summary. These are The LNP Files...
Below is part 3 of 10 of the Executive Summary on Sars-CoV-2 mRNA Vaccine Lipid Nanoparticles (LNPs). The studies utilized, referenced, and quoted in this series include medical studies and articles mainly written or co-written by the developers of the COVID-19 mRNA vaccine LNPs and mRNA technology. These studies date back twenty years. The drug manufacturer data and studies are included along with Pfizer’s internal white paper, which is relevant to the LNPs and lipid development. * Parts one and two of this series are found in my SubStack. * References are found on the last page/article in this series of Ten Articles. *Please credit my work and link to this source if you repost any part of my work. Thank You *
Heather Hudson May 2023 - Part 3 of 10
C. Introduction to Biodistribution, Pharmacokinetics, and non-clinical studies, their importance in drug safety and adverse events; and an introduction to the two significant pre-pandemic LNP development studies co-authored by the co-creators of the Pfizer Covid-19 mRNA-LNP vaccines:
1. Please note that non-clinical studies include animal studies and studies not performed on humans. Clinical studies are human studies.
2. The 2020 FDA EUA Guidelines for the Development and Licensure of Vaccines to Prevent COVID-19 states, “Biodistribution studies in an animal species should be considered if the vaccine construct is novel in nature and there are no existing biodistribution data from the platform technology. These studies should be conducted if there is a likelihood of altered infectivity and tissue tropism or if a novel route of administration and formulation is to be used.”[78] [Referenced is the FDA document which provides the guidelines set out in the EUA for manufacturers to obtain approval for Covid-19 vaccines.]
3. Previous to these guidelines, in 2007, similar guidelines can be found in the FDA Guidance for Industry Considerations for Plasmid DNA Vaccines for Infectious Disease Indications, which states, “: Biodistribution studies will still be necessary for DNA vaccines utilizing novel vectors, formulations, methods of delivery, routes of administration, or any other modifications expected to significantly impact cellular uptake and/or biodistribution...” [64-Pg 8]
4. Biodistribution and pharmacokinetics of the LNPs and mRNA: Biodistribution studies and pharmacokinetics studies describe the length of time a formulation or drug circulates and remains in the organs/body. They also include information describing where the drug or formulation travels to (or distributes to) and how long it remains in the body and more, as seen in these studies: [27][28][29][30][49].
5. Important information on the need for biodistribution, pharmacokinetics, and more:” Here, this 2018 study called, Toxicology and Biodistribution: The Clinical Value of Animal Biodistribution Studies,” states, “Because the objective of these studies is to produce information assuring safe administration of the investigational product to humans, the test systems, either in vivo or in vitro, need to be relevant to the human situation, and strategies for human translation of the studies’ outcomes are fundamental. The choice of human-relevant test systems is, therefore, a fundamental piece for safe and effective development of any molecule. The relevance of the test systems, either in vitro or in vivo, is based on the similarity of the pharmacology, pharmacodynamics, physiology, biochemistry, target biology, cellular cascades, kinetics, tissue responses, etc. When animal models are used, it is fundamental to understand how those aspects apply to humans...” [49]
6. In discussing the Covid-19 mRNA-LNP vaccine’s biodistribution and pre-clinical/animal studies, it should be said that the following three names (and their roles and relationships) are seen often in animal studies and studies used in the development of the Covid-19 mRNA-LNP vaccines as follows:
Peter Cullis (co-founder of Acuitas Therapeutics), Katalin Kariko (Senior VP of BioNTech), and Drew Weissman (co-developer of the mRNA technologies in the Covid-19 vaccines) are seen in studies they have written and co-authored that are referenced within this Executive Summary.
1997: Katalin Kariko and Drew Weissman worked together in developing the mRNA technology, as well as they are seen in studies testing mRNA-LNP formulation.
2009: Acuitas Therapeutics is Co-Founded by Peter Cullis.
2015: The “Expression Kinetics” study (discussed just below) was co-authored by Katalin Kariko and Drew Weissman (along with four scientists from Acuitas Therapeutics and two other authors).
2018: Peter Cullis/ Acuitas Therapeutics, Katalin Kariko, and Drew Weissman worked together to develop the LNPs used in the Covid-19 mRNA-LNP vaccines.[11]
August 2020: The “Biomolecular Corona” study (discussed below) was co-authored by Peter Cullis.
