Part 2 of 10- The alarming LNP history you haven't been shown- lipid and LNP developer's studies dating back 20 years: Executive Summary sent to lawmakers & investigators.

History of lipid adverse events, autoimmune case reports, eye-opening LNP developer's studies, and their data on "similar lipids" that they likely wish you would never see. These are the LNP Files...

[Please credit my work and link to this source if you repost any portion of my work. Thank You.]

This post includes the Table of Contents and sections A and B (twelve pages)of the LNP Files.

Sections D through G (also twelve pages) will be posted within the week.

Table of Contents (modified for LNP files release on SubStack):

A. Introduction and Overview of Complement Immune Responses, PEG, PEGylated lipids, and Autoimmune Reactions in Nanomedicines, Liposomes, and LNPs Pre-Pandemic.

B. Brief overview of the key mechanisms/findings and safety concerns regarding complement activation and the similarity of the Covid-19 mRNA-LNP vaccine’s lipids in relation to past lipid drugs – introduction to relevant FDA and FDA EUA reporting guidelines are introduced.

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.

D. Pre-Pandemic Biodistribution Studies Provide Information –But Covid-19 mRNA Vaccine Consumers Never Saw It.

E. The “Biomolecular Corona” LNP study was published four months before the Pfizer FDA EUA Covid-19 vaccine approvals and months before the pre-clinical animal studies approvals; “additional key study.”

F. Covid-19 vaccine adverse reactions are linked to documented autoimmune disease. Case studies and more.

G: More LNP 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.

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.

M.  Before the COVID-19 vaccines are administered to the Public: Were the COVID-19 vaccine consumers or the FDA warned of this “common” rate of CARPA (and complement-activated) reactions? If not, why not? Were they warned after these vaccines were administered?

N. After The mRNA Vaccines Were Approved and “Anaphylaxis” Adverse Reactions Were Seen, What Did The Pfizer LNP Experts Say? What Can be Found in the Animal and Medical Studies?

O. Animal studies - Pfizer Covid-19 mRNA-LNP vaccine and “similar lipid” mRNA-LNP Pfizer scientists LNP development co-authored studies.

P. Pfizer pre-clinical animal studies did not reveal the adverse events seen after the vaccine was approved. What did they show? Why did Pfizer say there are “no good animal models” to show Myocarditis? What else don’t they show?

Q. After learning about the pre-clinical studies and learning of the adverse events seen after the COVID-19 mRNA-LNP vaccines were approved, these factors and questions remain and should be considered.

R. Despite the “Low dose” and “intramuscular injection” “negligible risk” – adverse events persist- but other scientists warned of many LNP adverse events pre-pandemic.

S. Biodistribution, LNP Circulation, Circulation Time, and Complement Activation.

T. Covid-19 mRNA-LNP Vaccine products activate systemic and tissue immune response.

U. Biodistribution Pharmacokinetics Toxicology and the ABC Phenomenon.

V. Toxicity.

W. Complement and coagulation dysregulation in CARPA is said in medical studies to take place with repeated exposure/circulation of the LNPs in circulating plasma.

X. For Reference and Reminder: Complement System and Autoimmune Disease.

Y. Pfizer and Acuitas Therapeutics documents and findings on LNPs and Reactions pre and post-pandemic.

Z.  FDA “Warnings and Precautions” for adverse reactions in related drugs and the potential “cost” of the unlisted reactions.

AA. Pfizer did not include information on the related lipid drugs and adverse reactions in documents that were meant to be seen by the consumer, but they listed this information in their internal documents- Relevance in FDA EUA and WHO guidelines.

BB. How do Nano Medicine CARPA reactions seen in Related Drugs (reproducible in intravenous animal model studies) relate to FDA items 4 and 7?

CC. How Are Related Drugs With Similar Reactions Labeled?

DD. FDA EUA warnings and guidelines, and what happens when they are ignored?

EE. What about the people who suffered after their COVID-19 mRNA vaccines?

