The mRNA Lipid Nanoparticle COVID-19 Vaccines and the Toxicity
A brief view of recent adverse events of COVID-19 mRNA vaccines.
Lipid nanoparticles (LNPs) are on the stage of social medias' conversations since the vaccine for COVID-19 were rolled out by the end of 2020. LNP is used as carrier for the SARS-COV-2 mRNA Spike proteins. Scientific journals reported the efficacies and good titers numbers of the trials phases of the vaccines. The mRNAs of Spike (S) proteins of SARS-CoV-2 are packed inside the LNPs and intramuscularly transferred into the body. Spike proteins are used by the virus to docking to our cells. The idea is to let our antibodies block the binding of S proteins and our cell.
I have described PEG and anaphylaxis, the side effect of PEG in my June article about nanocarriers. PEG is also used in COVID-19 mRNA vaccine.
The S proteins are toxic, mostly is the Lipo polysaccharide (LPS) part. LPS has many disease and toxicity effects, one of them is LPS can cause prions disease. A paper reported a minimal version of LPS containing a portion of the polysaccharide and a portion of the lipid component is sufficient for PrP conversion1. LPS also can cause gastrointestinal diseases and autoimmune diseases such as multiple sclerosis and Guillain-Barre Syndrome. LPS can work through the mimicry mechanism with our own proteins2.
Recent reports showed adverse events of COVID-19 vaccines, especially the mRNA vaccines and one of them is Guillain-Barre syndrome (GBS). GBS was found in an 82-year-old highly functional female at baseline without significant comorbidities after she had her first Pfizer mRNA COVID-19 vaccine vaccination. Though the number is just for this case, we don't know for sure for the unreported cases3. Multiple sclerosis (MS) after mRNA vaccines was found in a 28-year-old woman. She developed the first clinical manifestation of relapsing MS after vaccination with the Pfizer mRNA COVID-19 vaccine. The symptoms came six days after the first dose of the vaccination4.
Absorption of nanoparticles (LNP) is also possible when the nanomaterial first interacts with proteins or cells and might affect organs such as liver, brain, spleen, blood, kidney, heart, colon, bone, etc., and cause deleterious cytotoxic effects leading to deformation and inhibition of cell growth in humans and animals. The lipid that is used in LNP for the COVID-19 mRNA vaccines, are cationic lipid. This lipid may have interaction with serum proteins, lipoproteins and extracellular matrix in our body leading to aggregation or release of agents that are loaded before reaching the target cells thus, systemic toxicity presents. It may become surfactants for our cells that will lower the surface tension and lead to membrane solubilization, poration, and lysis. Cationic lipid can cause liver damage, cellular influx, lung inflammation through reactive oxygen species (ROS) induction, and macrophages mediated toxicity less than 3 hours after the lipid is in our body5.
Cationic nanocarriers are reported to induce cell necrosis. Mitochondrial DNA (mtDNA) from the injured cell may cause in the inflammatory toxicity of the nanocarrier, which has largely limited its clinical application. Partial blocking of the surface charge of cationic nanocarriers, such as Hyaluronan (HA), will lower it's toxicity6.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5161299/
https://en.m.wikipedia.org/wiki/Lipopolysaccharide
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7978140/
https://pubmed.ncbi.nlm.nih.gov/34115170/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3245366/#!po=13.0952
https://pubs.acs.org/doi/10.1021/acsami.8b12393