Beginning July 2020 and approved November 2020: Acuitas Therapeutics “Sponsored’ the Pfizer Covid-19 mRNA-LNP vaccine EUA Wistar Rat Study, called “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;” for the Pfizer FDA EUA.
For the non-clinical studies, a “Sponsor” is a person who takes responsibility for and initiates a clinical investigation. The sponsor may be an individual or pharmaceutical company, governmental agency, academic institution, private organization, or other organization,…” per Federal Food, Drug, and Cosmetic Act (secs. 201–902, 52 Stat. 1040 et seq., as amended (21 U.S.C. 301–392))
7. Covid-19 mRNA-LNP Vaccines Biodistribution Studies and FDA Approval: In the 2020 FDA “Pfizer-BioNTech COVID-19 Vaccine VRBPAC Briefing Document” regarding their FDA EUA approval and biodistribution studies, Pfizer provides “The key nonclinical studies supporting the EUA of BNT162b2 administered twice by IM injection at a dose of 30 g RNA…” Noteworthy in their statement is that Pfizer understands that the biodistribution studies support their application for FDA EUA approval. [73] Factors that may alter, vary, or obscure these studies should be made known to the FDA, the consumer, and providers. As seen in the 2018 article called “Toxicology and Biodistribution, which states, “Because the objective of these studies is to produce information assuring safe administration of the investigational product to humans, the test systems, either in vivo or in vitro, need to be relevant to the human situation, and strategies for human translation of the studies’ outcomes are fundamental.”[49]
D. Pre-Pandemic Biodistribution Studies Provide Information –But Covid-19 mRNA Vaccine Consumers Never Saw It: In a 2015 animal study called “Expression Kinetics,” co-authored by a Senior V.P. of BioNTech Katalin Kariko and Drew Weissman (Developers for the Pfizer Covid-19 mRNA, along with four scientists from Acuitas Therapeutics (developers of the Covid-19 mRNA-LNP vaccines) and two other authors, the study describes that the depth of the injection in the muscle for intramuscular mRNA-LNP formulations determines the organs/locations that the drug formula distributes to in the body, the amount of formula that is distributed to the location, and the length of time it remains in the body, as seen below:
a. “Here, we show that in vivo administration of mRNA-LNP complexes by various commonly used injection routes displays different expression patterns and kinetics. Depending on the site of injection, both local protein production and dissemination to the liver occurs. Interestingly, we observed that 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). Importantly, very low doses (0.005 mg/kg) of mRNA-LNPs could be translated for several days following the tested delivery routes demonstrating the potential of these formulations for in vivo development.” [58]
b. The study shows that the location of the LNP injection (i.e. intramuscular, subcutaneous, or intratracheal) and, especially, the depth of the injection into the muscle is shown to determine crucial outcomes as to where the LNPs (and mRNA) distribute in the body and organs. It also determines how much LNP (and mRNA) is distributed (into each location in the body and organs) and the amount of time the LNP remains in the body and organs.
c. Per the FDA, these factors are called biodistribution and pharmacokinetics. Their outcomes are used to determine safety and efficacy. They factor in the approval of a drug, even an EUA drug. In short, the “Expression Kinetics” animal study shows that the biodistribution and pharmacokinetics of LNP-mRNA formulations are variable and (for administration into the muscle) dependent on the depth of injection. [58]
d. The “Expression Kinetics” study also states, “Intramuscular (deep) and intratracheal delivery resulted in protein production both in the liver and at the injection sites… Protein production for intramuscular delivery, especially superficial injection, in the muscle could be measured for up to 8 days and high amounts of protein was made…” [58]
e. After reading about the Expression kinetics study, now consider the 2020 Wistar Han Rat Studies completed for the Pfizer Covid-19 mRNA-LNP vaccines, in which this information about the depth of the injection in the muscle is not given in the study or in any of the pre-clinical studies utilized in the Pfizer FDA EUA application or patient and provider information.