FF. What happens when the medical facts are unreported?

References are found on the last page/article in this series of Ten Articles.

Executive Summary on Sars-CoV-2 mRNA Vaccine (injectable therapies) Lipid Nanoparticles (LNPs) and Known Pre-pandemic Lipid and Liposomal CARPA (Complement Activated Reaction PSEUDO ALLERGY) and mRNA Covid-19 Vaccine Adverse Events, Myocarditis, and Autoimmunity:

Heather Hudson May 2023

Introduction: In a 2023 released 2022 Pfizer internal “White Paper” document obtained by Project Veritas, scientists elucidate the “most likely” mechanism of post-vaccine myocarditis and pericarditis seen in their Covid-19 vaccine. The Pfizer scientist concluded that the lipid nanoparticles, although designed to reduce these effects, may, indeed, be the cause of autoimmune reactions and pro-inflammatory processes that could, in turn, result in the development of myocarditis and potentially cardiac death, as shown below. [1][2]

The March 2023 Epoch Times article entitled “Pfizer Identified ‘Most Likely’ Mechanism for Heart Inflammation After COVID-19 Vaccination’” states, “In the paper, Pfizer scientists said the “most likely” mechanism was immune-mediated. The lipid nanoparticles, they said, may activate immune responses. The nanoparticles could also lead to the development of autoantibodies, or antibodies that attack a person’s immune system, they said, pointing to the case of a 52-year-old man who developed myocarditis that may have involved the generation of autoantibodies.” [1] [*Note autoantibodies attack healthy body tissue by mistake.]

Of significance, in looking further at the White Paper findings, Pfizer shows that the lipids used in the drug Onpattro LNPs are similar to the Pfizer lipids used in the Covid-19 mRNA vaccines LNP shell. Pfizer stated, “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]

Below, we will look at Onpattro, as each Onpattro patient is premedicated to prevent adverse reactions to the lipids that require assessment and premedication with steroids and other drugs to prevent adverse reactions (shown in the Onpattro studies) to be brought about by the lipids in the LNP. [3][89]

Utilizing the below referenced medical articles and studies, this paper discusses the Covid-19 mRNA vaccines’ relationship to pre-pandemic lipid nanoparticle (LNP) drugs, including reports, pre-clinical and clinical findings in drugs, and studies with similar lipids and lipid delivery mechanisms, the lipid’s role in complement activation and associated immune responses, the known potential for (and examples of) Covid-19 mRNA-LNP linked autoimmune disease, similar liposomal, PEGylated lipid and nanomedicine drug reactions, industry knowledge, the role of biodistribution and pre-clinical studies, FDA guidelines and more, as follows:

A. Introduction and Overview of Complement Immune Responses, PEG, PEGylated lipids, and Autoimmune Reactions in Nanomedicines, Liposomes, and LNPs Pre-Pandemic: Looking at studies written about lipid nanoparticles and their reactions, it seems this previously little known field of nanotechnology already had answers about nanoparticles, complement activation, the inflammatory process, autoimmune and cardiac involvement pre-pandemic.

1. Lipid nanoparticles are also known as LNPs that make up LNP shells (or the platform) in Covid-19 mRNA vaccines: These lipids were used in different formulations called liposomes. Nano lipids often contain a stabilizer called PEG (polyethylene glycol) known as PEGylated lipids used in LNP drugs including the Covid-19 mRNA-LNP vaccines. PEGylated lipids are associated with complement activation/reactions in Onpattro, Doxil, and other lipid drugs [65], discussed in this 2022 study as follows, “... the present study focused on the HSRs to Comirnaty, as it consists of PEGylated LNPs that resemble PEGylated liposomes, and “lessons” learned from nanomedicine research suggest that such nanoparticles (NPs) injected into the blood can cause so-called “infusion reactions” whose symptoms are very similar, or the same as those reported for the HSRs to LNP-mRNA vaccines ...”[28] Studies show LNP HSR (hypersensitivity reaction), called pseudo allergy  or CARPA, can be immediate or delayed, mild or severe (anaphylaxis like reactions called pseudoanaphylaxis, or anaphylactoid). [4][42] Nanoparticle reactions lack uniformity in name and are unpredictable, discussed herein.

