Transfection Not Vaccination

Looks like we’ve confused some terminology in the last year when understanding the mechanisms of mRNA in translation as opposed to traditional vaccination strategies. Let me break it down.

Traditionally, scientist combine part of a pathogen with some other agents to elicit an immune response. This fragment of the causative organism should be recognized as foreign by the immune system. The immune system then flags it, memorizes its structure, and destroys it. At the next exposure, the immune system attacks the pathogen before the onset of illness. Illness averted. Novel theory, should everything go as planned.

Moving on, now, to transfection which is actually quite different. It basically makes your body produce the part of the pathogen by inserting a genetic code and using your body to do the creating… and destruction. I’m sure you can see what part of that can be problematic when it comes to the immune system flagging something your body is manufacturing as foreign…?

If you want a visual of this process, Khan Academy is always such a great reference.

mRNA is like a recipe
ribosomes are the kitchen/oven
tRNA is the baker adding ingredients
protein is the cake
Aaand, cake is life… amiright?
Well, proteins are the BUILDING BLOCKS OF LIFE… so they’re kind of a big deal.

This whole process is known as transfection when done with a foreign particles.

So, this time, scientists picked a part of the pathogen, the Spike glycoprotein, for your body to create. Then *hopefully* your immune system destroys (while sparing your self cells) and attacks it at next exposure before onset of illness. Illness averted…? Except this technology has never been used in humans and has gone horribly wrong in animal trials during challenge phases:

*A Double-Inactivated Severe Acute Respiratory Syndrome Coronavirus Vaccine Provides Incomplete Protection in Mice and Induces Increased Eosinophilic Proinflammatory Pulmonary Response upon Challenge (https://doi.org/10.1128/JVI.06048-11)
*Cellular Immune Responses to Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) Infection in Senescent BALB/c Mice: CD4+ T Cells Are Important in Control of SARS-CoV Infection (https://doi.org/10.1128/JVI.01281-09)
*Evasion by Stealth: Inefficient Immune Activation Underlies Poor T Cell Response and Severe Disease in SARS-CoV-Infected Mice (https://doi.org/10.1371/journal.ppat.1000636)
*Immunization with inactivated Middle East Respiratory Syndrome coronavirus vaccine leads to lung immunopathology on challenge with live virus (https://doi.org/10.1080/21645515.2016.1177688)
*Immunization with Modified Vaccinia Virus Ankara-Based Recombinant Vaccine against Severe Acute Respiratory Syndrome Is Associated with Enhanced Hepatitis in Ferrets (https://doi.org/10.1128/JVI.78.22.12672-12676.2004)
*Immunization with SARS Coronavirus Vaccines Leads to Pulmonary Immunopathology on Challenge with the SARS Virus (https://doi.org/10.1371/journal.pone.0035421)
*Pathogenic priming likely contributes to serious and critical illness and mortality in COVID-19 via autoimmunity (https://doi.org/10.1016/j.jtauto.2020.100051)
*Structural Basis of SARS-CoV-2 and SARS-CoV Antibody Interactions (https://doi.org/10.1016/j.it.2020.09.004)
*Two Different Antibody-Dependent Enhancement (ADE) Risks for SARS-CoV-2 Antibodies (https://doi.org/10.3389/fimmu.2021.640093)
*Vaccine Efficacy in Senescent Mice Challenged with Recombinant SARS-CoV Bearing Epidemic and Zoonotic Spike Variants (https://doi.org/10.1371/journal.pmed.0040080)

Everyone touts how the vaccine stays in your injected muscle and “does not move” about the cabin… what if its ingredients had some questionable qualities that allow it to do just that? You be the judge…

https://www.fda.gov/media/144413/download
https://guardianconsulting.com/wp-content/uploads/2020/12/Moderna-COVID-19-vaccine_FULL_EUA.pdf
https://www.janssenlabels.com/emergency-use-authorization/Janssen+COVID-19+Vaccine-HCP-fact-sheet.pdf

So what are these lipid nanoparticles?
In short, most of the literature is focused on how a lipid nanoparticle can assist a product to pass the blood brain barrier. That’s a little odd. Cell membranes contain lipids so these lipid nanoparticles allow attachment of these mRNA products so that it may enter the cytosol for action. What purpose does the mRNA have specific to the brain? Your guess is as good as mine, but make your own conclusions for the research surrounding lipid nanoparticles (that are in both the Moderna and Pfizer concoctions).