f. As we are told above in this study that the distribution and other outcomes of these mRNA-LNP studies are dependent upon the administration/injection site, and in the case of muscular injections (or intramuscular injections) –the outcome is dependent on the depth of the injection. [58] The details on the depth of injections given to the animals in the 2020 Pfizer pre-clinical animal models are not seen in the Pfizer Covid-19 mRNA vaccine studies provided to the FDA for Emergency Use Authorization (and later seen by consumers via FOIA). Without knowing or documenting the depth of the intramuscular injections of the mice/animals in the Covid-19 vaccine animal studies (as was done in the 2015 “Expression Kinetics” LNP-mRNA mouse study), the outcomes and variables of the Covid-19 LNP-mRNA vaccine animal models are missing these material factors that are shown to affect the outcome of LNP-mRNA mouse/animal biodistribution and safety studies. [58]
g. Please keep in mind that we are shown in the biodistribution studies, that the LNP is meant to protect the mRNA as it travels in the body, it “carries” the mRNA (and the mRNA-LNP drugs are called LNP “carrier drugs”), and the LNP is found in the biodistribution into the liver and more for this reason. For example, in this 2021 study called, “Lipid nanoparticles for mRNA delivery, “ In addition to cationic or ionizable lipids, lipid nanoparticle–mRNA formulations typically contain other lipid components, such as phospholipids (for example, phosphatidylcholine and phosphatidylethanolamine), cholesterol or polyethylene glycol (PEG)-functionalized lipids (PEG-lipids)… These lipids can improve nanoparticle properties, such as particle stability, delivery efficacy, tolerability, and biodistribution.” [39][43]
h. Of importance, the provided FDA EUA patient fact sheet information, and instructions on the administration of the Covid-19 mRNA-LNP vaccine injection in the Pfizer and Moderna Covid-19 vaccines show that practitioners and providers of Covid-19 mRNA vaccines were not given details on this vital “Expression Kinetics” study information on the depth of the intramuscular injection’s ability to alter mRNA-LNP drug delivery biodistribution and more. [25]
i. The “Expression Kinetics” study is discussed throughout this summary due to its importance: This vaccine administration information in the “Expression Kinetics” study was not included in the Pfizer FDA EUA Dosing and Administration instructions for medical providers. It was not mentioned in the biodistribution studies. However, the FDA guidelines for the novel Covid-19 EUA vaccine applicants, “Development and Licensure of Vaccines to Prevent COVID-19,” shows the importance of the route of administration and possibility for tissue tropism and more, as seen here where it states, “These studies should be conducted if there is a likelihood of altered infectivity and tissue tropism or if a novel route of administration and formulation is to be used.” [78]
j. In biomedicine, according to the studies, cell tropism (tissue tropism) is altered or “enhanced” by the use of LNPs. Modifying the outcome of the LNPs also modifies tissue tropism or “cellular uptake” as seen here in the 2015 “Expression Kinetics” study which revealed that the variable depth of intramuscular route of administration for the mRNA-LNP formulation describe a modification of the mRNA-LNP delivery with an ability to impact cellular uptake and biodistribution. Yet, the importance and contents of this mRNA-LNP study are absent in Pfizer’s FDA EUA Covid-19 mRNA-LNP vaccine application and data. [58]
k. As further evidence and understanding of these studies, this 2018 article co-written by Drew Weissman (co-developer of the Pfizer Covid-19 vaccines), entitled, “mRNA vaccines — a new era in vaccinology” states, “The magnitude and duration of in vivo protein production from mRNA–LNP vaccines can be controlled in part by varying the route of administration. Intramuscular and intradermal delivery of mRNA–LNPs has been shown to result in more persistent protein expression than systemic delivery routes...” [107] This information was not given to the consumer, and as we see here from item “a.” above, in the Expression Kinetics study, this information affects both the mRNA and the LNP “Importantly, very low doses (0.005 mg/kg) of mRNA-LNPs could be translated for several days following the tested delivery routes demonstrating the potential of these formulations for in vivo development.”
Were consumers told, and was the FDA told, that a study co-authored by parties that co-created the LNPs used in the Covid-19 mRNA-LNP vaccines --called the “Expression Kinetics” study (written about mRNA-LNP kinetics) reveals that LNP biodistribution (and more) are significantly variable and are able to be significantly changed/manipulated via parameters of the injection/administration of the drug into the muscle?