2. History and rarity of LNP knowledge pre-pandemic: Part of the history of LNPs began when Professor Janos Szebeni learned to make liposomes in a lab in Hungary along with the (now) senior VP of BioNTech, Katalin Karikó. He also worked for the US military in this field and has written medical articles on this technology, which was a little-known field until the Covid-19 mRNA vaccines were introduced. In 2014, Szebeni stated, “Complement Activation-Related Pseudoallergy” (CARPA) is a frequent side effect of intravenous therapies with nanoparticle-containing drugs and biologicals that are recognized by the immune system as foreign. It is an acute infusion reaction dominated by cutaneous and hemodynamic changes, most significantly cardiopulmonary distress involving major pulmonary hypertension, systemic hypotension, and arrhythmias. Because CARPA is unpredictable by conventional allergy tests and it may be life-threatening, it can represent a major barrier to the safe therapeutic application of many modern medicines, including liposomal drugs and monoclonal antibodies.” “The frequency of CARPA in the 5% - 45% range is much higher than classical anaphylactic reactions to drugs (for example, penicillin allergy occurs in <2%)...” [4]

3. Onpattro Premedication Required Due To LNPs: Onpattro is a 2018 FDA-approved LNP delivery drug that Pfizer listed as a “relevant RNA therapy” and also informed its scientists in their internal “White paper” that the lipids are similar to the Pfizer Covid-19 vaccine lipids. [1][2]  Onpattro is also known as Patisiran, and according to the Patisiran /Onpattro FDA and EMA data, Onpattro is a drug that requires pre-treatment with steroids and other treatments as seen here, “In 2018, Patisiran became the first approved siRNA drug and the first approved therapy delivered via LNPs. But the drug requires an 80 min infusion every 3 weeks and pretreatment with multiple anti-inflammatory drugs to minimize reactions to the nanoparticle.” [15][3][24][51] Also, as seen here, on the FDA Application Data Sheet for Onpattro, which states, “Infusion-related reactions (IRRs) are a known concern with LNP drugs and occurred in 19% (of patisiran-treated patients in Study 004), compared to 9% of placebo-treated patients.” [89][3]

4. An example of a premedicated vs. non-premedicated rate of reaction in LNP reactions: Doxil also uses a similar PEG 2000 lipid and is often mentioned in studies. This 2019 “PEGylated Liposomes” article states, “The use of Doxil has been implicated in acute infusion reactions in up to 45% of the cancer patients who receive the drug without premedication with steroids and antihistamines, while 4–7.1% in pre-medicated patients ...[7] The importance of designating whether reaction rates include premedicated consumers (or not) is critical to understanding the frequency of these lipid reactions.

5. CARPA reactions are dysregulated or unwanted Complement System Activated Reactions: According to the Cleveland Clinic, the complement system is a necessary part of your body’s immune system that cleans up your body’s damaged cells, destroys microscopic organisms, and is responsible for immune regulation in the body. [68] However, as found in medical studies, complement dysregulation and immune-mediated dysfunction can take place when LNPs circulate in blood plasma. According to these studies, size, shape, and curvature of the nanoparticles and factors such as biodistribution can affect this circulation and immune stimulation. [3][27][28][29][30][72]

6. CARPA complement pseudoallergy has been historically miscategorized: In 2018, Szebeni co-authored this article on the role of complement activation in HSRs, which explains, “HSRs have been traditionally categorized in four groups, from I to IV, according to Coombs and Gell. This concept defined Type I reactions as IgE-mediated acute reactions, while the rest of the categories included subacute or chronic immune changes triggered or mediated by IgG, immune complexes, or lymphocytes... However, it has increasingly been recognized that a substantial portion of acute allergic reactions, whose symptoms fit in Coombs and Gell’s Type I category, are actually not initiated or mediated by pre-existing IgE antibodies. These reactions are known to be “pseudoallergic” or “anaphylactoid.” There are estimates that 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]

