Worse Than the Disease? Reviewing Some PossibleUnintended Consequences of the mRNA VaccinesAgainst COVID-19

International Journal of Vaccine Theory, Practice, and Research 2(1), May 10, 2021 Page |


Worse Than the Disease? Reviewing Some Possible

Unintended Consequences of the mRNA Vaccines

Against COVID-19

AUTORS: Stephanie Seneff1 and Greg Nigh2

1Computer Science and Artificial Intelligence Laboratory, MIT, Cambridge MA, 02139, USA, E-mail:


2Naturopathic Oncology, Immersion Health, Portland, OR 97214, USA


Operation Warp Speed brought to market in the United States two mRNA vaccines, produced by Pfizer and

Moderna. Interim data suggested high efficacy for both of these vaccines, which helped legitimize Emergency

Use Authorization (EUA) by the FDA. However, the exceptionally rapid movement of these vaccines through

controlled trials and into mass deployment raises multiple safety concerns. In this review we first describe the

technology underlying these vaccines in detail. We then review both components of and the intended biological

response to these vaccines, including production of the spike protein itself, and their potential relationship to a

wide range of both acute and long-term induced pathologies, such as blood disorders, neurodegenerative

diseases and autoimmune diseases. Among these potential induced pathologies, we discuss the relevance of

prion-protein-related amino acid sequences within the spike protein. We also present a brief review of studies

supporting the potential for spike protein “shedding”, transmission of the protein from a vaccinated to an

unvaccinated person, resulting in symptoms induced in the latter. We finish by addressing a common point of

debate, namely, whether or not these vaccines could modify the DNA of those receiving the vaccination. While

there are no studies demonstrating definitively that this is happening, we provide a plausible scenario,

supported by previously established pathways for transformation and transport of genetic material, whereby

injected mRNA could ultimately be incorporated into germ cell DNA for transgenerational transmission. We

conclude with our recommendations regarding surveillance that will help to clarify the long-term effects of

these experimental drugs and allow us to better assess the true risk/benefit ratio of these novel technologies.

Keywords: antibody dependent enhancement, autoimmune diseases, gene editing, lipid nanoparticles, messenger

RNA, prion diseases, reverse transcription, SARS-CoV-2 vaccines


Unprecedented. This word has defined so much about 2020 and the pandemic related to SARSCoV-

2. In addition to an unprecedented disease and its global response, COVID-19 also initiated an

unprecedented process of vaccine research, production, testing, and public distribution (Shaw,

International Journal of Vaccine Theory, Practice, and Research 2(1), May 10, 2021 Page | 39

2021). The sense of urgency around combatting the virus led to the creation, in March 2020, of

Operation Warp Speed (OWS), then-President Donald Trump’s program to bring a vaccine against

COVID-19 to market as quickly as possible (Jacobs and Armstrong, 2020).

OWS established a few more unprecedented aspects of COVID-19. First, it brought the US

Department of Defense into direct collaboration with US health departments with respect to

vaccine distribution (Bonsell, 2021). Second, the National Institutes of Health (NIH) collaborated

with the biotechnology company Moderna in bringing an unprecedented type of vaccine against

infectious disease to market, one utilizing a technology based on messenger RNA (mRNA)

(National Institutes of Health, 2020).

The confluence of these unprecedented events has rapidly brought to public awareness the promise

and potential of mRNA vaccines as a new weapon against infectious diseases into the future. At the

same time, events without precedent are, by definition, without a history and context against which

to fully assess risks, hoped-for benefits, safety, and long-term viability as a positive contribution to

public health.

In this paper we will be briefly reviewing one

particular aspect of these unprecedented events,

namely the development and deployment of

mRNA vaccines against the targeted class of

infectious diseases under the umbrella of “SARSCoV-

2.” We believe many of the issues we raise

here will be applicable to any future mRNA

vaccine that might be produced against other

infectious agents, or in applications related to

cancer and genetic diseases, while others seem

specifically relevant to mRNA vaccines currently

being implemented against the subclass of corona

viruses. While the promises of this technology

have been widely heralded, the objectively

assessed risks and safety concerns have received

far less detailed attention. It is our intention to

review several highly concerning molecular

aspects of infectious disease-related mRNA

technology, and to correlate these with both

documented and potential pathological effects.

Vaccine Development

Development of mRNA vaccines against

infectious disease is unprecedented in many ways.

In a 2018 publication sponsored by the Bill and

Melinda Gates Foundation, vaccines were divided into three categories: Simple, Complex, and

Unprecedented (Young et al., 2018). Simple and Complex vaccines represented standard and

modified applications of existing vaccine technologies. Unprecedented represents a category of


Many aspects of Covid-19 and subsequent

vaccine development are unprecedented for a

vaccine deployed for use in the general

population. Some of these includes the


1. First to use PEG (polyethylene glycol) in an

injection (see text)

2. First to use mRNA vaccine technology

against an infectious agent

3. First time Moderna has brought any product

to market

4. First to have public health officials telling

those receiving the vaccination to expect an

adverse reaction

5. First to be implemented publicly with

nothing more than preliminary efficacy data

(see text)

6. First vaccine to make no clear claims about

reducing infections, transmissibility, or


7. First coronavirus vaccine ever attempted in


8. First injection of genetically modified

polynucleotides in the general population

International Journal of Vaccine Theory, Practice, and Research 2(1), May 10, 2021 Page | 40

vaccine against a disease for which there has never before been a suitable vaccine. Vaccines against

HIV and malaria are examples. As their analysis indicates, depicted in Figure 1, unprecedented

vaccines are expected to take 12.5 years to develop. Even more ominously, they have a 5% estimated

chance of making it through Phase II trials (assessing efficacy) and, of that 5%, a 40% chance of

making it through Phase III trials (assessing population benefit). In other words, an unprecedented

vaccine was predicted to have a 2% probability of success at the stage of a Phase III clinical trial. As

the authors bluntly put it, there is a “low probability of success, especially for unprecedented

vaccines.” (Young et al., 2018)

Figure 1. Launching innovative vaccines is costly and time-consuming, with a low probability of success, especially for

unprecedented vaccines (adapted from Young et al, 2018).

With that in mind, two years later we have an unprecedented vaccine with reports of 90-95%

efficacy (Baden et al. 2020). In fact, these reports of efficacy are the primary motivation behind

public support of vaccination adoption (U.S. Department of Health and Human Services, 2020).

This defies not only predictions, but also expectations. The British Medical Journal (BMJ) may be the

only prominent conventional medical publication that has given a platform to voices calling

attention to concerns around the efficacy of the COVID-19 vaccines. There are indeed reasons to

believe that estimations of efficacy are in need of re-evaluation.

Peter Doshi, an associate editor of the BMJ, has published two important analyses (Doshi 2021a,

2021b) of the raw data released to the FDA by the vaccine makers, data that are the basis for the

claim of high efficacy. Unfortunately, these were published to the BMJ’s blog and not in its peerreviewed

content. Doshi, though, has published a study regarding vaccine efficacy and the

questionable utility of vaccine trial endpoints in BMJ’s peer reviewed content (Doshi 2020).

A central aspect of Doshi’s critique of the preliminary efficacy data is the exclusion of over 3400

“suspected COVID-19 cases” that were not included in the interim analysis of the Pfizer vaccine

data submitted to the FDA. Further, a low-but-non-trivial percent of individuals in both Moderna

International Journal of Vaccine Theory, Practice, and Research 2(1), May 10, 2021 Page | 41

and Pfizer trials were deemed to be SARS-CoV-1-positive at baseline despite prior infection being

grounds for exclusion. For these and other reasons the interim efficacy estimate of around 95% for

both vaccines is suspect.

A more recent analysis looked specifically at the issue of relative vs. absolute risk reduction. While

the high estimates of risk reduction are based upon relative risks, the absolute risk reduction is a

more appropriate metric for a member of the general public to determine whether a vaccination

provides a meaningful risk reduction personally. In that analysis, utilizing data supplied by the

vaccine makers to the FDA, the Moderna vaccine at the time of interim analysis demonstrated an

absolute risk reduction of 1.1% (p= 0.004), while the Pfizer vaccine absolute risk reduction was

0.7% (p<0.000) (Brown 2021).

Others have brought up important additional questions regarding COVID-19 vaccine development,

questions with direct relevance to the mRNA vaccines reviewed here. For example, Haidere, et. al.

(2021) identify four “critical questions” related to development of these vaccines, questions that are

germane to both their safety and their efficacy:

• Will Vaccines Stimulate the Immune Response?

• Will Vaccines Provide Sustainable Immune Endurance?

• How Will SARS-CoV-2 Mutate?

• Are We Prepared for Vaccine Backfires?

Lack of standard and extended preclinical and clinical trials of the two implemented mRNA vaccines

leaves each of these questions to be answered over time. It is now only through observation of

pertinent physiological and epidemiological data generated by widescale delivery of the vaccines to

the general public that these questions will be resolved. And this is only possible if there is free

access to unbiased reporting of outcomes — something that seems unlikely given the widespread

censorship of vaccine-related information because of the perceived need to declare success at all


The two mRNA vaccines that have made it through phase 3 trials and are now being delivered to

the general population are the Moderna vaccine and the Pfizer-BioNTech vaccine. The vaccines

have much in common. Both are based on mRNA encoding the spike protein of the SARS-CoV-2

virus. Both demonstrated a relative efficacy rate of 94-95%. Preliminary indications are that

antibodies are still present after three months. Both recommend two doses spaced by three or four

weeks, and recently there are reports of annual booster injections being necessary (Mahose, 2021).

Both are delivered through muscle injection, and both require deep-freeze storage to keep the RNA

from breaking down. This is because, unlike double-stranded DNA which is very stable, singlestrand

RNA products are apt to be damaged or rendered powerless at warm temperatures and must

be kept extremely cold to retain their potential efficacy (Pushparajah et al., 2021). It is claimed by the

manufacturers that the Pfizer vaccine requires storage at -94 degrees Fahrenheit (-70 degrees

Celsius), which makes it very challenging to transport it and keep it cold during the interim before it

is finally administered. The Moderna vaccine can be stored for 6 months at -4 degrees Fahrenheit (-

20 degrees Celsius), and it can be stored safely in the refrigerator for 30 days following thawing

(Zimmer et al., 2021).

International Journal of Vaccine Theory, Practice, and Research 2(1), May 10, 2021 Page | 42

Two other vaccines that are now being administered under emergency use are the Johnson &

Johnson vaccine and the AstraZeneca vaccine. Both are based on a vector DNA technology that is

very different from the technology used in the mRNA vaccines. While these vaccines were also

rushed to market with insufficient evaluation, they are not the subject of this paper so we will just

describe briefly how they are developed. These vaccines are based on a defective version of an

adenovirus, a double-stranded DNA virus that causes the common cold. The adenovirus has been

genetically modified in two ways, such that it cannot replicate due to critical missing genes, and its

genome has been augmented with the DNA code for the SARS-CoV-2 spike protein. AstraZeneca’s

production involves an immortalized human cell line called Human Embryonic Kidney (HEK) 293,

which is grown in culture along with the defective viruses (Dicks et al., 2012). The HEK cell line

was genetically modified back in the 1970s by augmenting its DNA with segments from an

adenovirus that supply the missing genes needed for replication of the defective virus (Louis et al.,

1997). Johnson & Johnson uses a similar technique based on a fetal retinal cell line. Because the

manufacture of these vaccines requires genetically modified human tumor cell lines, there is the

potential for human DNA contamination as well as many other potential contaminants.

The media has generated a great deal of excitement about this revolutionary technology, but there

are also concerns that we may not be realizing the complexity of the body’s potential for reactions to

foreign mRNA and other ingredients in these vaccines that go far beyond the simple goal of tricking

the body into producing antibodies to the spike protein.

