James Odell, OMD, ND, L.Ac.
Editorial - The material published in this editorial is intended to foster scholarly inquiry and a rich discussion of the controversial topic of bioethics and health policy. The views expressed in this article are solely the authors and do not represent the policy or position of the Bioregulatory Medicine Institute (BRMI), nor any of its Board Advisors or contributors. The views expressed are not intended to malign any religious or ethnic group, organization, company, individual, or any other. Every effort has been made to attribute the sources of this article to the rightful authors listed in references.
With the recent licensing and roll out of COVID-19 vaccines in the U.K., Canada, the U.S. (Pfizer/ BioNTech and Moderna), and Russia (Sputnik) there are several serious safety concerns that have not been addressed or even mentioned in the medical media. In short, it is beyond reckless and totally unnecessary to administer these experimental vaccines to millions of people when there is only limited short term safety data. Absolutely no long-term safety studies have been done to ensure that any of these vaccines do not cause cancer, seizures, heart disease, allergies, and autoimmune diseases, as seen with other vaccines and observed in earlier coronavirus vaccine animal studies. Because animal studies were bypassed for these vaccines due to ‘fast-tracking’, millions of humans are now the primary test animal. Additionally, these vaccines were developed using a completely new mRNA technology that has never been licensed for human use. In essence, we have absolutely no knowledge of what to expect from these new mRNA vaccines. Since viruses mutate frequently, the chance of any vaccine working for more than a year is unlikely. That is why the influenza (flu) vaccine changes every year. This editorial comprehensively discloses current COVID-19 vaccine development, administration, and safety concerns in detail.
Ribonucleic acid (RNA) is a nucleic acid present in all living cells. Its principal role is to act as a messenger carrying instructions from DNA for controlling the synthesis of proteins. Although in some viruses’ RNA rather than DNA carries the genetic information. In each cell of a living organism, DNA is the molecule that contains the genetic information of the organism. It is composed of a series of four building blocks, whose sequence gives the instructions to fabricate proteins. This process requires a transient intermediary called messenger RNA that carries the genetic information to the cell machinery responsible for protein synthesis. RNA is the only molecule known to recapitulate all biochemical functions of life: definition, control, and transmission of genetic information, creation of defined three-dimensional structures, enzymatic activities, and storage of energy.
RNA became the focus of intense research in molecular medicine at the beginning of the millennium. Messenger viral RNA (mRNA) is now developed as a vaccine and this technology poses many questions and serious health concerns that have been left unanswered by the vaccine manufacturers. Unlike previous vaccines an mRNA vaccine is a new type of vaccine that inserts fragments of viral mRNA into human cells, which are reprogrammed to produce pathogen antigens, which then if all goes well, stimulate an adaptive immune response against the targeted pathogen. That seems straightforward, but what else is in the vaccines, and is this new technology truly proven safe and effective?
History of Coronavirus Vaccine Animal Studies and
Antibody Dependent Enhancement (ADE)
Researchers have been trying to develop a coronavirus vaccine since the Severe Acute Respiratory Syndrome (SARS-1) outbreak in 2002. Thus, over a span of 18 years there have been numerous coronavirus vaccine animal studies conducted, which unfortunately demonstrated significant and serious side-effects. Either the animals were not completely protected, became severely ill with accelerated autoimmune conditions, or died.1, 2, 3, 4, 5, 6, 7
Animal side effects and deaths were primarily attributed to what is called Antibody-Dependent Enhancement (ADE). In the 1960s, immunologists discovered ADE and since then have extensively researched and identified its mechanism. Virus ADE is a biochemical mechanism in which virus-specific antibodies (usually from a vaccine) promote the entry and/or the replication of another virus into white cells such as monocytes/macrophages and granulocytic cells. This then modulates an overly strong immune response (abnormally enhances it) and induces chronic inflammation, lymphopenia, and/or a ‘cytokine storm’, one or more of which have been reported to cause severe illness and even death. Essentially, ADE is a disease dissemination cycle causing individuals with secondary infection to be more immunologically upregulated than during their first infection (or prior vaccination) by a different strain. ADE of disease is always a concern for the development of vaccines and antibody therapies because the mechanisms that underlie antibody protection against any virus has a theoretical potential to amplify the infection or trigger harmful immunopathology.8, 9, 10 ADE of the viral entry has been observed and its mechanism described for many viruses including coronaviruses.11, 12, 13 Basically, it was shown that antibodies target one serotype of viruses but only sub neutralize another, leading to ADE of the latter exposed viruses. Thus, ADA of viral entry has been a major concern and stumbling block for vaccine development and antibody-based drug therapy. For example, it has been shown that when patients are infected by one serotype of dengue virus (i.e., primary infection), they produce neutralizing antibodies targeting the same serotype of the virus. However, if they are later infected by another serotype of dengue virus (i.e., secondary infection), the preexisting antibodies cannot fully neutralize the virus. Instead, the antibodies first bind to the virus and then bind to the IgG Fc receptors on immune cells and mediate viral entry into these cells.14 A similar mechanism has been observed for HIV, Ebola, and influenza viruses. Thus, sub neutralizing antibodies (or non-neutralizing antibodies in some cases) are responsible for ADE of these viruses.15, 16, 17, 18, 19, 20
Generally, the conclusion of some of those studies was that great caution needs to be exercised when moving forward to human trials primarily because of the potential of accelerated autoimmunity reaction. Because ADE has been demonstrated in animals21, coronavirus vaccine research never progressed to human trials, at least not till the recent SARS coronavirus-2 fast-track campaign.