Diagram 1. shows depth of muscle injection described in the alternating biodistribution seen in the differing locations and the depth of muscle injection (superficial or deep). Corresponding study and medical data can be found in the Expression Kinetics study. [58]
E. The “Biomolecular Corona” LNP study published three months before the Pfizer FDA EUA pre-clinical animal studies approvals; “additional key study”: Equally as important to the “Expression Kinetics” studies is the “Biomolecular Corona” study. This study states, “the biomolecular corona can be seen as an LNP surface modification: it can affect [LNP] particle physicochemical characteristics … and therefore stability, blood residency, biodistribution, immune system recognition, and cell binding… and targeting…” The study also states, “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]
Of importance: This study is co-written by the Co-Founder of Acuitas Therapeutics, Peter Cullis. During the time this study was written, Peter Cullis worked with the Senior VP of BioNTech, Katalin Kariko, and Covid-19 mRNA Vaccine Developer, Drew Weissman, to develop the LNPs used for the Pfizer Covid-19 mRNA vaccine. [11] The Pfizer animal studies were also being conducted during this timeframe as well. [73]
“The Biomolecular Corona of Lipid Nanoparticles for Gene Therapy” study discusses LNP biodistribution and more. [72] This Biomolecular Corona study was Published on August 7th, 2020 (three months before the Covid-19 vaccines were approved under the FDA EUA). Peter Cullis co-authored this “Biomolecular Corona” study.
Peter Cullis is also the co-founder of Acuitas Therapeutics which “Sponsored’ the Pfizer Covid-19 mRNA-LNP vaccine EUA- Weister Rat Bio Distribution Study, called “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;” This Acuitas pre-clinical rat study was completed 24 September 2020 and was approved November 9th, 2020, according to the study. [73]
The importance of the findings of the “Biomolecular Corona” study should be noted while reading the Pfizer FDA EUA biodistribution studies and all other Pfizer FDA EUA studies and documents referenced within this Executive Summary. Keeping in mind that the FDA guidelines for the novel COVID-19 EUA vaccine applicants, “Development and Licensure of Vaccines to Prevent COVID-19,” states, “Biodistribution studies in an animal species should be considered if the vaccine construct is novel in nature and there are no existing biodistribution data from the platform technology. These studies should be conducted if there is a likelihood of altered infectivity and tissue tropism or if a novel route of administration and formulation is to be used. More details are found below as follows:
1. “The Biomolecular Corona” study then discusses the adverse reactions known to PEG and PEGylated lipids as seen here, stating, “LNPs and the biological environment strongly affect corona composition,” further, it states, “In addition to the interference with cellular interactions, PEG can generate unwanted adverse effects such as complement activation, which may result in hypersensitivity reactions… and even anaphylaxis… PEGylation can trigger the production of antibodies that preclude the possibility of repetitive administrations…” [72]
2. Continued: In addition, regarding LNPs, this article states, “Several examples… that show that the corona plays a fundamental role in tissue-selective targeting and that the particle chemical identity is not sufficient to describe the complex transformations and interactions happening in vivo. By the time they reach target cells, LNPs have been in contact with hundreds of biomolecules and barriers, which inevitably alter their chemical nature. Thus, at this point, the biologically relevant entity is no longer the bare particle, but rather a nanoobject with a distinct size, charge, shape, and biomolecular corona. The relevance given to the biological identity of LNPs comes from the observation that the corona alters the physicochemical properties of LNPs… and thus their stability,… integrity, release profile… biodistribution,… and targeting capability…. As a consequence, LNP development must not disregard the effect of the biological environment during LNP delivery.” [72]
3. The article continues, “Understanding how to engineer LNPs to selectively target tissues beyond the liver will be key to develop next-generation gene therapies. High-throughput screenings are powerful tools that could reveal the correlation between LNP composition and biodistribution…” [72] This statement appears to inform that understanding/developing LNP biodistribution (beyond the liver) had not been achieved and that the correlation between LNP composition and biodistribution is not revealed/understood as of the date of the article’s publication (three months before the Pfizer FDA EUA approval).
4. The above information in this “Biomolecular Corona” study, especially this statement “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” and this statement, “the physicochemical characteristics of LNPs change upon corona formation, which is specific to the biological environment in which particles are administered” (amongst others) indicates that the LNPs experience unpredictable changes in differing biological environments. The differing biological environments described above would include the animals utilized in the biodistribution studies and pre-clinical biodistribution studies submitted in the FDA EUA for the LNP drugs to gain EUA authorization as found in the FDA’s Guidelines, “Development and Licensure of Vaccines to Prevent COVID-19.” [78] These biological environments would also include the people in the clinical studies and the consumers of the Covid-19 mRNA-LNP Covid-19 vaccines.
