Apparent Cytotoxicity and Intrinsic Cytotoxicity of Lipid Nanomaterials Contained in a COVID-19 mRNA Vaccine

Abstract

The medicinal preparation called Comirnaty by Pfizer-BioNTech is an aqueous dispersion of lipid nanomaterials, intended to constitute, after thawing and dilution, the finished product for intramuscular injection. In the present study, we examine some evident chemical-physical criticalities of the preparation, particularly regarding the apparent and the intrinsic pKa (acid dissociation constant) of its main excipient, the ionizable cationic lipid ALC-0315. The very high value of its intrinsic pKa causes, after internalization and endosomal escape of LNPs, a sudden increase of its cationic charge concentration and consequently the formation of pro-inflammatory cytokines and ROS (reactive oxygen species), that can disrupt the mitochondrial membrane and release its content, cause RNA mistranslation, polymerization of proteins and DNA, DNA mutations, destruction of the nuclear membrane and consequent release of its content. Additionally, the apparently low pKa value (6.09) of ALC-0315 associated with other lipids in the LNP, is not suitable for intramuscular application. Its value is too low to enable a proper transfection of host cells, despite what is stated by EMA (European Medicines Agency) in its Assessment report dated 19 February 2021, in flagrant contradiction with the same bibliographic source therein cited. Furthermore, the exceptional penetrability, mobility, chemical reactivity and systemic accumulation of uncontrollable cationic lipid nanoparticles, with high cytotoxicity levels, shed in unpredictable biological locations, even far from the site of inoculation, are all factors that can lead to an unprecedented medical disaster. Meanwhile, further immediate studies and verifications are recommended, taking into consideration, in accordance with the precautionary principle, the immediate suspension of vaccinations with the COVID-19 mRNA- LNP-based vaccines.