More technical Understanding of SARS-CoV-2 ADE Mechanisms
As a forementioned, a potential barrier to the development of safe and efficacious COVID-19 vaccines is the risk that insufficient titers of neutralizing antibodies might trigger ADE of disease. Previous research in SARS-CoV infection demonstrated ADE is mediated by the engagement of Fc receptors (FcRs) expressed on different immune cells, including monocytes, macrophages and B cells.22, 23, 24 A Fc receptor is a protein found on the surface of certain cells – including, among others, B lymphocytes, follicular dendritic cells, natural killer cells, macrophages, neutrophils, eosinophils, basophils, human platelets, and mast cells – that contribute to the protective functions of the immune system.
Akiko Iwasaki and colleagues describe this coronavirus ADE mechanism in more detail in their 2020 research published in Nature Reviews Immunology.25 They confirm that pre-existing SARS-CoV-specific antibodies may thus promote viral entry into FcR-expressing cells. This process is independent of ACE2 expression and endosomal pH and proteases, suggesting distinct cellular pathways of ACE2-mediated and FcR-mediated viral entry.
In short, previous experience with veterinary coronavirus vaccines and animal models of SARS-CoV and MERS-CoV infection has raised safety concerns about the potential for ADE and/or vaccine-associated enhanced respiratory disease. These events were associated either with macrophage-tropic coronaviruses susceptible to antibody-dependent enhancement of replication or with vaccine antigens that induced antibodies with poor neutralizing activity and Th2-biased responses.
After two decades of failed animal trials, the question is posed as to why fast-tracking coronavirus vaccine will now result in a different outcome? Given that many of these fast-track trials have bypassed animal studies, are only performed on healthy volunteers and children (not the elderly or those with pre-morbidities), and that trials are conducted without an inert double-blind placebo-controlled environment, and are not given sufficient time to observe effects on the human trials, there is a serious safety concern. Many, many virologists, and epidemiologists feel this fast-track policy is a recipe for mass disaster. Microbiologist Dr. Sucharit Bhakdi and Dr. Karina Reiss in their new book Corona, False Alarm? give clarity to many of the issues surrounding the pandemic, especially the current coronavirus vaccines.26
Traditional vs. mRNA Vaccines
Historically, the manufacturing process for creating vaccines involves many trade secrets and numerous other ingredients as adjuvants and preservatives.27, 28 ‘Traditional or classical vaccines’ may contain attenuated or inactivated viruses and bacteria or proteins, as well as adjuvants, such as aluminum, to stimulate an immune response that produces artificial immunity, as well as a host of other ingredients called “excipients”. For example, older viral vaccines for smallpox and measles vaccine contain live attenuated viruses; injectable influenza vaccines contain inactivated viruses; the recombinant hepatitis B virus vaccine is a protein subunit vaccine, while the newer human papillomavirus (HPV) virus vaccine contains virus-like particles.
To date, there are several different types of potential vaccines for COVID-19 in development, including:
Inactivated or weakened virus vaccines, which use a form of the virus that has been inactivated or weakened, but still generates an artificial immune response.
Protein-based vaccines, which use fragments of proteins or protein shells that mimic the COVID-19 virus to generate an artificial immune response.