5. The variable LNP biodistribution and target tissue outcomes revealed in this “Biomolecular Corona” study (and the similar LNP corona studies below) and in the “Expression Kinetics” study may have been observed in the Pfizer November 2020, Wistar Han Rat studies. In July 2020, the LNP Wistar Han Rats studies for the Pfizer Covid-19 mRNA-LNP vaccine began and were “sponsored” by Acuitas labs, Study No. 185350. [73]
6. They were completed on November 9th, 2020, but are not included in the Pfizer-BioNTech Covid-19 Vaccine (BNT162, PF-07302048) Vaccines and Related Biological Products Advisory Committee Briefing Document Meetings December 10th, 2020. On page 12 of this study, it states: “The key nonclinical studies supporting the EUA of BNT162b2 administered twice by IM injection at a dose of 30 µg RNA are outlined in Table 1.” The study numbers utilized do not include Study No. 185350.
7. Of note, the Pfizer 2020 Acuitas Labs pre-clinical Wistar Han Rat study began at one dosage level, and it was discontinued at this first dosage level, then, the study continued by cutting the dose level by half (which according to the study indicates an unpredicted outcome of the first dosage administered to the rats, as it required a phone call to the study sponsor for direction in the matter, and the dose was lowered by half). As seen in this animal study, Pfizer’s work with Acuitas to alter the nanoparticle for mRNA translation in the arm/muscle [11] reveals that the nanoparticle formula distributed past the muscle into the liver and other organs, lymph nodes and more (animal studies and biodistribution studies are found in sections “N”,”O”, “P”, “Q” “S” and “U” herein). The Pfizer Covid-19 mRNA-LNP vaccine did not stay in the muscle. The animal studies and reports presented also discuss biodistribution studies showing the formulations distributing into the liver and distributing through the body.
8. Please keep in mind that according to the “Biomolecular Corona” study, each biological environment (even the same environment over time) can present differing LNP outcomes “with potentially important implications for LNP clearance, target tissue accumulation, and efficacy”. [72]
9. Other studies on LNP Biomolecular Coronas (or Protein Coronas) such as this 2020 study which states, “Emerging Biomolecular Testing to Assess the Risk of Mortality from COVID-19 Infection” which 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]
10. Further, this 2022 Journal of Controlled Release article called “On the mechanism of tissue-selective gene delivery by lipid nanoparticles” states, “Although it has been reported that different endogenous factors may contribute to LNP tissue-tropism… our previous results and several reports by others showed that the high in vivo transfection efficiency was not directly correlated with biodistribution… which indicates that biodistribution alone cannot explain the selectivity of functional gene delivery.”
11. The biomolecular corona studies, the PEGylated LNP studies, the CARPA studies and the Expression Kinetics studies involve LNP biodistribution and other LNP drug safety and efficacy parameters. These studies and the medical literature (some co-authored by Pfizer mRNA and LNP developers), and documents within this Executive Summary present factors that highlight potential barriers to the Pfizer Covid-19 mRNA-LNP vaccine Biodistribution studies and studies that were utilized in determining the safety and more in the Pfizer Covid-19 mRNA vaccines. The Animal biodistribution studies are found in sections “N”,”O”, “P”, “Q” “S” and “U”.
12. Clearly adverse reactions that were not revealed in the Pfizer biodistribution studies are now evident, such as Myocarditis, autoimmune disorders, and anaphylaxis. [1][2][6][90][91][Autoimmune section below][See Table 1 in section Y]
13. Were consumers told, and was the FDA told, that studies on mRNA-LNP that show these factors are also variable due to the changes in LNP physical properties in each individual biological environment, and that the co-creator of the LNPs co-authored a study stating, “This emphasizes, once more, that the “one size fits all” nanomedicine approach should be replaced with a more personalized framework...”?
F. Covid-19 vaccine adverse reactions are linked to documented autoimmune disease: The significance of the “White Paper” above, the Expression Kinetics study and the Biomolecular Corona study presented just above, along with the medical journal articles referenced herein are prolific yet simply explained. Some adverse reactions that have been seen in the pre-pandemic (mostly) infused, similar lipid nano drugs of the past, including Onpattro, mirror the adverse reactions seen in the current Covid-19 vaccines.