In the remainder of this paper, we will first describe in more detail the technology behind mRNA

vaccines. We devote several sections to specific aspects of the mRNA vaccines that concern us with

regard to potential for both predictable and unpredictable negative consequences. We conclude with

a plea to governments and the pharmaceutical industry to consider exercising greater caution in the

current undertaking to vaccinate as many people as possible against SARS-CoV-2.

Technology of mRNA Vaccines

In the early phase of nucleotide-based gene therapy development, there was considerably more

effort invested in gene delivery through DNA plasmids rather than through mRNA technology.

Two major obstacles for mRNA are its transient nature due to its susceptibility to breakdown by

RNAses, as well as its known power to invoke a strong immune response, which interferes with its

transcription into protein. Plasmid DNA has been shown to persist in muscle up to six months,

whereas mRNA almost certainly disappears much sooner. For vaccine applications, it was originally

thought that the immunogenic nature of RNA could work to an advantage, as the mRNA could

double as an adjuvant for the vaccine, eliminating the arguments in favor of a toxic additive like

aluminum. However, the immune response results not only in an inflammatory response but also

the rapid clearance of the RNA and suppression of transcription. So this idea turned out not to be


There was an extensive period of time over which various ideas were explored to try to keep the

mRNA from breaking down before it could produce protein. A major advance was the realization

that substituting methyl-pseudouridine for all the uridine nucleotides would stabilize RNA against

degradation, allowing it to survive long enough to produce adequate amounts of protein antigen

International Journal of Vaccine Theory, Practice, and Research 2(1), May 10, 2021 Page | 43

needed for immunogenesis (Liu, 2019). This form of mRNA delivered in the vaccine is never seen in

nature, and therefore has the potential for unknown consequences.

The Pfizer-BioNTech and Moderna mRNA vaccines are based on very similar technologies, where a

lipid nanoparticle encloses an RNA sequence coding for the full-length SARS-CoV-2 spike protein.

In the manufacturing process, the first step is to assemble a DNA molecule encoding the spike

protein. This process has now been commoditized, so it’s relatively straightforward to obtain a

DNA molecule from a specification of the sequence of nucleotides (Corbett et al., 2020). Following

a cell-free in vitro transcription from DNA, utilizing an enzymatic reaction catalyzed by RNA

polymerase, the single-stranded RNA is stabilized through specific nucleoside modifications, and

highly purified.

The company Moderna, in Cambridge, MA, is one of the developers of deployed mRNA vaccines

for SARS-CoV-2. Moderna executives have a grand vision of extending the technology for many

applications where the body can be directed to produce therapeutic proteins not just for antibody

production but also to treat genetic diseases and cancer, among others. They are developing a

generic platform where DNA is the storage element, messenger RNA is the “software” and the

proteins that the RNA codes for represent diverse application domains. The vision is grandiose and

the theoretical potential applications are vast (Moderna, 2020). The technology is impressive, but

manipulation of the code of life could lead to completely unanticipated negative effects, potentially

long term or even permanent.

SARS-CoV-2 is a member of the class of positive-strand RNA viruses, which means that they code

directly for the proteins that the RNA encodes, rather than requiring a copy to an antisense strand

prior to translation into protein. The virus consists primarily of the single-strand RNA molecule

packaged up inside a protein coat, consisting of the virus’s structural proteins, most notably the

spike protein, which facilitates both viral binding to a receptor (in the case of SARS-CoV-2 this is

the ACE2 receptor) and virus fusion with the host cell membrane. The SARS-CoV-2 spike protein is

the primary target for neutralizing antibodies. It is a class I fusion glycoprotein, and it is analogous to

haemagglutinin produced by influenza viruses and the fusion glycoprotein produced by syncytial

viruses, as well as gp160 produced by human immunodeficiency virus (HIV) (Corbett et al., 2020).

The mRNA vaccines are the culmination of years of research in exploring the possibility of using

RNA encapsulated in a lipid particle as a messenger. The host cell’s existing biological machinery is

co-opted to facilitate the natural production of protein from the mRNA. The field has blossomed in

part because of the ease with which specific oligonucleotide DNA sequences can be synthesized in

the laboratory without the direct involvement of living organisms. This technology has become

commoditized and can be done at large-scale, with relatively low cost. Enzymatic conversion of

DNA to RNA is also straightforward, and it is feasible to isolate essentially pure single-strand RNA

from the reaction soup (Kosuri and Church, 2014).

1. Considerations in mRNA Selection and Modification

While the process is simple in principle, the manufacturers of mRNA vaccines do face some

considerable technical challenges. The first, as we’ve discussed, is that extracellular mRNA itself can

induce an immune response which would result in its rapid clearance before it is even taken up by

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cells. So, the mRNA needs to be encased in a nanoparticle that will keep it hidden from the immune

system. The second issue is getting the cells to take up the nanoparticles. This can be solved in part

by incorporating phospholipids into the nanoparticle to take advantage of natural pathways of lipid

particle endocytosis. The third problem is to activate the machinery that is involved in translating

RNA into protein. In the case of SARS-CoV-2, the protein that is produced is the spike protein.

Following spike protein synthesis, antigen-presenting cells need to present the spike protein to T

cells, which will ultimately produce protective memory antibodies (Moderna, 2020). This step is not

particularly straightforward, because the nanoparticles are mostly taken up by muscle cells, which,

being immobile, are not necessarily equipped to launch an immune response. As we will see, the

likely scenario is that the spike protein is synthesized by muscle cells and then handed over to

macrophages acting as antigen-presenting cells, which then launch the standard B-cell-based

antibody-generating cascade response.

The mRNA that is enclosed in the vaccines undergoes several modification steps following its

synthesis from a DNA template. Some of these steps involve preparing it to look exactly like a

human mRNA sequence appropriately modified to support ribosomal translation into protein.

Other modifications have the goal of protecting it from breakdown, so that sufficient protein can be

produced to elicit an antibody response. Unmodified mRNA induces an immune response that leads

to high serum levels of interferon-α (IF- α), which is considered an undesirable response. However,

researchers have found that replacing all of the uridines in the mRNA with N-methyl-pseudouridine

enhances stability of the molecule while reducing its immunogenicity (Karikó et al. 2008; Corbett et

al., 2020). This step is part of the preparation of the mRNA in the vaccines, but, in addition, a 7-

methylguanosine “cap” is added to the 5’ end of the molecule and a poly-adenine (poly-A) tail,

consisting of 100 or more adenine nucleotides, is added to the 3’ end. The cap and tail are essential

in maintaining the stability of the mRNA within the cytosol and promoting translation into protein

(Schlake et al., 2012; Gallie, 1991).

Normally, the spike protein flips very easily from a pre-fusion configuration to a post-fusion

configuration. The spike protein that is in these vaccines has been tweaked to encourage it to favor a

stable configuration in its prefusion state, as this state provokes a stronger immune response

(Jackson et al., 2020). This was done via a “genetic mutation,” by replacing a critical two-residue

segment with two proline residues at positions 986 and 987, at the top of the central helix of the S2

subunit (Wrapp et al., 2020). Proline is a highly inflexible amino acid, so it interferes with the

transition to the fusion state. This modification provides antibodies much better access to the critical

site that supports fusion and subsequent cellular uptake. But might this also mean that the

genetically modified version of the spike protein produced by the human host cell following

instructions from the vaccine mRNA lingers in the plasma membrane bound to ACE2 receptors

because of impaired fusion capabilities? What might be the consequence of this? We don’t know.

Researchers in China published a report in Nature in August 2020 in which they presented data on

several experimental mRNA vaccines where the mRNA coded for various fragments and proteins in

the SARS-CoV-2 virus. They tested three distinct vaccine formulations for their ability to induce an

appropriate immune response in mice. The three structural proteins, S (spike), M and E are minimal

requirements to assemble a “virus-like particle” (VLP). Their hypothesis was that providing M and E

as well as the S spike protein in the mRNA code would permit the assembly of VLPs that might

International Journal of Vaccine Theory, Practice, and Research 2(1), May 10, 2021 Page | 45

elicit an improved immune response, because they more closely resemble the natural virus than S

protein exposed on the surface of cells that have taken up only the S protein mRNA from the

vaccine nanoparticles. They were also hoping that critical fragments of the spike protein would be

sufficient to induce immunity, rather than the entire spike protein, if viral-like particles could be

produced through augmentation with M and E (Lu et al., 2020).

They confirmed experimentally that a vaccine containing the complete genes for all three proteins

elicited a robust immune response that lasted for at least eight weeks following the second dose of

the vaccine. Its performance was far superior to that of a vaccine containing only the spike protein.

Disappointingly, a vaccine that contained only critical components of the spike protein, augmented

with the other two envelope proteins, elicited practically no response.

Moderna researchers have conducted similar studies with similar results. They concluded that the

spike protein alone was clearly inferior to a formulation containing RNA encoding all three envelope

proteins, and they hypothesized that this was due to the fact that all three proteins were needed to

allow the cell to release intact virus-like particles, rather than to just post the spike protein in the

plasma membrane. The spike protein alone failed to initiate a T cell response in animal studies,

whereas the formulation with all three proteins did (Corbett et al., 2020).

The two emergency-approved vaccines only contain mRNA code for spike protein (without E or

M), and there must have been a good reason for this decision, despite its observed poor

performance. It is possible that more sophisticated design of the lipid nanoparticle (see below)

resulted in the ability to have the lipids serve as an adjuvant (similar to aluminum that is commonly

added to traditional vaccines) while still protecting the RNA from degradation.

Another curious modification in the RNA code is that the developers have enriched the sequence in

cytosines and guanines (Cs and Gs) at the expense of adenines and uracils (As and Us). They have

been careful to replace only the third position in the codon in this way, and only when it does not

alter the amino acid map (Hubert, 2020). It has been demonstrated experimentally that GC-rich

mRNA sequences are expressed (translated into protein) up to 100-fold more efficiently than GCpoor

sequences (Kudla et al., 2006). So this appears to be another modification to further assure

synthesis of abundant copies of the spike protein. We do not know the unintended consequences of

this maneuver. Intracellular pathogens, including viruses, tend to have low GC content compared to

the host cell’s genome (Rocha and Danchin, 2020). So, this modification may have been motivated

in part by the desire to enhance the effectiveness of the deception that the protein is a human


All of these various modifications to the RNA are designed to make it resist breakdown, appear

more like a human messenger RNA protein-coding sequence, and efficiently translate into antigenic


2. Lipid Nanoparticle Construction

Lipid nanoparticles (LNPs), also known as liposomes, can encapsulate RNA molecules, protecting

them from enzymatic degradation by ribonucleases, and thus they form an essential ingredient of a

successful delivery method (Wadhwa et al., 2020; Xu et al., 2020). These artificial constructs closely

resemble exosomes. Exosomes are extracellullar vesicles secreted by cells and taken up by their

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neighbors, and they also often embed DNA or RNA. Thus, these nanoparticles can take advantage

of natural endocytosis processes that normally internalize extracellular exosomes into endosomes.

As the endosome acidifies to become a lysosome, the mRNA is released into the cytoplasm, and this

is where translation into protein takes place. Liposomes have actually been found to be more

successful at enhancing antigen presentation and maturation of dendritic cells, when compared to

fusion proteins that encapsulate virus-based vaccines (Norling et al., 2019).