Basophil reactivity to BNT162b2 is mediated by PEGylated lipid nanoparticles in patietnts with PEG allergy (https://doi.org/10.1016/j.jaci.2021.04.032)
Design of lipid nanoparticles for in vitro and in vivo delivery of plasmid DNA (http://doi.org/10.1016/j.nano.2016.12.014)
Development and screening of brain-targeted lipid-based nanoparticles with enhanced cell penetration and gene delivery properties (https://doi.org/10.2147/IJN.S215941)
Enhanced target cell specificity and uptake of lipid nanoparticles using RNA aptamers and peptides (https://doi.org/10.3762/bjoc.17.75)
Functionalized lipid nanoparticles for subcutaneous administration of mRNA to achieve systemic exposures of a therapeutic protein (https://doi.org/10.1016/j.omtn.2021.03.008)
Future considerations for the mRNA-lipid nanoparticle vaccine platform (https://doi.org/10.1016/j.coviro.2021.03.008)
Immune response scenario and vaccine development for SARS-CoV-2 infection (https://doi.org/10.1016/j.intimp.2021.107439)
Intracellular Routing and Recognition of Lipid-Based mRNA Nanoparticles (https://doi.org/10.3390/pharmaceutics13070945)
Lipid Nanoparticles as Carriers for Bioactive Delivery (https://doi.org/10.3389/fchem.2021.580118)
Lipid Nanoparticles: A Novel Approach for Brain Targeting (https://doi.org/10.2174/2211738506666180611100416)
Lipid Nanoparticle-Mediated Delivery of mRNA Therapeutics and Vaccines (https://doi.org/10.1016/j.molmed.2021.03.003)
Potential SARS-CoV-2 vaccines: Concept, progress, and challenges (https://doi.org/10.1016/j.intimp.2021.107622)
Recent advances in drug delivery applications of cubosomes, hexosomes, and solid lipid nanoparticles (https://doi.org/10.1016/j.apsb.2021.02.013)
SARS-CoV-2 RNA reverse-transcribed and integrated into the human genome (https://doi.org/10.1101/2020.12.12.422516)

Janssen is not spared as it contains polysorbate-80 which does not have the most reassuring SDS. Again, you can decide for yourself…

A Novel Formulation Based on 2,3-Di(tetradecyloxy)propan-1-amine Cationic Lipid Combined with Polysorbate 80 for Efficient Gene Delivery to the Retina (https://doi.org/10.1007/s11095-013-1271-5)
Biologic excipients: Importance of clinical awareness of inactive ingredients (https://doi.org/10.1371/journal.pone.0235076)
Cationic and anionic unloaded polymeric nanocapsules: Toxicological evaluation in rats shows low toxicity (https://doi.org/10.1016/j.biopha.2019.109014)
Complement activation associated with polysorbate 80 in beagle dogs (https://doi.org/10.1016/j.intimp.2012.10.021)
Considerations for the Use of Polysorbates in Biopharmaceuticals (https://doi.org/10.1007/s11095-018-2430-5)
COVID-19 Vaccine-associated Anaphylaxis and Allergic Reactions: Consensus Statements of the KAAACI Urticaria/Angioedema/Anaphylaxis Working Group (https://doi.org/10.4168/aair.2021.13.4.526)
Non‐IgE‐mediated hypersensitivity induced by multivitamins containing Tween‐80 (https://doi.org/10.1111/1440-1681.13089)
Reducing or Eliminating Polysorbate Induced Anaphylaxis and Unwanted Immunogenicity in Biotherapeutics (https://www.neurelis.com/sites/default/files/pdf/Reducing%20or%20Eliminating%20Polysorbate%20Induced%20Anaphylaxis%20and%20Unwanted%20Immunogenicity%20in%20Biotherapeutics.pdf)
Successful SARS-CoV-2 vaccine allergy risk-management: The experience of a large Italian University Hospital (https://doi.org/10.1016/j.waojou.2021.100541)
Surface-modified polycaprolactone nanoparticles for the brain-targeted delivery of nevirapine (https://doi.org/10.1007/s11051-020-04831-9)

At the very least, these investigational products are just that… under investigation. And, no, nobody should be allowed to coerce you with free food, cars, money, lottery, employment retention, or otherwise to be part of this gene therapy exercise and be totally free from liability. We have be here before and it was not pretty. More on that to come.

Shalom, light, and love…

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