Understanding the Pharmacology of COVID-19 mRNA Vaccines: Playing Dice with the Spike?

"1. Introduction

In most Western countries, the mass Coronavirus disease-19 (COVID-19) vaccination campaigns, which have been ongoing since the end of 2020, are based on two mRNA vaccines against SARS-CoV-2 (BioNTech–Pfizer BNT162b2 and Moderna mRNA-1273). Both products contain mRNAs encoding the SARS-CoV-2 spike (S) protein, which is essential in the binding of the virus to the host cells expressing its receptor angiotensin-converting enzyme 2 (ACE2). These products were presented from the outset as intrinsically safe, since it was believed that, similar to conventional vaccines, after intramuscular injection, most of the dose would remain in the muscle and the rest would drain through the lymphatic system, being eventually captured by antigen-presenting cells and B cells and undergoing complete elimination in a few tens of hours at the most. On this basis, the public was explicitly reassured by influential blogs as well as by academic institutional web pages that these products were not expected to exhibit any relevant systemic disposition and that the resulting S protein would remain attached to the surface of the cells and would not be released in the bloodstream and tissues to encounter ACE2 receptors and eventually induce organ damage. Step by step, however, it became clear that this was not the case...

2. Evidence for Systemic Biodistribution of COVID-19-Vaccine-Induced S Protein in Vaccinated Subjects

... Taken as a whole, evidence strongly supports the possible link between inappropriate expression of S protein in sensitive tissues and subsequent tissue damage.

3. Adverse Effects Following COVID-19 Vaccination: Too Much S Protein, for Too Long and/or in the WRONG Place?

... [A] major explanation of adverse effects following COVID-19 vaccination could well be that mRNA vaccines induce in selected individuals excessive production of S protein, for too long and/or in inappropriate tissues and organs, and this occurrence is at present unpredictable, since systemic biodistribution and disposition of the COVID-19 mRNA vaccine has so far never been considered an issue, and as a consequence it has never been studied as it would have actually deserved...

4. COVID-19 mRNA Vaccines: Pharmaceutical Drugs Rather than Conventional Vaccines

... In summary, both the SARS-CoV-2 S protein mRNA and the S protein itself exhibit a complex pharmacological profile with potential toxicological issues. None of these issues, however, were taken into consideration in the studies that led to the marketing authorization, precisely because, first of all, from a regulatory point of view, these products were treated as conventional vaccines.

6. Conclusions

Since translation of the mRNA occurs potentially and—most importantly—unpredictably in any tissues and organs, and it can be easily hypothesized that inappropriate production in vulnerable tissues may represent a major risk factor for local tissue damage, leading to myocarditis, central and peripheral neuropathies, vasculopathies, myopathies, endocrinopathies and other disease, depending on the location and amount of S protein expression (or of local distribution from general circulation)...

Unfortunately, at present we have almost none of the information necessary to address and manage all these aspects, and to use COVID-19 mRNA vaccines in a conscious, targeted and rational way."