1. Pfizer (in their internal white paper), the Australian government TGA, the Mayo clinic, physicians and scientist throughout the world have shown that these reactions are present in the Covid-19 mRNA-LNP vaccines. They are not disputed, and they can potentially elicit a complement or immune reaction, which can be fatal, life-altering, or have the potential to lead to autoimmune activation, as shown above in the White Paper, and by the Mayo clinic. [1][2][6][90][91]
2. Similar to the example of potential autoimmune myocarditis reaction shown by Pfizer in the Pfizer, internal 2022 White Paper (that was obtained by Project Veritas March 2023) [1][2], my own son suffered a near-fatal autoimmune reaction after his Covid-19 mRNA-LNP vaccine. At first, he had a reddened skin reaction that soon turned into lesions; he had pain in his leg, and then he suddenly had trouble breathing and began coughing blood; he was hospitalized with pulmonary embolism and thrombocytopenia; after thorough testing, his blood tests also revealed that his body had significant antibodies to the lipids in his Covid-19 mRNA vaccine, and he developed a life-threatening autoimmune blood clotting disorder. He also walks with a cane starting at age 22 due to the systemic nature of his reaction that is linked to the LNPs in his COVID-19 mRNA vaccine. He will likely suffer for life. Sadly, he is not alone; included are peer-reviewed examples of COVID-19 mRNA vaccine-linked autoimmune patient case studies.[53-57]
3. Please note that reference [57] includes thirty-one cases of new-onset autoimmune disorders after COVID-19 vaccines; twenty-nine of these cases were attributed to Pfizer, and one of these cases was reported as having a fatal outcome, per the study.
4. Then, in 2021, Nonclinical Evaluation Report by the TGA, the Australian government acknowledged the risk of autoimmune disease in the Pfizer Covid-19 mRNA-LNP vaccine, as seen here, in their report under “Immunotoxicity,” where it states, “No significant release of cytokines was observed in the repeat dose study with BNT162b2 variant V8, however, the number of animals studied for cytokines was small (n=3), and there was high inter animal variation. IFN-γ was increased in animals immunised with BNT162b2. IFN-γ has been found to play a role in autoimmunity (Lees 2015; Pollard et al. 2013). Thus, autoimmune diseases are a potential risk of the vaccine. This is addressable by the ongoing 2-year clinical studies.” [90]
5. LNP, lipid, or nano lipid complement-activated immediate adverse HSR reactions (anaphylactoid) are equally devastating as the potential autoimmune reactions as both can be fatal, and both can have life-altering outcomes, as shown in the case studies and peer-reviewed literature herein. According to the referenced studies, these adverse reactions can take place upon first exposure to the components without warning. CARPA reactions are a “pseudo allergy” that does not have a corresponding antigen test (as we are told by Szebeni et al. above and by others referenced below). Again, these adverse reactions can come about due to the properties of nanomedicine and its size, shape, and even curvature of the nanoparticle, as we are told by the medical references and studies in this document. [29][28][3][72] These studies show that the presence of the nanoparticles alone can bring about reactions that, sadly, can be fatal or nearly fatal, or minor. [14][57] But consumers were not warned of complement dysregulation and CARPA in the FDA EUA for the mRNA-LNP vaccines.
6. In the 2022 Pfizer internal White paper, the scientists express “well-known” vaccine-associated autoimmunity: This study states, “Vaccine-associated autoimmunity is a well-known phenomenon attributed most often to either the cross-reactivity between antigens or the effect of adjuvant. For example, HPV vaccine is linked to Guillain-Barre syndrome and other neuropathies (Watad et al, 2017). For COVID-19 mRNA vaccines, this matter becomes more complicated due to the nucleic acid formulation and presence of LNP as discussed above.” [2] These words in Pfizer’s internal White Paper bring about two questions, 1.) If these autoimmune reactions are “well known” to vaccines, why were the consumers not warned? 2.) If the nucleic acid and LNP complicates the matter of autoimmunity, in the ways mentioned “above” (“LNPs activate host immune response,” “pro-inflammatory” stimulation, immune responses “not fully understood”, and the biophysical features, size, shape… etc. “may also have an effect”), the consumer should have been warned, especially as the similar Onpattro lipids also showed autoimmune adverse events (at a “common” rate) as seen immediately below.