7.  Relatively unknown reactions outside of the nanomedicine field: In this 2020 Science magazine article, written just after the Covid-19 mRNA vaccines saw at least eight people develop severe allergy-like reactions, it states, “Szebeni says the mechanism behind PEG-conjugated anaphylaxis is relatively unknown because it does not involve immunoglobulin E (IgE), the antibody type that causes classical allergic reactions. (That's why he prefers to call them "anaphylactoid" reactions.) Instead, PEG triggers two other classes of antibodies, immunoglobulin M (IgM) and immunoglobulin G (IgG), involved in a branch of the body's innate immunity called the complement system…”[6]

[Just like Galileo attempted to explain the solar system and was censored and ridiculed for his findings, the history of lipid adverse events has struggled to overcome the fact that lipid reactions include far more reactions than allergies. The lipid adverse events can be deadly, life-threatening, and more. They can include complement activation, likely ASIA-type reactions (see the case studies in sections F and more), and other immune-mediated mechanisms that are severe and serious in nature (as shown in the medical literature presented herein). The makers of these lipids (in current lipid-delivered therapies, and coming lipid-delivered therapies (flu shots and more)) have historically not had to deal with the public knowing the full details on lipid and LNP adverse events, as this was a highly specified area of medicine before the Pandemic and LNP delivery mRNA Covid-19 vaccines .]

8. An Introduction to PEG and PEGylated Lipids and their Role in CARPA: Previous to the Covid-19 mRNA vaccines, in the past iterations of these infused lipid drugs (which had been used in a relatively small field of mainly cancer drugs and also in some imaging and now the present Covid-19 vaccines (as an injection)), the lipids (especially PEGylated lipids) and their ability to cause inflammation, “anaphylaxis,” heart inflammation, and more (including links to autoimmune or autoantibody development) are pointed out in the medical literature utilized in these fields of medicine. PEGylated lipids contain PEG (polyethylene glycol), which acts as a stabilizer when used in lipid nanoparticles.

This 2021 article titled, “Allergenic components of the mRNA-1273 vaccine for COVID-19: Possible involvement of polyethylene glycol and IgG-mediated complement activation” explains PEG and CARPA reactions further, as seen here, “Lipid nanoparticles are similar to liposomes, … CARPA is partly attributed to the binding of preexisting anti-PEG IgM to the liposomes with subsequent complement activation… Clinical symptoms of this non-IgE-mediated hypersensitivity have been described as hypo- and hypertension, airway obstruction with dyspnea, and other anaphylaxis symptoms shortly after the intravenous administration of liposome-containing drugs… Independent of PEGylation, liposomes have the potential to activate complement, non-specifically depending on their different surface structures and charge… Anaphylatoxins are liberated during complement activation…” [48].

Next, we learn from the highly specified literature that individuals can have an allergy to PEG, which is a traditional allergy that can be tested and treated in the manner that allergies are treated. But what is most relevant, and troubling is that we are also told in these findings that one does not have to be allergic to PEG to have a life-threatening reaction to PEGylated lipids, as is found in CARPA. An allergy test for PEG will not alert an individual to the possibility of having a CARPA reaction that can be “sometimes deadly,”[14] nearly fatal, or a lesser reaction --potentially life-altering, as seen below.

a. More can be seen in this 2013 “Cardiopulmonary and hemodynamic changes in complement activation-related pseudoallergy” article, where it states, “The most important distinguishing feature of CARPA seems to be the lack of pre-sensitization and reinforcement, that is already the first exposure to a given noxious event or drug elicits maximal and in some cases fatal cardiovascular reaction. Upon repeated exposure, the response decreases, frequent tachyphylaxis develops ... “[94].