Viral vector vaccines, which use a virus that has been genetically engineered to generate an artificial immune response.
RNA and DNA vaccines, that uses genetically engineered RNA or DNA to generate a protein that itself prompts an artificial immune response.
For the past two decades, researchers have been experimenting with new technology platforms, notably ones that introduce foreign DNA and RNA into cells of the body, to develop experimental vaccines for SARS, MERS, HIV, and other diseases but, historically none have been proven effective and safe for humans.
Thus, for a traditional vaccine, the antigen is introduced in the body to produce an immune response. However, in the case of DNA- or RNA-based vaccines, no antigen is introduced, only the RNA or DNA containing the genetic information to produce the antigen. That is, for this specific class of vaccines, the introduction of DNA and RNA provides the instructions to the body to produce the antigen itself.29
mRNA vaccines differ greatly in their design and biochemical mechanisms from traditional vaccines. Traditional vaccines stimulate an antibody response by injecting a human with antigens (proteins or peptides), or an attenuated virus, or a recombinant antigen-encoding viral vector. These ingredients are prepared and grown outside of the human body, which takes time, and even when they are injected into the bloodstream, they do not enter the human cell.30
In contrast, mRNA vaccines insert a synthetically created fragment or snip of the virus RNA sequence directly into the human cells (known as transfection). This snip of viral RNA material then activates an enzyme called reverse transcriptase which replicates that RNA snip repeatedly. This then reprograms the cells to produce their own viral antigens, which, if all goes as planned, stimulates an adaptive immune response, resulting in the production of new antibodies that bind to the antigen and activate T-cells.31, 32, 33
Simply speaking, the new mRNA vaccines inject (transfects) molecules of synthetic genetic material from non-human sources (viral sequences) into our cells. Once in the cells, the genetic material interacts with our transfer RNA (tRNA) to make a foreign protein that supposedly teaches the body to destroy the virus being coded for. These created proteins are not regulated by our own DNA and are thus completely foreign to our cells. What they are fully capable of doing is completely unknown.
Till now, messenger-RNA vaccines have never been licensed for public use. In the last two decades, there has been deep-pocket funding for the development of mRNA vaccines against infectious diseases, particularly with the currently declared pandemic and vaccine fast track campaign. Historically, their application has until recently been restricted by the instability and inefficient in vivo delivery of mRNA. New technological advancements in RNA biology, chemistry, stability, and delivery systems have now accelerated the development of fully synthetic mRNA vaccines. The consensus is that mRNA vaccines are faster and cheaper to produce than traditional vaccines and for vaccine manufacturers, more cost-effectiveness translates to greater profits. Certainly, there are unique and unknown risks to messenger RNA vaccines, including local and systemic (ADE) inflammatory responses that could lead to autoimmune conditions.
mRNA Vaccines Mechanisms
mRNA vaccines have strands of genetic material called mRNA inside a special coating. That coating protects the mRNA from enzymes in the body that would otherwise break it down. It also helps the mRNA enter the muscle cells near the vaccination site. mRNA vaccines use a different approach that takes advantage of the process that cells use to make proteins: cells use DNA as the template to make messenger RNA (mRNA) molecules, which are then translated to build proteins. An RNA vaccine consists of an mRNA strand that codes for a disease-specific antigen. Once the mRNA is in the cell, human biology takes over. Ribosomes read the code and build the protein, and the cells express the protein in the body. Thus, cells use the genetic information to produce the disease-specific antigen. This antigen is then displayed on the cell surface, where it is recognized by the immune system.34
mRNA vaccines have been studied before for influenza, Zika, rabies, and cytomegalovirus. The concept for the development of an mRNA vaccine is rather straightforward. Once the antigen of choice from the pathogen target is identified, the gene is sequenced, synthesized, and cloned into the DNA template plasmid. mRNA is then transcribed in vitro, and the vaccine is delivered to the subject. The mRNA vaccine utilizes the host cell machinery for in vivo translation of mRNA into the corresponding antigen, thereby mimicking a viral infection to elicit potent humoral and cellular immune responses. The final cellular location of the antigen is determined by the signal peptide and transmembrane domain. This can be intrinsic to the natural protein sequence or engineered to direct the protein to the desired cellular compartment.35, 36
Once the viral mRNA is injected into the body, it faces immune responses that are programmed to destroy it. Our cells have evolved elaborate defense mechanisms intended to destroy foreign, unprotected, or “naked” RNA. However, the susceptibility of mRNA to degradation can be reduced by modifying the RNA during synthesis. One modification is to add in ‘nucleoside analogs’ that resemble the normal nucleosides found within RNA (A, U, C and G,) but have minor structural changes that make the RNA more resistant to enzyme degradation by the body’s ribonucleases. (Nucleosides are the structural subunit of nucleic acids such as DNA and RNA.)