7. For Onpattro, looking at the Table 1. in the EMA assessment Annex 1 Summary of Product Characteristics, July 2018, shown in section Y, it can be seen that “Connective Tissue Disorders,” ”Arthralgias” are listed as “Common” on the chart/table of adverse events for this drug that Pfizer has notified as having similar lipids to the Covid-19 mRNA-LNP vaccines. [99] Note, per the Cleveland Clinic, “Connective tissue diseases include autoimmune diseases like rheumatoid arthritis, scleroderma and lupus.”
8. The parameters seen in the “Biomolecular Corona” studies [72] and the “Expression Kinetics” study [58] show that the LNPs can have different biodistribution and effects on toxicity and more, that was not explained to the consumer. A separate Biomolecular Corona study entitled “The impact of nanoparticle protein corona on cytotoxicity, immunotoxicity and target drug delivery” also states, “However, once injected in a physiological environment, NPs interact with biological components and are surrounded by a protein corona (PC). This can trigger an immune response and affect NP toxicity and targeting capabilities.” [83]
9. Other significant issues are seen with Nano Particles in animal studies and in other similar drugs as shown in the referenced material on coagulation [47] and in this Executive Summary in section R.
G: Relevant details on the similar lipid 2018 LNP Nano lipid carrier drug Onpattro and EMA data on immune stimulation, complement activation, special cautions, and adverse reactions:
The pre-pandemic approved LNP delivery drug Onpattro tells us more about the LNP complement system activation and immune responses (that can potentially lead to autoimmunity, serious adverse events, and mild adverse events in the Covid-19 mRNA vaccines), especially in the Pfizer Covid-19 mRNA vaccine, as Pfizer points us to look toward the LNP similarity. In Pfizer’s Internal White Paper which again states, “Pfizer Covid-19 mRNA vaccine, “Cholesterol and DSPC are naturally occurring lipids. ALC-0159 and ALC-0315 are similar to lipids (DLin-MC3-DMA and PEG2000-C-DMG) used in Onpattro (Patisiran).” [2] [For reference, ALC-0315 is an ionizable lipid that has been used to form lipid nanoparticles for the delivery of RNA. ALC-0159 is the PEGylated lipid, both are used in the Pfizer Covid-19 vaccine. The “naturally occurring” lipids, Cholesterol, and DSPC are the other two lipids found in the Covid-19 Pfizer vaccine (and also Onpattro).]
1. Onpattro Requires Premedication due to LNP Toxicity: Onpattro is a drug that requires pre-treatment with steroids and other treatments in order to circumvent known hypersensitivity reactions attributed to the LNP lipids [12][3] and complement activation in patients that are administered Onpattro, as follows: “Infusion-Related Reactions (IRRs) have been observed in patients treated with ONPATTRO (Patisiran). In a controlled clinical study, 19% of Onpattro-treated patients experienced IRRs, compared to 9% of placebo-treated patients.” [15] Onpattro lipids are shown to distribute to the liver and more in their clinical studies and animal models. The peer-reviewed medical literature, FDA labels, EMA assessments, and case studies are included below and in the references.[3][15][24][28][47][51]
2. Each person in the clinical trials for Onpattro were premedicated to complement activated adverse reactions, also called IRs, which are attributed to the LNPs in the formulation. [3] [Please note that the Onpattro patients’ dependence on Onpattro cancer drug is evident, and with Onpattro, each patient is assessed, monitored, and premedicated in attempts to avert the LNP adverse events during their treatment. They do not have a “one size fits all” treatment. Their care with these LNP drugs is individualized, monitored and they are premedicated to avoid the lipid reactions or IRs seen in section Y. Table 1. [99]]
3. Other “Unknown and Uncertainties” in Tests and Trials Require Onpattro Labeling Cautions: "The elimination in humans of the two new lipids DLin-MC3-DMA and PEG2000-C-DMG is largely unknown. As a consequence of the uncertainty of the elimination pathways and narrow exposure margins to nonclinical adverse findings, caution when used in special populations is warranted. Patisiran-LNP should not be used in patients with moderate or severe renal and/or hepatic impairment unless the anticipated clinical benefits outweigh the potential risks. This is appropriately reflected in SmPC section 4.2.[in the EMA assessment].”[3]
4. Of Note: FDA Guidelines on Labeling and Warnings in Similar Drugs: Of significance, the following section discusses FDA guidelines that recommend that adverse events in similar drugs should be included in the Adverse Events and Warnings sections of product labeling. [31][More on the labeling and warnings and other pertinent FDA guidelines are found below in the next section and more info can be seen in sections, [DD, AA, EE.7, 10 and 12, and N.2].