b. This 2022 article, “Understanding the Role and Impact of Poly (Ethylene Glycol) (PEG) on Nanoparticle Formulation: Implications for COVID-19 Vaccines,” states, “Blood analysis collected soon after the administration of Doxil showed fragments from the complement cascade and the complement activation was proposed as a mechanism behind these hypersensitivity reactions (Chanan-Khan et al., 2003; Szebeni et al., 2011). These non-IgE-mediated hypersensitivity reactions are known as complement activation-related pseudoallergy (CARPA), with symptoms very similar to the type I hypersensitivity reaction, though they occur upon first contact without prior exposure and lack a specific allergen, which is why it is called “pseudoallergy”…” [5].

c. Doxil is a PEGylated liposomal drug that uses PEG 2000 lipid or PEGylated lipid (as is also used in the Pfizer Covid-19 mRNA-LNP vaccines), and it is currently in use. What is significant is that we learn about the pre-treatment premedication measures taken to prevent CARPA pseudo allergy reactions for the administration of this drug, found in the Doxil literature- warnings and FDA data (provided below). [14] [Doxil administration is closely monitored in the cancer patients who are given this drug.]

d. CARPA findings in the LNP and liposomal drugs are significant as we see in the references that CARPA and the Complement Reaction have been shown in immune-mediated activation and toxicity [6][7][8], which is relevant given the findings in the Pfizer documents that show the myocarditis ““most likely” mechanism was immune-mediated. The lipid nanoparticles, they said, may activate immune responses. The nanoparticles could also lead to the development of autoantibodies, or antibodies that attack a person’s immune system.” They conclude, “In reviewing the potential known causes of myocarditis or pericarditis in general, an immune-mediated mechanism seems most likely...” [1][2]. [*Note autoantibodies attack healthy body tissue by mistake.]

e. Knowing the above information was not presented to Covid-19 mRNA-LNP vaccine consumers, this Executive Summary looks further into the FDA EUA guidelines and the materials, studies, and information given to the FDA by Pfizer, including the pre-clinical or animal studies and more.

9. Nano Lipid circulation time and biodistribution - its role and importance in Complement Activation: This February 2020 article called “Immunogenicity of Polyethylene Glycol Based Nanomedicines” describes PEG, circulation time, and more, “PEGylation technique is currently considered the gold standard approach to provide a long and safe circulation of drugs. Although this is the accepted dogma, various clinical reports and animal studies show the occurrence of immunogenic responses against polyethylene glycol (PEG) after systemic injection. These side effects, associated with complement activation and/or anti-PEG antibody production, result in hypersensitivity reactions and lack of therapeutic efficacy of the drug during clinical protocols.” [65]

10. Cardiovascular Symptoms, Complement Activation, and “Anaphylactic” Reactions: In this 2019 NIH article called “PEGylated Liposomes: immunological responses,” it states, “Hugli … studied complement activation and described the structures and roles of anaphylotoxins, primarily C3a and C5a, in complement-mediated adverse drug reactions. In animal studies, interestingly, they discovered that C3a and C5a are effective regulators in autonomic and cardiovascular organ function. Moreover, they suggested that over-expression of C3a and C5a in complement activation explains the cardiovascular symptoms and other symptoms of anaphylactic reactions.... Szebeni reported that CARPA is an independent class of type I reactions, exhibiting receptor-mediated mast cell activation ... “ The study continues to say, “Several drugs and agents cause CARPA, including radiocontrast media, liposomal drugs…” [71]

11.  Pre-clinical animal studies such as biodistribution studies are a key factor for FDA Covid-19 mRNA vaccine safety studies: According to the Encyclopedia of Cancer, “Drug Biodistribution is the study of the fate of a drug in the body in terms of localization in the tissues.” The circulation or biodistribution studies of the lipids/drugs are part of the Pfizer pre-clinical animal studies. The LNP studies (kinetics, pharmacokinetics, and safety studies) (and what they reveal) are discussed throughout this Executive Summary due to their key role in understanding the safety of the Pfizer Covid-19 mRNA vaccines.