The lipid nanoparticles (LNPs) in these vaccines are composed of ionizable cationic lipids,

phospholipids, cholesterol and polyethyleine glycol (PEG). Together, this mixture assembles into a

stable lipid bilayer around the mRNA molecule. The phospholipids in these experimental vaccines

consist of a phosphatidylcholine headgroup connected to two saturated alkyl tails through a glycerol

linker. The lipid used in these vaccines, named 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC),

has 18 repeat carbon units. The relatively long chain tends to form a gel phase rather than a fluid

phase. Molecules with shorter chains (such as a 12-carbon chain) tend to stay in a fluid phase

instead. Gel phase liposomes utilizing DSPC have been found to have superior performance in

protecting RNA from degradation because the longer alkyl chains are much more constrained in

their movements within the lipid domain. They also appear to be more efficient as an adjuvant,

increasing the release of the cytockines tumor necrosis factor- α (TNF- α), interleukin (IL)-6 and IL-

1β from exposed cells (Norling et al., 2019). However, their ability to induce an inflammatory

response may be the cause of the many symptoms people are experiencing, such as pain, swelling,

fever and sleepiness. A study published in bioRxiv verified experimentally that these ionizable

cationic lipids in lipid nanoparticles induce a strong inflammatory response in mice (Ndeupen et al.,


The current mRNA vaccines are delivered through intramuscular injection. Muscles contain a large

network of blood vessels where immune cells can be recruited to the injection site (Zeng et al.,

2020). Muscle cells generally can enhance an immune reaction once immune cells infiltrate, in

response to an adjuvant (Marino et al., 2011). Careful analysis of the response to an mRNA vaccine,

administered to mice, revealed that antigen is expressed initially within muscle cells and then

transferred to antigen-presenting cells, suggesting “cross-priming” as the primary path for initiating a

CD8 T cell response (Lazzaro et al., 2015). One can speculate that muscle cells make use of an

immune response that is normally used to deal with misfolded human proteins. Such proteins induce

upregulation of major histocompatibility complex (MHC) class II proteins, which then bind to the

misfolded proteins and transport them intact to the plasma membrane (Jiang et al., 2013).

The MHC-bound surface protein then induces an inflammatory response and subsequent infiltration

of antigen-presenting cells (e.g., dendritic cells and macrophages) into the muscle tissue, which then

take up the displayed proteins and carry them into the lymph system to present them to T cells.

These T cells can then finally launch the cascade that ultimately produces memory antibodies

specific to the protein. Muscle cells do express MHC class II proteins (Cifuentes-Diaz et al., 1992).

As contrasted with class I, class II MHC proteins specialize in transporting intact proteins to the

surface as opposed to small peptide sequences derived from the partial breakdown of the proteins

(Jiang et al., 2013).

An in vitro study on non-human primates demonstrated that radiolabeled mRNA moved from the

injection site into the draining lymph node and remained there for at least 28 hours. Antigen

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presenting cells (APCs) in both the muscle tissue as well as the draining lymph nodes were shown to

contain radiolabeled mRNA (Lindsay et al., 2019). Classical APCs include dendritic cells,

macrophages, Langerhans cells (in the skin) and B cells. Many of the side effects associated with

these vaccines involve pain and inflammation at the injection site, as would be expected given the

rapid infiltration of immune cells.

Lymphadenopathy is an inflammatory state in the lymph system associated with swollen lymph

nodes. Swollen lymph nodes in the arm pit (axillary lymphadenopathy) is a feature of metastatic

breast cancer. A paper published in 2021 described four cases of women who developed axillary

lymphadenopathy following a SARS-CoV-2 vaccine (Mehta et al., 2021). The authors urged caution

in misinterpreting this condition as an indicator requiring biopsy follow-up for possible breast

cancer. This symptom corroborates tracer studies showing that the mRNA vaccine is predominantly

taken up by APCs that then presumably synthesize the antigen (spike protein) from the mRNA and

migrate into the lymph system, displaying spike protein on their membranes.

A list of the most common adverse effects reported by the FDA that were experienced during the

Pfizer-BioNTech clinical trials include “injection site pain, fatigue, headache, muscle pain, chills,

joint pain, fever, injection site swelling, injection site redness, nausea, malaise, and

lymphadenopathy.” (US Food and Drug Administration, 2021).

We turn now to individual molecular and organ system concerns that arise with these mRNA


Adjuvants, Polyethylene Glycol, and Anaphylaxis

Adjuvants are vaccine additives intended to “elicit distinctive immunological profiles with regard to

the direction, duration, and strength of immune responses” from the vaccines to which they are

added (Liang et al., 2020). Alum or other aluminum compounds are most commonly utilized in

traditional vaccines, and they elicit a wide range of systemic immune activation pathways as well as

stromal cell activation at the site of the injection (Lambrecht et al., 2009; Danielsson & Eriksson,


An aluminum-based adjuvant was determined not to be optimal for a coronavirus vaccine, so other

solutions were sought (Liang et. al., 2020). A solution presented itself in the form of the widely used

pharmaceutical ingredient polyethylene glycol, or PEG. A limiting factor in the use of nucleic-acidbased

vaccines is the tendency for the nucleic acids to be quickly degraded by nuclease enzymes (Ho

et al., 2021). Regarding the RNAse enzymes targeting injected mRNA, these enzymes are widely

distributed both intracellularly (primarily within the lysosomes) (Fujiwara et al., 2017) and

extracellularly (Lu et al., 2018). To overcome this limitation, both mRNA vaccines currently

deployed against COVID-19 utilize lipid-based nanoparticles as delivery vehicles. The mRNA cargo

is placed inside a shell composed of synthetic lipids and cholesterol, along with PEG to stabilize the

mRNA molecule against degradation.

The vaccine produced by Pfizer/BioNTech creates nanoparticles from 2-[(polyethylene glycol)-

2000]-N,N-ditetradecylacetamide, or ALC-0159, commonly abbreviated simply as PEG (World

Health Organization, 2021, January 14). The Moderna vaccine contains another PEG variant, SM-

102, 1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol2000 (World Health Organization,

International Journal of Vaccine Theory, Practice, and Research 2(1), May 10, 2021 Page | 48

2021, January 19). For convenience we will abbreviate both PEG-modified lipids as PEG, and refer

to the vaccines as PEGylated according to standard nomenclature.

The lipid shell plays a triple role. First, it protects the genetic material from degradation prior to

cellular uptake. Second, the lipid shell, which also contains cholesterol, facilitates cellular uptake

through fusion with the lipid membrane of the cell and subsequent endocytosis of the lipid particle,

invoking naturally existing processes. And finally, it acts as an adjuvant (Ho et al., 2021). It is in this

latter role as immune stimulant that most concerns have been raised regarding the widespread use of

PEG in an injection therapy.

In an article published in May 2019, prior to large clinical trials involving these PEGylated vaccines,

Mohamed et. al. (2019) described a number of concerning findings regarding PEG and the

immunological activation it had been shown to produce, which includes humoral, cell-mediated, and

complement-based activation. They note that, paradoxically, large injection doses of PEG cause no

apparent allergic reaction. Small doses, though, can lead to dramatic pathological immune activation.

Vaccines employing PEGylation utilize micromolar amounts of these lipids, constituting this

potentially immunogenic low-dose exposure.

In animal studies it has been shown that complement activation is responsible for both anaphylaxis

and cardiovascular collapse, and injected PEG activates multiple complement pathways in humans

as well. The authors of one study conclude by noting that “This cascade of secondary mediators

substantially amplifies effector immune responses and may induce anaphylaxis in sensitive

individuals. Indeed, recent studies in pigs have demonstrated that systemic complement activation

(e.g., induced following intravenous injection of PEGylated liposomes) can underlie cardiac

anaphylaxis where C5a played a causal role.” (Hamad et al., 2008) It is also important to note that

anaphylactoid shock in pigs occurred not with first injected exposure, but following second injected

exposure (Kozma et al., 2019).

The presence of antibodies against PEG is widespread in the population (Zhou et al., 2020). Yang

and Lai (2015) found that around 42% of blood samples surveyed contained anti-PEG antibodies,

and they warn that these could have important consequences for any PEG-based therapeutics

introduced. Hong et. al. (2020) found anti-PEG antibodies with a prevalence up to 72% in

populations with no prior exposure to PEG-based medical therapy. Lila et. al. (2018) note that the

“existence of such anti-PEG antibodies has been intimately correlated with an impairment of

therapeutic efficacy in tandem with the development of severe adverse effects in several clinical

settings employing PEGylated-based therapeutics.”

Anaphylaxis to vaccines has previously been assumed to be rare based on the frequency of such

events reported to VAERS, a database established by the Centers for Disease Control and

Prevention in 1990 for reporting of adverse events related to vaccines (Centers for Disease Control

and Prevention, 1990; Su et al., 2019). While rare, anaphylaxis can be life-threatening, so it is

important to monitor for the possibility in the short period following vaccination (McNeil et al.,


Sellaturay et. al., after reviewing 5 cases of anaphylaxis they link to PEG exposure, one near-fatal and

involving cardiac arrest, write, “PEG is a high-risk ’hidden’ allergen, usually unsuspected and can

cause frequent allergic reactions due to inadvertent re-exposure. Allergy investigation carries the risk

International Journal of Vaccine Theory, Practice, and Research 2(1), May 10, 2021 Page | 49

of anaphylaxis and should be undertaken only in specialist drug allergy centres.” (Sellaturay et al.,

2020). In fact it has already been demonstrated that pre-existing antibodies to PEG are linked to

more common and more severe reactions upon re-exposure (Ganson et al., 2016).

Is anaphylaxis upon exposure to PEG happening with a frequency relevant to public health?

Numerous studies have now documented the phenomenon (Lee et al., 2015; Povsic et al., 2016;

Wylon et al., 2016). Anaphylactic reactions to the mRNA vaccines are widely reported in the media

(Kelso, 2021) and, as noted above, have been frequently reported in the VAERS database (690

reports of anaphylaxis following SARS-CoV-2 vaccines up to January 29, 2021). There are also some

initial case studies published in the peer-reviewed literature (Garvey & Nasser, 2020; CDC COVID-

19 Response Team, 2021, January 15). Anaphylaxis reactions to vaccines prior to these COVID-19

vaccines were generally reported at rates less than 2 cases per million vaccinations (McNeil et al.,

2016), while the current rate with the COVID-19 vaccinations was reported by the CDC to be more

than 11 cases per million (CDC COVID-19 Response Team, 2021, January 29). However, a

published prospective study on 64,900 medical employees, where their reactions to their first mRNA

vaccination were carefully monitored, found that 2.1% of the subjects reported acute allergic

reactions. A more extreme reaction involving anaphylaxis occurred at a rate of 247 per million

vaccinations (Blumenthal et al., 2021). This is more than 21 times as many as were initially reported

by the CDC. The second injection exposure is likely to cause even larger numbers of anaphylactic


mRNA Vaccines, Spike Proteins, and Antibody-Dependent Enhancement


ADE is an immunological phenomenon first described in 1964 (Hawkes et al., 1964). In that

publication Hawkes described a set of experiments in which cultures of flavivirus were incubated

with avian sera containing high titers of antibodies against those viruses. The unexpected finding

was that, with increasingly high dilutions of the antibody-containing sera, cell infectivity was enhanced.

Lack of an explanation for how this could happen is likely responsible for its being largely ignored

for almost 20 years (Morens et al., 1994).

Multiple pathways have been proposed through which antibodies both directly and indirectly

participate in the neutralization of infections (Lu et al., 2018b). ADE is a special case of what can

happen when low, non-neutralizing levels of either specific or cross-reactive antibodies against a

virus are present at the time of infection. These antibodies might be present due to prior exposure to

the virus, exposure to a related virus, or due to prior vaccination against the virus. Upon reinfection,

antibodies in insufficient numbers to neutralize the virus nevertheless bind to the virus. These

antibodies then dock at the Fc receptor on cell surfaces, facilitating viral entry into the cell and

subsequently enhancing the infectivity of the virus (Wan et. al., 2020).