Additional structural modifications and the inclusion of regulatory sequences can also improve the stability of mRNA.37 For example,the vaccine viral mRNA is delivered in the form of a complex with lipid nanoparticles, to stabilize the mRNA, making it easier to penetrate the cell, and increases the amount of antigen produced per cell.38 Lipid nanoparticle formulations also elicit a stronger immune response compared to naked mRNA.39This is where it gets tricky and potentially dangerous because some of the lipid nanoparticles developed for these mRNA vaccines can be strongly immunologically reactive and elicit an unwanted autoimmune reaction.
PEGylated Lipid Nanoparticles
Thus, mRNA is threatened by rapid degradation by ubiquitous extracellular ribonucleases before being taken up by cells.40 The mRNA molecule is also vulnerable to destruction from temperature changes as well as our immune system. Thus, the efficacy of mRNA vaccines requires ‘complexing agents’ which protect RNA from degradation. Complexation may also enhance uptake by cells and/or improve delivery to the translation machinery in the cytoplasm. To this end, mRNA is often complexed with either lipids or polymers. These mRNA vaccines are coated with PEGylated lipid nanoparticles (polyethylene glycol). This coating hides the mRNA from our immune system which ordinarily would attack and destroy kill any foreign material injected into the body. PEGylated lipid nanoparticles have been used in several different drugs for years. Unfortunately, PEGylated lipid nanoparticles have been shown to imbalance certain immune responses and can induce allergies and even autoimmune diseases.41, 42, 43, 44, 45, 46
A 2016 study in Analytical Chemistry reported detectable and sometimes high levels of anti-PEG antibodies (including first line-of-defense IgM antibodies and later stage IgG antibodies) in approximately 72% of contemporary human samples and about 56% of historical specimens from the 1970s through the 1990s. Of the 72% with PEG IgG antibodies, 8% had anti-PEG IgG antibodies > 500ng/ml., which is considered extremely elevated.47 Extrapolated to the U.S. population of 330 million who may receive this vaccine, 16.6 million may have anti-PEG antibody levels associated with adverse effects.The researchers confessed that the results were entirely unexpected. The authors concluded that:
“…sensitive detection and precise quantitation of anti-PEG Ab levels in a clinical setting will be essential to ensuring the safe use of PEGylated drugs in all target patient populations going forward.”
Multiple previous studies regarding the prevalence of anti-PEG antibodies in the population have stated that pre-screening should be done prior to any administration of a PEG-containing medication. Screening is likely to be even more important in the case of a vaccine intended for parenteral administration to as many people as possible that contains a substance to which a majority of the population unknowingly has anti-PEG antibodies.
Production of mRNA vaccines
To further understand PEGylated lipid nanoparticles and their role in vaccine delivery, it is helpful to understand a little more about how an mRNA vaccine is manufactured. A major manufacturing advantage of mRNA vaccines is that RNA can be produced in the laboratory from a DNA template using readily available materials, again less expensively and faster than conventional vaccine production, which utilize a variety of cell types such as chicken eggs or other mammalian cells such a fetal material.48 This all comes down to economics. It is faster and cheaper to make.
Traditional vaccines normally contain a strong adjuvant (often aluminum) supplying an enhanced signal for the initiation of the adaptive immune response. However, it is thought that mRNA vaccines sort of have their own adjuvant effect by themselves, partly by virtue of being foreign nucleic acids. It has not been disclosed if any of these candidates (from any company) have an adjuvant added to them. (More information on adjuvants later in this article.)
Moreover, according to Arcturus, the company manufacturing the Pfizer/BioNTech lipid delivery system, this involves a multi-component delivery system called LUNAR® (Lipid-enabled and Unlocked Nucleomonomer Agent modified RNA). “This system has access to over 150 proprietary lipids that have been utilized for mRNA-based COVID-19 vaccines.”49 Basically, all we know is this involves proprietary PEGylated lipid nanoparticles.