12. CARPA is one example of many potential Complement Activated Reactions: CARPA reactions linked to the LNPs can be “sometimes fatal,” according to the Doxil FDA patient sheet. [14] However, bleeding and blood clotting disorders are also included, as the medical studies and animal studies surrounding LNPs show that unwanted or dysregulated immune cascades, coagulation parameters, complement activation, or “immune reactions” can take place as seen in the animal studies, case studies and medical references in this Executive Summary. [2][14][22][47][90] Of note: Empty LNPs are associated with complement activation and even low doses of LNP are associated with other unwanted reactions such as “changes in the coagulation parameters at all doses” as shown here: [47].

13. Complement dysregulation is also discussed in Autoimmune (autoantibodies that attack the body’s own cells) and Cancer diseases: [70] The below 2019 Frontiers in Immunology study states, “there is a lurking “dark side” that can lead complement astray, fueling a self-perpetuating vicious cycle of inflammation that results in persistent immune activation and irreversible tissue injury in both acute and chronic pathologies ... Indeed, complement dysregulation or excessive activation have been recognized as key pathogenic drivers in a wide spectrum of inflammatory, immune-mediated, and age-related neurodegenerative diseases...  Besides cancer, complement activation has long been implicated in the pathogenesis of autoimmune diseases, but clinical translation in this area has remained a conundrum.”[8] Also, this Frontiers in Science 2019 article states, “In 2008, making a paradigm shift in tumor immunology, we demonstrated that complement activation, followed by C5a signaling, has a tumor-promoting role in cancer.” “Insights into how complement switches from tumor suppressing to tumor promoting activities at the onset of disease, as well as how to manage this dichotomy should be important research areas in order to establish the best therapeutic strategies.” [92]

14. Complement and Autoimmunity: As seen here, in this 2019 article titled, “Complement, infection, and autoimmunity,” it states, “Complement system dysfunction in terms of upregulation, downregulation, or dysregulation can create an imbalance of both host defense and inflammatory response leading to autoimmunity.” [32]

15. Pfizer proposes mechanisms of lipid and LNP immune dysregulation: Pfizer’s 2022 internal White Paper document obtained by Project Veritas in 2023 also states, “Lipid components in the LNP may also activate host immune responses following systemic or local administration (Hou et al, 2021). For example, PEG-lipids may stimulate the complement system. Cationic and ionizable lipids have also been reported to stimulate the secretion of pro-inflammatory cytokines and reactive oxygen species. Although the immune responses to these lipids has not yet been fully understood, complement system and Toll-like receptors may participate in innate immune activation (Hou et al, 2021). Also, minor differences in biophysical characteristics of LNP (eg. particle size, homogeneity, shape, and liposome lamellarity) may also have an effect.” This Pfizer internal document also described the case of myocarditis linked to the Pfizer mRNA vaccines that “may have been involved [in] the generation of autoantibodies.” [2]

16. mRNA Vaccination Induced Autoimmunity:  Mayo Clinic physicians in their 2022 “SARS-CoV-2 mRNA Vaccination-induced Autoimmune Polyarthritis-like Rheumatoid Arthritis” article state, “…cases of mRNA vaccination-induced autoimmunity do exist,” (as well as numerous case studies are provided below in which the mRNA-LNP  Covid-19 mRNA vaccines are linked to near-fatal, life-altering, and milder autoimmune reactions), this Executive Summary document details these factors within the study of the LNP and the affected systems. [91][See the table of adverse events for the similar/relevant Onpattro drug in section Y; see “Connective Tissue disorders.”]

Section A recap:  The above section briefly details the history of liposomes up to the newer Covid-19 mRNA vaccine LNPs  (NPs). Medical journal articles quoted material, findings, and references surrounding the liposomal and LNP adverse events, including complement-activated adverse events, cardiopulmonary distress, potential myocarditis, and mRNA vaccine-induced autoimmunity, are provided. Complement activation in coagulation and cancers are also briefly introduced along with the introduction to the studies that highlight the mis- categorization and little-known nature of these adverse events outside of the lipid science field.