ADE is believed to underlie the more severe dengue fever often observed in those with previous

exposure (Beltramello et al., 2010), and might also play a role in more severe disease among those

previously vaccinated against the disease (Shukla et al., 2020). ADE is also believed to play a role in

Ebola (Takada et al., 2003), zika virus infection (Bardina et al., 2017), and other flavivirus infections

(Campos et al., 2020).

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In an extended correspondence published in Nature Biotechnology, Eroshenko et. al. offer a

comprehensive review of evidence suggesting that ADE could become manifest with any

vaccinations employed against SARS-CoV-2. Importantly, they note that ADE has been observed

with coronavirus vaccines tested in both in vitro and in vivo models (Eroshenko et al., 2020). Others

have warned about the same possibility with SARS-CoV-2 vaccines. A theory for how ADE might

occur in the case of a SARS-CoV-2 vaccine suggests that non-neutralizing antibodies form immune

complexes with viral antigens to provoke excessive secretion of pro-inflammatory cytokines, and, in

the extreme case, a cytokine storm causing widespread local tissue damage (Lee et al., 2020). One

extensive review of ADE potentially associated with SARS-CoV-2 vaccines noted, “At present, there

are no known clinical findings, immunological assays or biomarkers that can differentiate any severe

viral infection from immune-enhanced disease, whether by measuring antibodies, T cells or intrinsic

host responses” (Arvin et al. 2020; Liu et al., 2019). We will return to this point again below.

Preexisting immunoglobulin G (IgG) antibodies, induced by prior vaccination, contribute to severe

pulmonary damage by SARS-CoV in macaques (Liu et al., 2019). Peron and Nakaya (2020) provide

evidence suggesting that the much more diverse range of prior exposures to coronaviruses

experienced by the elderly might predispose them to ADE upon exposure to SARS-CoV-2. A

concerning pre-print article reported that plasma from 76% of patients who had recovered from

severe COVID-19 disease, when added to cultures of SARS-CoV-2 and susceptible cells, exhibited

enhanced ability for SARS-CoV-2 viral infection of Raji cells (Wu et al., 2020). The authors note that

“the antibody titers [against the spike protein] were higher in elderly patients of COVID-19, and

stronger antibody response was associated with delayed viral clearance and increased disease severity

in patients. Hence it is reasonable to speculate that S protein-specific antibodies may contribute to

disease severity during SARS-CoV-2 infection.” (Wu et al., 2020)

It has been reported that all three US vaccine manufacturers – Moderna, Pfizer, and Johnson &

Johnson – are working to develop booster shots (Zaman 2021).With tens of millions of young adults

and even children now with vaccine-induced coronavirus spike protein antibodies, there exists the

possibility of triggering ADE related to either future SARS-CoV-2 infection or booster injection

among this younger population. Time will tell.

The mRNA vaccines ultimately deliver the highly antigenic spike protein to antigen-presenting cells.

As such, monoclonal antibodies against the spike protein are the expected outcome of the currently

deployed mRNA vaccines. Human spike protein monoclonal antibodies were found to produce high

levels of cross-reactive antibodies against endogenous human proteins (Vojdani et. al., 2021;

reviewed in more detail below). Given evidence only partially reviewed here, there is sufficient

reason to suspect that antibodies to the spike protein will contribute to ADE provoked by prior

SARS-CoV-2 infection or vaccination, which may manifest as either acute or chronic autoimmune

and inflammatory conditions. We have noted above that it is not possible to distinguish an ADE

manifestation of disease from a true, non-ADE viral infection. In this light it is important to

recognize that, when diseases and deaths occur shortly after vaccination with an mRNA vaccine, it

can never be definitively determined, even with a full investigation, that the vaccine reaction was not

a proximal cause.

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Pathogenic Priming, Multisystem Inflammatory Disease, and Autoimmunity

Pathogenic priming is a concept that is similar in outcome to ADE, but different in the underlying

mechanism. We discuss it here as a unique mechanism through which the mRNA vaccines could

provoke associated pathologies.

In April 2020 an important paper was published regarding the potential for self-reactive antibodies

to be generated following exposure to the spike protein and other antigenic epitopes spread over the

length of SARS-CoV-2. Lyons-Weiler (2020) coined the phrase “pathogen priming” because he

believed the more commonly used “immune enhancement” fails to capture the severity of the

condition and its consequences. In his in silico analysis, Lyons-Weiler compared all antigenic SARSCoV-

2 protein epitopes flagged in the SVMTriP database (http://sysbio.unl.edu/SVMTriP/) and

searched the p-BLAST database (https://blast.ncbi.nlm.nih.gov/Blast.cgi) for homology between

those epitopes and endogenous human proteins. Of the 37 SARS-CoV-2 proteins analyzed, 29 had

antigenic regions. All but one of these 29 had homology with human proteins (putative selfantigens)

and were predicted to be autoreactogenic. The largest number of homologies were

associated with the spike (S) protein and the NS3 protein, both having 6 homologous human


A functional analysis of the endogenous human proteins homologous with viral proteins found that

over 1/3 of them are associated with the adaptive immune system. The author speculates that prior

virus exposure or prior vaccination, either of which could initiate antibody production that targets

these endogenous proteins, may be playing a role in the development of more severe disease in the

elderly in particular. In this case the pre-existing antibodies act to suppress the adaptive immune

system and lead to more severe disease.

Another group (Ehrenfeld et. al., 2020), in a paper predominantly about the wide range of

autoimmune diseases found in association with a prior SARS-CoV-2 infection, also investigated how

the spike protein could trigger such a range of diseases. They report, in Table 1 of that reference,

strings of heptapeptides within the human proteome that overlap with the spike protein generated

by SARS-CoV-2. They identified 26 heptapeptides found in humans and in the spike protein. It is

interesting to note that 2 of the 26 overlapping heptapeptides were found to be sequential, a

strikingly long string of identical peptides to be found in common between endogenous human

proteins and the spike protein. Commenting on the overlapping peptides they had discovered and

the potential for this to drive many types of autoimmunity simultaneously, they comment, “The

clinical scenario that emerges is upsetting.” Indeed, it is.

In May of 2020 another important paper in this regard was published by Vojdani and Kharrazian

(2020). The authors used both mouse and rabbit monoclonal antibodies against the 2003 SARS

spike protein to test for reactivity against not only the spike protein of SARS-CoV-2, but also against

several endogenous human proteins. They discovered that there was a high level of binding not only

with the SARS-CoV-2 spike protein, but against a wide range of endogenous proteins. “[W]e found

that the strongest reactions were with transglutaminase 3 (tTG3), transglutaminase 2 (tTG2), ENA,

myelin basic protein (MBP), mitochondria, nuclear antigen (NA), α-myosin, thyroid peroxidase

(TPO), collagen, claudin 5+6, and S100B.” (Vojdani and Kharrazian, 2020).

International Journal of Vaccine Theory, Practice, and Research 2(1), May 10, 2021 Page | 52

These important findings need to be emphasized. Antibodies with a high binding affinity to SARSCoV-

2 spike and other proteins also have a high binding affinity with tTG (associated with Celiac

Disease), TPO (Hashimoto’s thyroiditis), myelin basic protein (multiple sclerosis), and several

endogenous proteins. Unlike the autoimmune process associated with pathogen priming, these

autoimmune diseases typically take years to manifest symptomatically.

The autoantibodies generated by the spike protein predicted by Lyons-Weiler (2020) and described

above were confirmed with an in vitro study published more recently. In this follow-on paper,

Vojdani et. al., (2021) looked again at the issue of cross-reactivity of antibodies, this time using

human monoclonal antibodies (mAbs) against the SARS-CoV-2 spike protein rather than mouse and

rabbit mAbs. Their results confirmed and extended their prior findings. “At a cutoff of 0.32 OD

[optical density], SARS-CoV-2 membrane protein antibody reacted with 18 out of the 55 tested

antigens.” These 18 endogenous antigens encompass reactivity to tissue in liver, mitochondria, the

nervous and digestive system, the pancreas, and elsewhere in the body.

In a report on multisystem inflammatory syndrome in children (MIS-C), Carter et. al. (2020) studied

23 cases. Seventeen of 23 (68%) patients had serological evidence of prior SARS-CoV-2 infection.

Of the three antibodies assessed in the patient population (nucleocapsid, RBD, and spike), IgG spike

protein antibody optical density (which quantifies antibody concentrations against a standardized

curve (Wikipedia, 2021)), was highest (see Figure 1d in Carter et al., 2020).

MIS-C is now commonly speculated to be an example of immune priming by prior exposure to

SARS-CoV-2 or to other coronaviruses. Buonsenso et. al. (2020) reviewed multiple immunologic

similarities between MIS-C and disease related to prior β-hemolytic Group A streptococcal infection

(GAS). The authors write, “We can speculate that children’s multiple exposition to SARS-CoV-2

with parents with COVID-19 can work as a priming of the immune system, as happens with GAS

infection and, in genetically predisposed children, lead to [MIS-C] development. Another hypothesis

is that previous infections with other coronaviruses, much more frequent in the pediatric population,

may have primed the child immune system to SARS-CoV-2 virus.”

In June 2019 Galeotti and Bayry (2020) reviewed the occurrence of both autoimmune and

inflammatory diseases in patients with COVID-19. They focus their analysis on MIS-C. After

reviewing several previously published reports of a temporal link between COVID-19 and onset of

MIS-C and describing a number of possible mechanistic connections between the two, the authors

noted that no causal link had been established. In a somewhat prescient recommendation, they

wrote, “A fine analysis of homology between various antigens of SARS-CoV-2 and self-antigens, by

use of in silico approaches and validation in experimental models, should be considered in order to

confirm this hypothesis.” It is precisely this type of in silico analysis carried out by Lyons-Weiler

(2020) and by Ehrenfeld et. al. (2020) described in the opening paragraphs of this section which

found the tight homology between viral antigens and self-antigens. While this may not definitively

confirm the causal link hypothesized by Galeotti and Bayry, it is strong supporting evidence.

Autoimmunity is becoming much more widely recognized as a sequela of COVID-19. There are

multiple reports of previously healthy individuals who developed diseases such as idiopathic

thrombocytopenic purpura, Guillain-Barré syndrome and autoimmune haemolytic anaemia (Galeotti

and Bayry, 2020). There are three independent case reports of systemic lupus erythemosus (SLE)

International Journal of Vaccine Theory, Practice, and Research 2(1), May 10, 2021 Page | 53

with cutaneous manifestations following symptomatic COVID-19. In one case a 39-year-old male

had SLE onset two months following outpatient treatment for COVID-19 (Zamani et.al., 2021).

Another striking case of rapidly progressing and fatal SLE with cutaneous manifestations is

described by Slimani et.al. (2021).

Autoantibodies are very commonly found in COVID-19 patients, including antibodies found in

blood (Vlachoyiannopoulos et. al., 2020) and cerebrospinal fluid (CFS) (Franke et. al., 2021).

