Abstract:

The advent of the mRNA-based COVID-19 vaccines heralds a transformation in the world of immunization. The use of mRNA to stimulate antigenic foreign protein synthesis by host cells, which triggers an immune reaction that repels future true infection, has been theorized for decades. The COVID-19 vaccines represent the first mass deployment of this genetic technology. Using modified mRNA sequences for the COVID-19 spike protein, delivered in a lipid nanoparticle vehicle, injection with the COVID-19 vaccine is intended to recruit host cells that manufacture the spike protein and generate an immune response that protects against future infection.

There are numerous potential advantages to an mRNA vaccine platform, including scalability and time to development. What is not well studied, however, is the potential for derangements in genetic processing, protein synthesis, and the production of off-target proteins as a result of frameshifting. While these are considerations in all mRNA vaccine recipients, such concerns may be of even more significance in individuals with aneuploidies, where there are well-established alterations in genetic metabolic processes and derangements in responses to oxidative stress. While there have been adverse effects, such as myocarditis, identified after largescale vaccine rollout, patients with aneuploidy are possibly a subgroup at much greater risk for adverse events related to COVID-19 mRNA vaccines.