B. Brief overview of the key mechanisms/findings and safety concerns regarding complement activation and the similarity of the Covid-19 mRNA-LNP vaccine’s lipids in relation to past lipid drugs – introduction to relevant FDA and FDA EUA reporting guidelines are introduced:

1.  The interaction of the LNPs and lipids circulating in the body are key factors in complement activation: As seen in this Frontiers in Science Article, which states, “…undesired interactions with circulating complement proteins can affect the pharmacokinetics and tolerability of nanoparticle-mediated drugs.” [29] Further, a 2018 animal study of mRNA and LNP therapeutic drugs, co-authored by a Moderna VP, shows that the empty LNP saw complement activation without a carrier drug.[47]

2. Complement and Time-Delayed Reactions: This 2020 MDPI article states, “Complement has a role to play in both the immediate and time-delayed reactions of type I hypersensitivity. Via the production of the anaphylatoxins C3a and C5a, complement is involved in the recruitment of inflammatory cells…”[42] The 2020 EMA Pfizer report shows the lipid remains in the human body for four to five months (Section O.12). [67] Studies also show that LNP circulation time plays a role in complement activation.

3. Circulation time and complement activation: In this 2016 “Nanodrug Delivery” article, it states, “nano-sized drugs have long circulation times associated with higher toxicity”[27]. Long circulation times provide the LNPs with more contact with complement proteins which, as seen here, according to the Cleveland Clinic article, we are told that “If your complement proteins are working too hard and activating too frequently, you may be at risk for several autoimmune or inflammatory conditions.” [30]

4. Elusive Complement Reactions and C Reactions: In 2014, Szebeni et al. reported, “Severe reactions can cause major anxieties, disruptions, and exclusion of the patient from receiving a potentially useful life-saving treatment. These reactions can also be fatal in a small percentage of hypersensitive individuals, mainly those with a history of severe allergy and/or heart disease... Complement activation during cardiopulmonary bypass with the involvement of C3a and C5a anaphylatoxins was reported decades ago.., which was later confirmed, and the involvement of C-reactive protein in association with postoperative arrhythmia was also described...”[4]

5. FDA Labeling, Warnings, and Similar Drugs: The 2007 FDA guidelines for drug labeling recommend that adverse drug reactions and adverse events in similar drugs should be included on the drug labels “whether the adverse event is known to be caused by related drugs” and also “usage is associated with a clinically significant risk or hazard” (discussed and referenced in detail in further sections below). Why didn’t the vaccine manufacturers include the information on the similar lipid, liposomal, and LNP shell adverse reactions and rates of reactions in the FDA EUA? Instead, safety and warning information was provided only for traditional vaccines that do not have lipid shells and are not RNA gene therapies. Please see sections [DD, AA, EE.7, 10, and 12, and N.2] for EUA and WHO guidelines.

6.  Quick introduction- Onpattro LNPs warnings and information on complement, coagulation, and more: Pfizer showed that the Onpattro lipids are similar to Pfizer Covid-19 vaccine lipids in their internal “White Paper” above and in medical literature presented within this summary; however, the adverse reactions for the similar Onpattro lipids were not included in Pfizer’s FDA EUA information to consumers and providers. Aside from the IRRS Infusion/lipid reaction, the 2018 EMA provided further Onpattro information and warnings for LNP-related issues as follows [3][15][89][Also see the Onpattro adverse reactions table in section Y] :

• “Since the non-clinical and clinical experience so far with therapeutic oligonucleotides (mainly of the ASO (DNA-based) class) has shown that these may lead to class and platform related adverse effects which include immune stimulation…” [Note: Platform = LNP and DNA based drugs are delivered via LNPs or nano drugs.] [3][15][89]

• “Infusion-related reactions were more common in the patisiran (18.9%) than in the placebo (9.1%) group. All IRRs were mild to moderate and resolved… [3][15][89] (However, all participants of the trial and all who are prescribed Patisiran/Onpattro to date are pre-medicated in attempts to alleviate the “infusion-related reactions that are associated with the lipids according to their findings in the patient fact sheets (see last bullet point).)