Though SARS-CoV-2 is not found in the CSF, it is theorized that the autoantibodies created in

response to SARS-CoV-2 exposure may lead to at least some portion of the neurological

complications documented in COVID-19 patients. One important Letter to the Editor submitted to

the journal Arthritis & Rheumatology by Bertin et. al. (2020) noted the high prevalence and strong

association (p=0.009) of autoantibodies against cardiolipin in COVID-19 patients with severe


Zuo et. al. (2020) found anti-phospholipid autoantibodies in 52% of hospitalized COVID-19

patients and speculated that these antibodies contribute to the high incidence of coagulopathies in

these patients. Schiaffino et. al. (2020) reported that serum from a high percentage of hospitalized

COVID-19 patients contained autoantibodies reactive to the plasma membrane of hepatocytes and

gastric cells. One patient with Guillain-Barre Syndrome was found to have antibody reactivity in

cerebrospinal fluid (CFS), leading the authors to suggest that cross-reactivity with proteins in the

CFS could lead to neurological complications seen in some COVID-19 patients. In a more recent

review, Gao et. al. (2021) noted high levels of autoantibodies in COVID-19 patients across multiple

studies. They conclude, “[O]ne of the potential side effects of giving a mass vaccine could be an

mergence [sic] of autoimmune diseases especially in individuals who are genetically prone for


A recent publication compiles a great deal of evidence that autoantibodies against a broad range of

receptors and tissue can be found in individuals who have had previous SARS-CoV-2 infection. “All

31 former COVID-19 patients had between 2 and 7 different GPCR-fAABs [G-protein coupled

receptor functional autoantibodies] that acted as receptor agonists.” (Wallukat et. al. 2021) The

diversity of GPCR-fAABs identified, encompassing both agonist and antagonist activity on target

receptors, strongly correlated with a range of post-COVID-19 symptoms, including tachycardia,

bradycardia, alopecia, attention deficit, PoTS, neuropathies, and others.

The same study, referencing the autoantibodies predicted by Lyons-Weiler (2020) mentioned above,

notes with obvious grave concern: “The Sars-CoV-2 spike protein is a potential epitopic target for

biomimicry-induced autoimmunological processes [25]. Therefore, we feel it will be extremely

important to investigate whether GPCR-fAABs will also become detectable after immunisation by

vaccination against the virus.”

We have reviewed the evidence here that the spike protein of SARS-CoV-2 has extensive sequence

homology with multiple endogenous human proteins and could prime the immune system toward

development of both auto-inflammatory and autoimmune disease. This is particularly concerning

given that the protein has been redesigned with two extra proline residues to potentially impede its

clearance from the circulation through membrane fusion. These diseases could present acutely and

International Journal of Vaccine Theory, Practice, and Research 2(1), May 10, 2021 Page | 54

over relatively short timespans such as with MIS-C or could potentially not manifest for months or

years following exposure to the spike protein, whether via natural infection or via vaccination.

Many who test positive for COVID-19 express no symptoms. The number of asymptomatic, PCRpositive

cases varies widely between studies, from a low of 1.6% to a high of 56.5% (Gao et. al.,

2020). Those who are insensitive to COVID-19 probably have a very strong innate immune system.

The healthy mucosal barrier’s neutrophils and macrophages rapidly clear the viruses, often without

the need for any antibodies to be produced by the adaptive system. However, the vaccine

intentionally completely bypasses the mucosal immune system, both through its injection past the

natural mucosal barriers and its artificial configuration as an RNA-containing nanoparticle. As noted

in Carsetti (2020), those with a strong innate immune response almost universally experience either

asymptomatic infection or only mild COVID-19 disease presentation. Nevertheless, they might face

chronic autoimmune disease, as described previously, as a consequence of excessive antibody

production in response to the vaccine, which was not necessary in the first place.

The Spleen, Platelets and Thrombocytopenia

Dr. Gregory Michael, an obstetrician in Miami Beach, died of a cerebral hemorrhage 16 days after

receiving the first dose of the Pfizer/BioNTech COVID-19 vaccine. Within three days of the

vaccine, he developed idiopathic thrombocytopenic purpura (ITP), an autoimmune disorder in

which the immune cells attack and destroy the platelets. His platelet count dropped precipitously,

and this caused an inability to stop internal bleeding, leading to the stroke, as described in an article

in the New York Times (Grady and Mazzei, 2021). The New York Times followed up with a second

article that discussed several other cases of ITP following SARS-CoV-2 vaccination (Grady, 2021),

and several other incidences of precipitous drop of platelets and thrombocytopenia following SARSCoV-

2 vaccination have been reported in the Vaccine Adverse Event Reporting System (VAERS).

1. Biodistribution of mRNA Vaccines

Several studies on mRNA-based vaccines have confirmed independently that the spleen is a major

center of activity for the immune response. A study on an mRNA-based influenza virus vaccine is

extremely relevant for answering the question of the biodistribution of the mRNA in the vaccine.

This vaccine, like the SARS-CoV-2 vaccines, was designed as lipid nanoparticles with modified RNA

coding for hemagglutinin (the equivalent surface fusion protein to the spike protein in corona

viruses), and was administered through muscular injection. The concentration of mRNA was tracked

over time in various tissue samples, and the maximum concentration observed at each site was

recorded. Not surprisingly, the concentration was highest in the muscle at the injection site (5,680

ng/mL). This level decreased slowly over time, reaching half the original value at 18.8 hours

following injection. The next highest level was observed in the proximal lymph node, peaking at

2,120 ng/mL and not dropping to half this value until 25.4 hours later. Among organs, the highest

levels by far were found in the spleen (86.69 ng/mL) and liver (47.2 ng/mL). Elsewhere in the body

the concentration was at 100- to 1,000-fold lower levels. In particular, distal lymph nodes only had a

peak concentration of 8 ng/mL. They concluded that the mRNA distributes from the injection site

to the liver and spleen via the lymphatic system, ultimately reaching the general circulation. This

likely happens through its transport inside macrophages and other immune cells that take it up at the

International Journal of Vaccine Theory, Practice, and Research 2(1), May 10, 2021 Page | 55

muscular injection site. Disturbingly, it also reaches into the brain, although at much lower levels

(Bahl et al., 2017). The European Medicines Agency assessment report for the Moderna vaccine also

noted that mRNA could be detected in the brain following intramuscular administration at about

2% of the level found in the plasma (European Medicines Agency, 2021).

In another experiment conducted to track the biodistribution pathway of RNA vaccines, a rabies

RNA vaccine was administered intramuscularly to rats in a single dose. The vaccine included a code

for an immunogenic rabies protein as well as the code for RNA polymerase and was formulated as

an oil-in-water nanoemulsion. Thus, it is not entirely representative of the SARS-CoV-2 mRNA

vaccines. Nevertheless, its intramuscular administration and its dependence on RNA uptake by

immune cells likely means that it would migrate through the tissues in a similar pathway as the

SARS-CoV-2 vaccine. The authors observed an enlargement of the draining lymph nodes, and tissue

studies revealed that the rabies RNA appeared initially at the injection site and in the draining lymph

nodes within one day, and was also found in blood, lungs, spleen and liver (Stokes et al., 2020).

These results are consistent with the above study on influenza mRNA vaccines.

Finally, a study comparing luciferase-expressing mRNA nanoparticles with luciferase-expressing

mRNA dendritic cells as an alternative approach to vaccination revealed that the luciferase signal

reached a broader range of lymphoid sites with the nanoparticle delivery mechanism. More

importantly, the luciferase signal was concentrated in the spleen for the nanoparticles compared to

dominance in the lungs for the dendritic cells (Firdessa-Fite and Creuso, 2020).

2. Immune Thrombocytopenia

Immune thrombocytopenia (ITP) has emerged as an important complication of COVID-19

(Bhattacharjee and Banerjee, 2020). In many cases, it emerges after full recovery from the disease,

i.e, after the virus has been cleared, suggesting it is an autoimmune phenomenon. A likely pathway

by which ITP could occur following vaccination is through the migration of immune cells carrying a

cargo of mRNA nanoparticles via the lymph system into the spleen. These immune cells would

produce spike protein according to the code in the nanoparticles, and the spike protein would

induce B cell generation of IgG antibodies to it.

ITP appears initially as petechiae or purpura on the skin, and/or bleeding from mucosal surfaces. It

has a high risk of fatality through haemorrhaging and stroke. ITP is characterized by both increased

platelet destruction and reduced platelet production, and autoantibodies play a pivotal role (Sun and

Shan, 2019). Platelets are coated by anti-platelet antibodies and immune complexes, and this induces

their clearance by phagocytes.

Particularly under conditions of impaired autophagy, the resulting signaling cascade can also result in

suppression of production of megakaryocytes in the bone marrow, which are the precursor cells for

platelet production (Sun and Shan, 2019). A case study of a patient diagnosed with COVID-19 is

revealing because he developed sudden onset thrombocytopenia a couple of days after he had been

released from the hospital based on a negative COVID-19 nucleic acid test. Following this

development, it was verified that the patient had a reduced number of platelet-producing

megakaryocytes, while autoimmune antibodies were negative, suggesting a problem with platelet

production rather than platelet destruction (Chen et al., 2020).

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Autophagy is essential for clearing damaged proteins, organelles, and bacterial and viral pathogens.

Alterations in autophagy pathways are emerging as a hallmark of the pathogenesis of many

respiratory viruses, including influenza virus, MERS-CoV, SARS-CoV and, importantly, SARS-CoV-

2 (Limanaqi et al., 2020). Autophagy is surely critical in the clearance of spike protein produced by

immune cells programmed to produce it through the mRNA vaccines.

One can speculate that impaired autophagy prevents clearance of the spike protein produced by

macrophages from the vaccine mRNA. As we will show later, platelets possess autophagic proteins

and use autophagy to clear viruses. Impaired autophagy is a characteristic feature of ITP, and it may

be key to the autoimmune attack on the platelets (Wang et al., 2019).

3. A Critical Role for the Spleen

The spleen is the largest secondary lymphoid organ in humans and it contains as much as 1/3 of the

body’s platelet supplies. The spleen is the primary site for platelet destruction during ITP, as it

controls the antibody response against platelets. The two main autoantibodies associated with ITP

are against immunoglobulin G (IgG) and the glycoprotein (GP) IIb/IIIa complex on platelets

(Aslam et al., 2016).

The spleen plays a central role in the clearance of foreign antigens and the synthesis of IgG by B

cells. Upon exposure to an antigen, such as the spike protein, neutrophils in the marginal zone of the

spleen acquire the ability to interact with B cells, inducing antibody production (Puga et al., 2011).

This is likely crucial for successful vaccination outcome. The pseudouridine modification of mRNA

is important for assuring RNA survival long enough for it to reach the spleen. In an experiment on

injection of mRNA nanoparticles into mice, both the delivered mRNA and the encoded protein

could be detected in the spleen at 1, 4, and 24 hours after injection, at significantly higher levels than

when non-modified RNA was used (Karikó et al., 2008).

A sophisticated platelet-neutrophil cross-communication mechanism in the spleen can lead to

thrombocytopenia, mediated by a pathological response called NETosis. Platelet-TLR7 (toll-like

receptor 7) recognizes influenza particles in circulation and leads to their engulfment and

endocytosis by the platelets. After engulfing the viruses, the platelets stimulate neutrophils to release

their DNA within Neutrophil Extracellular Traps (NETs) (Koupenova et al., 2019), and the DNA,

in excessive amounts, launches a prothrombotic cascade.

4. Lessons from Influenza

The influenza virus, like the corona virus, is a single-strand RNA virus. Thrombocytopenia is a

common complication of influenza infection, and its severity predicts clinical outcomes in critically

ill patients (Jansen et al., 2020). Platelets contain abundant glycoproteins in their membranes which

act as receptors and support adhesion to the endothelial wall. Autoantibodies against platelet

glycoproteins are found in the majority of patients with autoimmune thrombocytopenia (Lipp et al.,

1998). The influenza virus binds to cells via glycoproteins, and it releases an enzyme called

neuraminidase that can break down the glycosaminoglycans bound to the glycoproteins and release

them. This action likely exposes the platelet glycoproteins to B cells, inducing autoantibody

production. Neuraminidase expressed by the pathogen Streptococcus pneumoniae has been shown

to desialylate platelets, leading to platelet hyperactivity (Kullaya et al., 2018).

