Page 8 - Dr Stephanie Seneff - Reviewing Some Possible Unintended Consequences of the mRNA Vaccines Against COVID - 19
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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 GC-
               poor 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
               protein.
               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
               protein.


                   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
                              International Journal of Vaccine Theory, Practice, and Research 2(1), May 10, 2021 Page | 396
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