Next sections coming soon:
H: The Importance of Warnings, Testing, Administration Instructions, and Labeling for Drugs:
I: Nano lipids and Nanomedicine were a Narrow Field of Medicine before the COVID-19 mRNA Vaccines –for a reason--:
J: Lipid Nano – The Little Known and Unknown Science-- and the Need to Classify and Clarify Adverse Events and Reaction Rates in Nano Drugs:
K. Duty to Warn, obscured frequency of reactions statements --in non-pre-treated individuals administered PEGylated lipids, lipid nanomedicines, and nanomedicines-- and missing warnings for countermeasures/pre-treatment premedication in similar lipids for Covid-19 mRNA vaccine labeling:
L. Of importance, for percentages and frequency of reactions reported in the literature and on the FDA and manufacturer warnings for adverse reactions, to the “similar” lipid drugs:
Sneak Peek… “The elephant in the PEG room is the widespread use of SARS-CoV-2 RNA vaccines. Important questions remain to be answered, including how many people receiving BNT162b or mRNA-1273 develop antibodies against PEG, how long induced anti-PEG antibodies remain in the circulation, and whether memory B cell responses are generated. It is critical that physicians are made aware that the safety and efficacy of previously safe PEGylated medicines may change, especially if booster vaccinations of SARS-CoV-2 RNA vaccines are necessary, which seems increasingly likely as more SARS-CoV-2 variants emerge…At a minimum, more testing for anti-PEG antibodies before administration of PEGylated drugs may be warranted. Widespread use of RNA vaccines may accelerate development of PEG alternatives...” [82]
*This Executive Summary is modified for SubStack and published in a series (The LNP Files); the next sections, H through L, will be published later in the week.
*The references and citations will be posted on the last page of the series.
Please credit my work and link to this source if you repost any part of my work. Thank You
Heather Hudson 2023
About the author: Many may know me from my SubStack, media appearances, or testimony. 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 many times 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.
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.
Mrs. Hudson,
Your son is in our prayers.
In section E 7 was this statement: "The Pfizer Covid-19 mRNA-LNP vaccine did not stay in the muscle." As a retired Health Care Provider and Lawyer, the fact that Pfizer would state that the vaccine would stay in the muscle is one of the most ridiculous comments i have ever heard. It has been known, as a fact, for at least 100 years that any injection of any drug given in a muscle, that within 20 minutes the drug/vaccine would be picked up in either the lymph circulation or the vascular (blood vessel) circulation and be distributed through the body.
In F 6 is this statement: "These words in Pfizer’s internal White Paper bring about two questions, 1.) If these autoimmune reactions are “well known” to vaccines, why were the consumers not warned?..."
The retired Lawyer part of me has this response to this statement: "Consumers weren't warned, probably because Pfizer thought they could hide behind the liability shield of the PREP Act." Here is the problem with that; A valid argument could be made that failure to tell patients/victims of the "well known" autoimmune reactions is fraud! And fraud undoes any liability shield the PREP Act proports to give. Now, please understand that Pfizer has "deep pockets" and would hire a bevy of Lawyers to argue that they have absolute immunity, even from fraud, under the PREP Act. It could take a pro-tracted court battle to win, maybe even to the US Supreme Court. But it is time that Pfizer and Moderna reap their just rewards which are not Billions of $, but rather destruction of both companies, for ever!
Even the CEO of Moderna warned about the dangers of repeated exposure to LNPs in this 2016 article promoting the mRNA technology:
> https://www.statnews.com/2016/09/13/moderna-therapeutics-biotech-mrna/
-- Lipid nanoparticles "can lead to dangerous side effects, especially if a patient has to take repeated doses over months or years".
Thank you for bringing this important history to light.