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Platelets appear to play an important role in viral clearance. Within one minute after platelets were

incubated together with influenza viruses, the viruses had already attached to the platelets.

Subsequent internalization, possibly by phagocytosis, peaked at 30 minutes (Jansen et al., 2020).

The SARS-CoV-2 spike protein binds sialic acid, which means it could attach to glycoproteins in the

platelet membranes (Baker et al., 2020). There is a structural similarity between the S1 spike protein

in SARS CoV and neuraminidase expressed by the influenza virus, which might mean that the spike

protein possesses neuraminidase activity (Zhang et al., 2004). Several viruses express neuraminidase,

and it generally acts enzymatically to catabolize the glycans in glycoproteins through desialylation.

Thus, it seems plausible that a dangerous cascade leading to ITP could ensue following mRNA

vaccination, even with no live virus present, particularly in the context of impaired autophagy.

Immune cells in the arm muscle take up the RNA particles and circulate within the lymph system,

accumulating in the spleen. There, the immune cells produce abundant spike protein, which binds to

the platelet glycoproteins and desialylates them. Platelet interaction with neutrophils causes NETosis

and the launch of an inflammatory cascade. The exposed glycoproteins become targets for

autoimmune antibodies that then attack and remove the platelets, leading to a rapid drop in platelet

counts, and a life-threatening event.

Activation of Latent Herpes Zoster

An observational study conducted at Tel Aviv Medical Center and the Carmel Medical Center in

Haifa, Israel, found a significantly increased rate of herpes zoster following the Pfizer vaccination

(Furer 2021). This observational study monitored patients with pre-existing autoimmune

inflammatory rheumatic diseases (AIIRD). Among the 491 patients with AIIRD over the study

period, 6 (1.2%) were diagnosed with herpes zoster as a first-ever diagnosis between 2 days and 2

weeks after either the first or second vaccination. In the control group of 99 patients there were no

herpes zoster cases identified.

The CDC’s VAERS database, queried on April 19, 2021, contains 278 reports of herpes zoster

following either the Moderna or Pfizer vaccinations. Given the documented underreporting to

VAERS (Lazarus et al. 2010), and given the associational nature of VAERS reports, it is not possible

to prove any causal link between the vaccinations and the zoster reports. However, we believe the

occurrence of zoster is another important ‘signal’ in VAERS.

This increased risk to shingles, if valid, may have important broader implications. Multiple studies

have shown that patients with either primary or acquired immune deficiency are more susceptible to

severe herpes zoster infection (Ansari et al., 2020). This suggests that the mRNA vaccines may be

suppressing the innate immune response. There is cross-talk between TNF- α and type I interferon

in autoimmune disease, wherein each suppresses the other (Palucka et al., 2005). Type I interferon

inhibits varicella-zoster virus replication (Ku et al., 2016). TNF- α is sharply upregulated in an

inflammatory response, which is induced by the lipid nanoparticles in the vaccine. Its upregulation is

also associated with the chronic inflammatory state of rheumatoid arthritis (Matsuno et al., 2002).

Exuberant TNF-α expression following vaccination may be interfering with the dendritic cell INF-α

response that keeps latent herpes zoster in check.

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Spike Protein Toxicity

The picture is now emerging that SARS-CoV-2 has serious effects on the vasculature in multiple

organs, including the brain vasculature. As mentioned earlier, the spike protein facilitates entry of

the virus into a host cell by binding to ACE2 in the plasma membrane. ACE2 is a type I integral

membrane protein that cleaves angiotensin II into angiotensin(1-7), thus clearing angiotensin II and

lowering blood pressure. In a series of papers, Yuichiro Suzuki in collaboration with other authors

presented a strong argument that the spike protein by itself can cause a signaling response in the

vasculature with potentially widespread consequences (Suzuki, 2020; Suzuki et al., 2020; Suzuki et al.,

2021; Suzuki and Gychka, 2021). These authors observed that, in severe cases of COVID-19, SARSCoV-

2 causes significant morphological changes to the pulmonary vasculature. Post-mortem analysis

of the lungs of patients who died from COVID-19 revealed histological features showing vascular

wall thickening, mainly due to hypertrophy of the tunica media. Enlarged smooth muscle cells had

become rounded, with swollen nuclei and cytoplasmic vacuoles (Suzuki et al., 2020). Furthermore,

they showed that exposure of cultured human pulmonary artery smooth muscle cells to the SARSCoV-

2 spike protein S1 subunit was sufficient to promote cell signaling without the rest of the virus


Follow-on papers (Suzuki et al., 2021,

Suzuki and Gychka, 2021) showed that

the spike protein S1 subunit

suppresses ACE2, causing a condition

resembling pulmonary arterial

hypertension (PAH), a severe lung

disease with very high mortality. Their

model is depicted here in Figure 2.

Ominously, Suzuki and Gychka (2021)

wrote: “Thus, these in vivo studies

demonstrated that the spike protein of

SARS-CoV-1 (without the rest of the

virus) reduces the ACE2 expression,

increases the level of angiotensin II,

and exacerbates the lung injury.” The

“in vivo studies” they referred to here

(Kuba et al., 2005) had shown that

SARS coronavirus-induced lung injury

was primarily due to inhibition of

ACE2 by the SARS-CoV spike

protein, causing a large increase in angiotensin-II. Suzuki et al. (2021) went on to demonstrate

experimentally that the S1 component of the SARS-CoV-2 virus, at a low concentration of 130 pM,

activated the MEK/ERK/MAPK signaling pathway to promote cell growth. They speculated that

these effects would not be restricted to the lung vasculature. The signaling cascade triggered in the

heart vasculature would cause coronary artery disease, and activation in the brain could lead to

stroke. Systemic hypertension would also be predicted. They hypothesized that this ability of the

spike protein to promote pulmonary arterial hypertension could predispose patients who recover

Figure 2: A simple model for a process by which the spike

protein produced through the mRNA vaccines could induce a

pathological response distinct from the desirable induction of

antibodies to suppress viral entry. Redrawn with permission

from Suzuki and Gychka, 2021.

International Journal of Vaccine Theory, Practice, and Research 2(1), May 10, 2021 Page | 59

from SARS-CoV-2 to later develop right ventricular heart failure. Furthermore, they suggested that a

similar effect could happen in response to the mRNA vaccines, and they warned of potential longterm

consequences to both children and adults who received COVID-19 vaccines based on the

spike protein (Suzuki and Gychka, 2021).

An interesting study by Lei et. al. (2021) found that pseudovirus — spheres decorated with the

SARS-CoV-2 S1 protein but lacking any viral DNA in their core — caused inflammation and

damage in both the arteries and lungs of mice exposed intratracheally. They then exposed healthy

human endothelial cells to the same pseudovirus particles. Binding of these particles to endothelial

ACE2 receptors led to mitochondrial damage and fragmentation in those endothelial cells, leading to

the characteristic pathological changes in the associated tissue. This study makes it clear that spike

protein alone, unassociated with the rest of the viral genome, is sufficient to cause the endothelial

damage associated with COVID-19. The implications for vaccines intended to cause cells to

manufacture the spike protein are clear and are an obvious cause for concern.

Neurological symptoms associated with COVID-19, such as headache, nausea and dizziness,

encephalitis and fatal brain blood clots are all indicators of damaging viral effects on the brain.

Buzhdygan et al. (2020) proposed that primary human brain microvascular endothelial cells could

cause these symptoms. ACE2 is ubiquitously expressed in the endothelial cells in the brain

capillaries. ACE2 expression is upregulated in the brain vasculature in association with dementia and

hypertension, both of which are risk factors for bad outcomes from COVID-19. In an in vitro study

of the blood-brain barrier, the S1 component of the spike protein promoted loss of barrier integrity,

suggesting that the spike protein acting alone triggers a pro-inflammatory response in brain

endothelial cells, which could explain the neurological consequences of the disease (Buzhdygan et

al., 2020). The implications of this observation are disturbing because the mRNA vaccines induce

synthesis of the spike protein, which could theoretically act in a similar way to harm the brain.

The spike protein generated endogenously by the vaccine could also negatively impact the male

testes, as the ACE2 receptor is highly expressed in Leydig cells in the testes (Verma et al., 2020).

Several studies have now shown that the coronavirus spike protein is able to gain access to cells in

the testes via the ACE2 receptor, and disrupt male reproduction (Navarra et al., 2020; Wang and Xu,

2020). A paper involving postmortem examination of testicles of six male COVID-19 patients found

microscopic evidence of spike protein in interstitial cells in the testes of patients with damaged

testicles (Achua et al., 2021).

A Possible Link to Prion Diseases and Neurodegeneration

Prion diseases are a collection of neurodegenerative diseases that are induced through the misfolding

of important bodily proteins, which form toxic oligomers that eventually precipitate out as fibrils

causing widespread damage to neurons. Stanley Prusiner first coined the name `prion’ to describe

these misfolded proteins (Prusiner, 1982). The best-known prion disease is MADCOW disease

(bovine spongiform encephalopathy), which became an epidemic in European cattle beginning in

the 1980s. The CDC web site on prion diseases states that “prion diseases are usually rapidly

progressive and always fatal.” (Centers for Disease Control and Prevention, 2018). It is now

believed that many neurodegenerative diseases, including Alzheimer’s, Parkinson’s disease, and

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amyotrophic lateral sclerosis (ALS) may be prion diseases, and researchers have identified specific

proteinaceous infectious particles linked to these diseases (Weickenmeier et al., 2019).

Furthermore, researchers have identified a signature motif linked to susceptibility to misfolding into

toxic oligomers, called the glycine zipper motif. It is characterized by a pattern of two glycine

residues spaced by three intervening amino acids, represented as GxxxG. The bovine prion linked to

MADCOW has a spectacular sequence of ten GxxxGs in a row (see uniprot.org/uniprot/P10279).

More generally, the GxxxG motif is a common feature of transmembrane proteins, and the glycines

play an essential role in cross-linking α-helices in the protein (Mueller et al., 2014). Prion proteins

become toxic when the α-helices misfold as β-sheets, and the protein is then impaired in its ability to

enter the membrane (Prusiner, 1982). Glycines within the glycine zipper transmembrane motifs in

the amyloid-β precursor protein (APP) play a central role in the misfolding of amyloid- β linked to

Alzheimer’s disease (Decock et al., 2016). APP contains a total of four GxxxG motifs.

When considering that the SARS-CoV-2 spike protein is a transmembrane protein, and that it

contains five GxxxG motifs in its sequence (see uniprot.org/uniprot/P0DTC2), it becomes

extremely plausible that it could behave as a prion. One of the GxxxG sequences is present within

its membrane fusion domain. Recall that the mRNA vaccines are designed with an altered sequence

that replaces two adjacent amino acids in the fusion domain with a pair of prolines. This is done

intentionally in order to force the protein to remain in its open state and make it harder for it to fuse

with the membrane. This seems to us like a dangerous step towards misfolding potentially leading to

prion disease.

A paper published by J. Bart Classen (2021) proposed that the spike protein in the mRNA vaccines

could cause prion-like diseases, in part through its ability to bind to many known proteins and

induce their misfolding into potential prions. Idrees and Kumar (2021) have proposed that the spike

protein’s S1 component is prone to act as a functional amyloid and form toxic aggregates. These

authors wrote that S1 has the ability “to form amyloid and toxic aggregates that can act as seeds to

aggregate many of the misfolded brain proteins and can ultimately lead to neurodegeneration.”