• “Complement factors and cytokines/CRP Activations of the alternative complement pathway and immune stimulation have been described for other therapeutic oligonucleotides (mainly of the ASO (DNA-based) class)…” [3][15][89]

• “Development of treatment-emergent ADA to PEG2000- C –DMG was rare and occurred in both patisiran- (3.4%) and placebo-treated patients (1.30%) in study 004. There was no correlation between ADA and IRRs, anaphylactic reactions, or hypersensitivity events. PEG2000-C-DMG is exposed on the surface of patisiran-LNP to the immune system. Anti-PEG-ADA have also been described in subjects treated with PEGylated protein drugs.” [Note: ADA= anti-drug antibody.] [3][15][89]

• “In general, the non-clinical and clinical experience so far with therapeutic oligonucleotides (mainly of the ASO (DNA-based) class) has shown that these may lead to adverse effects related to immune stimulation, activation of C’ alternative pathway and inhibition of the coagulation cascade, as well as tissue accumulation in the liver, kidneys, spleen and lymph nodes.” [3][15][89]

• “Patisiran is encapsulated in a lipid nanoparticle (LPN) in the circulation. Non-clinical studies have shown that the toxicity primarily is related to the liposomal formulation and not to the siRNA itself.” [Note: LNP means lipid nanoparticle; LPN was written in the Onpattro assessment]. [3][15][89]

7. CARPA is different than an allergy: 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 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. [29][28][2][3]This means that the presence of the nanoparticles alone can bring about reactions that, sadly, can be fatal or nearly fatal, and this is why pre-pandemic, many of these LNP and PEGylated nano lipid drugs have been pre-treated and pre-medicated or assessed and administered in infusion centers with teams ready to assist and assess during drug administration. This is true for the similar lipid drug Onpattro, but consumers were not warned of complement dysregulation and CARPA in the FDA EUA for the mRNA-LNP vaccines. [3] This information should be known by the consumer as well as included on the labeling to prevent misdiagnosis and more.

8. Potential Delays, mislabeling, and misdiagnosis without proper consumer and provider education and warnings: Immediately after the clinical trials, when the general population began receiving doses of the C-19 mRNA-LNP vaccines, hypersensitivity reactions were reported worldwide, and cases in Australia, Canada, England, and the US made the news. Still, many vaccine-induced complement reactions may not have been attributed to the Covid-19 mRNA vaccines, as we have learned in the literature that the symptoms can be delayed and mislabeled/misdiagnosed due to the little-known complement reactions in LNP drugs. [4][18][28][42]. Sadly, CARPA, dysregulated, or unwanted complement reactions (such as potential autoimmune reactions/disorders) were not named in the warnings of the Pfizer or Moderna FDA EUA and, therefore, could not have been anticipated by consumers or providers, even though LNPs and their safety studies include a significant history of these adverse events/reactions (especially CARPA events) in the small settings in which they were used pre-pandemic. [4][28][42][66][67]

9. Complement Activated Reactions are not Limited to Anaphylaxis and Hypersensitivity Reactions --Equally Harmful Gradual or Non-Immediate Reactions Are Known: 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. Further details, including autoimmune COVID-19 mRNA vaccine-linked case studies, in which autoimmune-mediated reactions can have sudden and catastrophic events, are provided in section “F.” But before discussing that section, important information on the pre-clinical/animal studies that are meant to show these possible safety issues in these (drugs/vaccines/formulations) before they are given to humans is discussed below in section C.  

*This Executive Summary is modified for SubStack and published in a series (The LNP Files); the next sections, C through G, will be published later in the week. The references and citations will be posted on the last page of the series (see the above Table of Contents).

[Please credit my work and link to this source if you repost any portion of my work. Thank You.]

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