Page 9 - Dr Stephanie Seneff - Reviewing Some Possible Unintended Consequences of the mRNA Vaccines Against COVID - 19

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.,
2021).

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
International Journal of Vaccine Theory, Practice, and Research 2(1), May 10, 2021 Page | 397