According to Tetz and Tetz (2020), the form of the spike protein in SARS-CoV-2 has prion regions

that are not present in the spike proteins for other coronaviruses. While this was reported in a nonpeer-

reviewed article, the authors had published a previous paper in 2018 identifying prion-like

regions in multiple eukaryotic viruses, so they have considerable expertise in this area (Tetz and

Tetz, 2018).

A final point here relates to information about the Pfizer vaccine in particular. The European

Medicines Agency (EMA) Public Assessment Report is a document submitted to gain approval to

market the vaccine in Europe. It describes in detail a review of the manufacturing process as well as

a wide range of associated testing data. One concerning revelation is the presence of “fragmented

species” of RNA in the injection solution. These are RNA fragments resulting from early

termination of the process of transcription from the DNA template. These fragments, if translated

by the cell following injection, would generate incomplete spike proteins, again resulting in altered

and unpredictable three-dimensional structure and a physiological impact that is at best neutral and

at worst detrimental to cellular functioning. There were considerably more of these fragmented

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forms of RNA found in the commercially manufactured products than in the products used in

clinical trials. The latter were produced via a much more tightly controlled manufacturing process.

Pfizer claims the RNA fragments “likely… will not result in expressed proteins” due to their

assumed rapid degradation within the cell. No data was presented to rule out protein expression,

though, leaving the reviewers to comment, “These [fragmented RNA] forms are poorly

characterised, and the limited data provided for protein expression do not fully address the

uncertainties relating to the risk of translating proteins/peptides other than the intended spike

protein” (EMA 2020). To our knowledge no data has been forthcoming since that time.

While we are not asserting that non-spike proteins generated from fragmented RNA would be

misfolded or otherwise pathological, we believe they would at least contribute to the cellular stress

that promotes prion-associated conformational changes in the spike protein that is present.

1. Lessons from Parkinson’s Disease

Parkinson’s disease is a neurodegenerative disease associated with Lewy body deposits in the brain,

and the main protein found in these Lewy bodies is α-synuclein. That protein, α-Synuclein, is

certainly prion-like insofar as under certain conditions it aggregates into toxic soluble oligomers and

fibrils (Lema Tomé et al., 2013). Research has shown that misfolded α-synuclein can form first in the

gut and then travel from there to the brain along the vagus nerve, probably in the form of exosomes

released from dying cells where the misfolded protein originated (Kakarla et al., 2020; Steiner et al.,

2011). The cellular conditions that promote misfolding include both an acidic pH and high

expression of inflammatory cytokines. It is clear that the vagus nerve is critical for transmission of

misfolded proteins to the brain, because severance of the vagus nerve protects from Parkinson’s.

Vagus nerve atrophy in association with Parkinson’s disease provides further evidence of the

involvement of the vagus nerve in transport of misfolded α-synuclein oligomers from the gut to the

brain (Walter et al., 2018). Another pathway is through the olfactory nerve, and a loss of a sense of

smell is an early sign of Parkinson’s disease. Ominously, diminution or loss of the sense of smell is

also a common symptom of SARS-CoV-2 infection.

There are many parallels between α-synuclein and the spike protein, suggesting the possibility of

prion-like disease following vaccination. We have already shown that the mRNA in the vaccine ends

up in high concentrations in the liver and spleen, two organs that are well connected to the vagus

nerve. The cationic lipids in the vaccine create an acidic pH conducive to misfolding, and they also

induce a strong inflammatory response, another predisposing condition.

Germinal centers are structures within the spleen and other secondary lymphoid organs where

follicular dendritic cells present antigens to B cells, which in turn perfect their antibody response.

Researchers have shown that mRNA vaccines, in contrast with recombinant protein vaccines, elicit a

robust development of neutralizing antibodies at these germinal centers in the spleen (Lederer et al.,

2020). However, this also means that mRNA vaccines induce an ideal situation for prion formation

from the spike protein, and its transport via exosomes along the vagus nerve to the brain.

Studies have shown that prion spread from one animal to another first appears in the lymphoid

tissues, particularly the spleen. Differentiated follicular dendritic cells are central to the process, as

they accumulate misfolded prion proteins (Al-Dybiat et al., 2019). An inflammatory response

International Journal of Vaccine Theory, Practice, and Research 2(1), May 10, 2021 Page | 62

upregulates synthesis of α-synuclein in these dendritic cells, increasing the risk of prion formation.

Prions that accumulate in the cytoplasm are packaged up into lipid bodies that are released as

exosomes (Liu et al., 2017). These exosomes eventually travel to the brain, causing disease.

2. Vaccine Shedding

There has been considerable chatter on the Internet about the possibility of vaccinated people

causing disease in unvaccinated people in close proximity. While this may seem hard to believe,

there is a plausible process by which it could occur through the release of exosomes from dendritic

cells in the spleen containing misfolded spike proteins, in complex with other prion reconformed

proteins. These exosomes can travel to distant places. It is not impossible to imagine that they are

being released from the lungs and inhaled by a nearby person. Extracellular vesicles, including

exosomes, have been detected in sputum, mucus, epithelial lining fluid, and bronchoalveolar lavage

fluid in association with respiratory diseases (Lucchetti et al., 2021).

A Phase 1/2/3 study undertaken by BioNTech on the Pfizer mRNA vaccine implied in their study

protocol that they anticipated the possibility of secondary exposure to the vaccine (BioNTech,

2020). The protocol included the requirement that “exposure during pregnancy” should be reported

by the study participants. They then gave examples of “environmental exposure during pregnancy”

which included exposure “to the study intervention by inhalation or skin contact.” They even

suggested two levels of indirect exposure: “A male family member or healthcare provider who has

been exposed to the study intervention by inhalation or skin contact then exposes his female partner

prior to or around the time of conception.”

Emergence of Novel Variants of SARS-CoV-2

An interesting hypothesis has been proposed in a paper published in Nature, which described a case

of serious COVID-19 disease in a cancer patient who was taking immune-suppressing cancer

chemotherapy drugs (Kemp et al., 2021). The patient survived for 101 days after admission to the

hospital, finally succumbing in the battle against the virus. The patient constantly shed viruses over

the entire 101 days, and therefore he was moved to a negative-pressure high air-change infectious

disease isolation room, to prevent contagious spread.

During the course of the hospital stay, the patient was treated with Remdesivir and subsequently

with two rounds of antibody-containing plasma taken from individuals who had recovered from

COVID-19 (convalescent plasma). It was only after the plasma treatments that the virus began to

rapidly mutate, and a dominant new strain eventually emerged, verified from samples taken from the

nose and throat of the patient. An immune-compromised patient offers little support from cytotoxic

T cells to clear the virus.

An in vitro experiment demonstrated that this mutant strain had reduced sensitivity to multiple units

of convalescent plasma taken from several recovered patients. The authors proposed that the

administered antibodies had actually accelerated the mutation rate in the virus, because the patient

was unable to fully clear the virus due to their weak immune response. This allowed a “survival of

the fittest” program to set in, ultimately populating the patient’s body with a novel antibody-resistant

strain. Prolonged viral replication in this patient led to “viral immune escape,” and similar resistant

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strains could potentially spread very quickly within an exposed population (Kemp et al., 2021).

Indeed, a similar process might plausibly be at work to produce the highly contagious new strains

that are now appearing in the United Kingdom, South Africa and Brazil.

There are at least two concerns that we have regarding this experiment, in relation to the mRNA

vaccines. The first is that, via continued infection of immune-compromised patients, we can expect

continued emergence of more novel strains that are resistant to the antibodies induced by the

vaccine, such that the vaccine may quickly become obsolete, and there may well be demands for the

population to undergo another mass vaccination campaign. Already a published study by

researchers from Pfizer has shown that vaccine effectiveness is reduced for many of these variant

strains. The vaccine was only 2/3 as effective against the South African strain as against the original

strain (Liu et al., 2021).

The second more ominous consideration is to ponder what will happen with an immunecompromised

patient following vaccination. It is conceivable that they will respond to the vaccine by

producing antibodies, but those antibodies will be unable to contain the disease following exposure

to COVID-19 due to impaired function of cytotoxic T cells. This scenario is not much different

from the administration of convalescent plasma to immune-compromised patients, and so it might

engender the evolution of antibody-resistant strains in the same way, only on a much grander scale.

This possibility will surely be used to argue for repeated rounds of vaccines every few months, with

increasing numbers of viral variants coded into the vaccines. This is an arms race that we will

probably lose.

Potential for Permanent Incorporation of Spike Protein Gene into human DNA

It has been claimed that mRNA-based vaccines are safer than DNA-vectored vaccines that work by

incorporating the genetic code for the target antigenic protein into a DNA virus, because the RNA

cannot become inadvertently incorporated into the human genome. However, it is not at all clear

that this is true. The classic model of DNA → RNA → protein is now known to be false. It is now

indisputable that there is a large class of viruses called retroviruses that carry genes that reverse

transcribe RNA back into complementary DNA (cDNA). In 1975, Howard Temin, Renato

Dulbecco, and David Baltimore shared the Nobel Prize in Physiology or Medicine in 1975 for their

discovery of reverse transcriptase and its synthesis by retroviruses (such as human

immunodeficiency virus (HIV)) to derive DNA from RNA (Temin and Mizutani, 1970, Baltimore,


Much later, it was discovered that reverse transcriptase is not unique to retroviruses. More than a

third of the human genome is devoted to mysterious mobile DNA elements called SINEs and

LINEs (short and long interspersed nuclear elements, respectively). LINEs provide reverse

transcriptase capabilities to convert RNA into DNA, and SINEs provide support for integrating the

DNA into the genome. Thus, these elements provide the tools needed to convert RNA into DNA

and incorporate it into the genome so as to maintain the new gene through future generations

(Weiner, 2002).

SINEs and LINEs are members of a larger class of genetic elements called retrotransposons.

Retrotransposons can copy and paste their DNA to a new site in the genome via an RNA

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intermediate, while possibly introducing genetic alterations in the process (Pray, 2008).

Retrotransposons, also known as “jumping genes,” were first identified by the geneticist Barbara

McClintock of Cold Spring Harbor Laboratory in New York, over 50 years ago (McClintock, 1965).

Much later, in 1983, she was recognized with a Nobel prize for this work.

Remarkably, retrotransposons seem to be able to expand their domain from generation to

generation. LINEs and SINEs collaborate to invade new genomic sites through translation of their

DNA to RNA and back to a fresh copy of DNA, which is then inserted at an AT-rich region of the

genome. These LINEs and SINEs had long been considered to be “junk” DNA, an absurd idea that

has now been dispelled, as awareness of their critical functions has grown. In particular, it has now

become clear that they can also import RNA from an exogenous source into a mammalian host’s

DNA. Retroviral-like repeat elements found in the mouse genome called intracisternal A particles

(IAPs) have been shown to be capable of incorporating viral RNA into the mouse genome.

Recombination between an exogenous nonretroviral RNA virus and an IAP retrotansposon resulted

in reverse transcription of the viral RNA and integration into the host’s genome (Geuking et al.,


Furthermore, as we shall see later, the mRNA in the new SARS-CoV-2 vaccines could also get

passed on from generation to generation, with the help of LINEs expressed in sperm, via nonintegrated

cDNA encapsulated in plasmids. The implications of this predictable phenomenon are

unclear, but potentially far-reaching.

1. Exogenous and Endogenous Retroviruses

There is also a concern that the RNA in the mRNA vaccines could be transferred into the human

genome with assistance from retroviruses. Retroviruses are a class of viruses that maintain their

genomic information in the form of RNA, but that possess the enzymes needed to reverse

transcribe their RNA into DNA and insert it into a host genome. They then rely on existing natural

tools from the host to produce copies of the virus through translation of DNA back into RNA and

to produce the proteins that the viral RNA codes for and assemble them into a fresh viral particle

(Lesbats et al., 2016).

Human endogenous retroviruses (HERVs) are benign sections in the DNA of humans that closely

resemble retroviruses, and that are believed to have become permanent sequences in the human

genome through a process of integration from what was originally an exogenous retrovirus.

Endogenous retroviruses are abundant in all jawed vertebrates and are estimated to occupy 5-8% of

the human genome. The protein syncytin, which has become essential for placental fusion with the

uterine wall and for the fusion step between the sperm and the egg at fertilization, is a good example

of an endogenous retroviral protein. Syncytin is the envelope gene of a recently identified human

endogenous defective retrovirus, HERV-W (Mi et al., 2000). During gestation, the fetus expresses

high levels of another endogenous retrovirus, HERV-R, and it appears to protect the fetus from

immune attack from the mother (Luganini and Gribaudo, 2020). Endogenous retroviral elements

closely resemble retrotransposons. Their reverse transcriptase, when expressed, has the theoretical

capability to convert spike protein RNA from the mRNA vaccines into DNA.

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2. Permanent DNA integration of Exogenous Retrovirus Genes

Humans are colonized by a large collection of exogenous retroviruses that in many cases cause no

harm to the host, and may even be symbiotic (Luganini and Gribaudo, 2020). Exogenous viruses can

be converted to endogenous viruses (permanently incorporated into host DNA) in the laboratory, as

demonstrated by Rudolf Jaenisch (Jaenisch, 1976), who infected preimplantation mouse embryos

with the Moloney murine leukemia virus (M-MuLV). The mice generated from these infected

embryos developed leukemia, and the viral DNA was integrated into their germ line and transmitted

to their offspring. Besides the incorporation of viral DNA into the host genome, it was also shown

as early as 1980 that DNA plasmids could be microinjected into the nuclei of mouse embryos to

produce transgenic mice that breed true (Gordon et al., 1980). The plasmid DNA was incorporated

into the nuclear genome of the mice through existing natural processes, thus preserving the newly

acquired genetic information in the offspring’s genome. This discovery has been the basis for many

genetic engineering experiments on transgenic mice engineered to express newly acquired human

genes since then (Bouabe and Okkenhaug, 2013).

3. LINE-1 is Widely Expressed

LINEs alone make up over 20% of the human genome. The most common LINE is LINE-1, which

encodes a reverse transcriptase that regulates fundamental biological processes. LINE-1 is expressed

in many cell types, but at especially high levels in sperm. Sperm cells can be used as vectors of both

exogenous DNA and exogenous RNA molecules through sperm-mediated gene transfer assays.

Sperm can reverse transcribe exogenous RNA directly into cDNA and can deliver plasmids

packaging up this cDNA to the fertilized egg. These plasmids are able to propagate themselves

within the developing embryo and to populate many tissues in the fetus. In fact, they survive into

adulthood as extrachromosomal structures and are capable of being passed on to progeny. These

plasmids are transcriptionally competent, meaning that they can be used to synthesize proteins

encoded by the DNA they contain (Pittoggi et al., 2006).

In addition to sperm, embryos also express reverse transcriptase prior to implantation, and its

inhibition causes developmental arrest. LINE-1 is also expressed by cancer cells, and RNA

interference-mediated silencing of human LINE-1 induces differentiation in many cancer cell lines.

Reverse-transcriptase machinery is implicated in the genesis of new genetic information, both in

cancer cells and in germ cells. Many tumor tissues have been found to express high levels of LINE-

1, and to contain many extrachromosomal plasmids in their nucleus. Malignant gliomas are the

primary tumors of the central nervous system. It has been shown experimentally that these tumors

release exosomes containing DNA, RNA and proteins, that end up in the general circulation (Vaidya

and Sugaya, 2020). LINE-1 is also highly expressed in immune cells in several autoimmune diseases

such as systemic lupus erythematosus, Sjögrens and psoriasis (Zhang et al., 2020).

4. Integrating Spike Protein Gene into Human Genome

Remarkably, it has been demonstrated that neurons from the brain of Alzheimer’s patients harbor

multiple variants of the gene for amyloid precursor protein APP, incorporated into the genome,

which are created through a process called somatic gene recombination (SGR) (Kaeser et al., 2020).

SGR requires gene transcription, DNA strand-breaks, and reverse transcriptase activity, all of which

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may be promoted by well-known Alzheimer’s disease risk factors. The DNA coding for APP is

reverse transcribed into RNA and then transcribed back into DNA and incorporated into the

genome at a strand break site. Since RNA is more susceptible to mutations, the DNA in these

mosaic copies contains many mutant variants of the gene, so the cell becomes a mosaic, capable of

producing multiple variants of APP. Neurons from Alzheimer’s patients contained as many as 500

million base pairs of excess DNA in their chromosomes (Bushman et al., 2015).

Researchers from MIT and Harvard published a disturbing paper in 2021, where they provided

strong evidence that the SARS-CoV-2 RNA can be reverse transcribed into DNA and integrated

into human DNA (Zhang et al., 2021). They were led to investigate this idea after having observed

that many patients continue to test positive for COVID-19 after the virus has already been cleared

from their body. The authors found chimeric transcripts that contained viral DNA sequences fused

to cellular DNA sequences in patients who had recovered from COVID-19. Since COVID-19 often

induces a cytokine storm in severe cases, they confirmed the possibility of enhanced reverse

transcriptase activity through an in vitro study using cytokine-containing conditioned media in cell

cultures. They found a 2-3-fold upregulation of endogenous LINE-1 expression in response to

cytokines. The exogenous RNA from the virus incorporated into human DNA could produce

fragments of viral proteins indefinitely after the infection has been cleared, and this yields a falsepositive

on a PCR test.

5. Bovine Viral Diarrhea: A Disturbing Model

Bovine Viral Diarrhea (BVD) is an infectious viral disease that affects cattle throughout the world. It

is a member of the class of pestiviruses, which are small, spherical, single-stranded, enveloped RNA

viruses. The disease is associated with gastrointestinal, respiratory and reproductive diseases. A

unique characteristic of BVD is that the virus can cross the placenta of an infected pregnant dam.

This can result in the birth of a calf which carries intra-cellular viral particles which it mistakes as

`self.’ Its immune system refuses to recognize the virus as a foreign invasion, and, as a result, the calf

sheds the virus in large quantities throughout its life, potentially infecting the entire herd. It has

become a widespread practice to identify such carrier calves and cull them from the herd in an

attempt to curtail infection (Khodakaram-Tafti & Farjanikish, 2017).

It seems plausible that a dangerous situation may arise in the future where a woman receives an

mRNA vaccine for SARS-CoV-2 and then conceives a child shortly thereafter. The sperm would be

free to take up RNA-embedded liposomes from the vaccine and convert them to DNA using

LINE-1. They would then produce plasmids containing the code for the spike protein which would

be taken up by the fertilized egg through the process described above. The infant that is born is then

potentially unable to mount antibodies to the spike protein because their immune system considers

it to be `self.’ Should that infant get infected with SARS-CoV-2 at any time in its lifespan, its

immune system would not mount a defense against the virus, and the virus would presumably be

free to multiply in the infant’s body without restraint. The infant would logically become a superspreader

in such a situation. Admittedly, this is speculation at this time, but there is evidence from

what we know about retrotransposons, sperm, fertilization, the immune system and viruses, that

such a scenario cannot be ruled out. It has already been demonstrated in mouse experiments that the

genetic elements in DNA vector vaccines, which are essentially plasmids, can integrate into the host

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genome (Wang et al., 2004). In fact, such a process has been suggested as a basis for Lamarckian

evolution defined as the inheritance of acquired traits (Steele, 1980).

The realization that what was formerly called “junk DNA” is not junk, is just one of the results

coming out of the new philosophical paradigm in human language, biology and genetics that is based

on fractal genomics (Pellionisz, 2012) — a paradigm that Pellionisz has linked to the involvement of

“true narrative representations” (TNRs; Oller, 2010), realized as “iterations of a fractal template” in

the highly repetitive processes of normal development of the many branching structures of the

human body. These processes are numerous in the lungs, kidneys, veins and arteries, and most

importantly in the brain. The mRNA vaccines are an experimental gene therapy with the potential

to incorporate the code for the SARS-CoV-2 spike protein into human DNA. This DNA code

could instruct the synthesis of large numbers of copies of proteinaceous infectious particles, and this

has the potential to insert multiple false signals into the unfolding narrative, resulting in

unpredictable outcomes.


Experimental mRNA vaccines have been heralded as having the potential for great benefits, but they

also harbor the possibility of potentially tragic and even catastrophic unforeseen consequences. The

mRNA vaccines against SARS-CoV-2 have been implemented with great fanfare, but there are many

aspects of their widespread utilization that merit concern. We have reviewed some, but not all, of

those concerns here, and we want to emphasize that these concerns are potentially serious and might

not be evident for years or even transgenerationally. In order to adequately rule out the adverse

potentialities described in this paper, we recommend, at a minimum, that the following research and

surveillance practices be adopted:

• A national effort to collect detailed data on adverse events associated with the mRNA

vaccines with abundant funding allocation, tracked well beyond the first couple of weeks

after vaccination.

• Repeated autoantibody testing of the vaccine-recipient population. The autoantibodies tested

could be standardized and should be based upon previously documented antibodies and

autoantibodies potentially elicited by the spike protein. These include autoantibodies against

phospholipids, collagen, actin, thyroperoxidase (TPO), myelin basic protein, tissue

transglutaminase, and perhaps others.

• Immunological profiling related to cytokine balance and related biological effects. Tests

should include, at a minimum, IL-6, INF-α, D-dimer, fibrinogen, and C-reactive protein.

• Studies comparing populations who were vaccinated with the mRNA vaccines and those

who were not to confirm the expected decreased infection rate and milder symptoms of the

vaccinated group, while at the same time comparing the rates of various autoimmune

diseases and prion diseases in the same two populations.

• Studies to assess whether it is possible for an unvaccinated person to acquire vaccine-specific

forms of the spike proteins from a vaccinated person in close proximity.

• In vitro studies to assess whether the mRNA nanoparticles can be taken up by sperm and

converted into cDNA plasmids.

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• Animal studies to determine whether vaccination shortly before conception can result in

offspring carrying spike-protein-encoding plasmids in their tissues, possibly integrated into

their genome.

• In vitro studies aimed to better understand the toxicity of the spike protein to the brain,

heart, testes, etc.

Public policy around mass vaccination has generally proceeded on the assumption that the

risk/benefit ratio for the novel mRNA vaccines is a “slam dunk.” With the massive vaccination

campaign well under way in response to the declared international emergency of COVID-19, we

have rushed into vaccine experiments on a world-wide scale. At the very least, we should take

advantage of the data that are available from these experiments to learn more about this new and

previously untested technology. And, in the future, we urge governments to proceed with more

caution in the face of new biotechnologies.

Finally, as an obvious but tragically ignored suggestion, the government should also be encouraging

the population to take safe and affordable steps to boost their immune systems naturally, such as

getting out in the sunlight to raise vitamin D levels (Ali, 2020), and eating mainly organic whole

foods rather than chemical-laden processed foods (Rico-Campà et al., 2019). Also, eating foods that

are good sources of vitamin A, vitamin C and vitamin K2 should be encouraged, as deficiencies in

these vitamins are linked to bad outcomes from COVID-19 (Goddek, 2020; Sarohan, 2020).


This research was funded in part by Quanta Computers, Inc., Taiwan, under the auspices of the

Qmulus project.

Competing interests

The authors have no competing interests or conflicts to declare.


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