Are There Hidden Genes in DNA/RNA Vaccines?

"Abstract

... Vaccination campaigns have reported high vaccination rates and protection, but numerous unintended effects, ranging from muscle pain to death, have led to concerns about the safety of RNA/DNA vaccines. In parallel to these studies, several open reading frames (ORFs) have been found to be overlapping SARS-CoV-2 accessory genes, two of which, ORF2b and ORF-Sh, overlap the spike protein sequence. Thus, the presence of these, and potentially other ORFs on SARS-CoV-2 DNA/RNA vaccines, could lead to the translation of undesired proteins during vaccination. Herein, we discuss the translation of overlapping genes in connection with DNA/RNA vaccines. Two mRNA vaccine spike protein sequences, which have been made publicly-available, were compared to the wild-type sequence in order to uncover possible differences in putative overlapping ORFs. Notably, the Moderna mRNA-1273 vaccine sequence is predicted to contain no frameshifted ORFs on the positive sense strand, which highlights the utility of codon optimization in DNA/RNA vaccine design to remove undesired overlapping ORFs. Since little information is available on ORF2b or ORF-Sh, we use structural bioinformatics techniques to investigate the structure-function relationship of these proteins. The presence of putative ORFs on DNA/RNA vaccine candidates implies that overlapping genes may contribute to the translation of smaller peptides, potentially leading to unintended clinical outcomes, and that the protein-coding potential of DNA/RNA vaccines should be rigorously examined prior to administration.

Introduction

... Prior to COVID-19, no DNA/RNA vaccines had been approved for human use, but, in August 2021, BioNTech and Pfizer received FDA approval for use of their mRNA vaccine.

Although SARS-CoV-2 DNA/RNA vaccines have been subjected to health and safety testing prior to bulk dissemination, a diverse assortment of both systemic and local (near injection site) side effects, ranging from mild to severe, following vaccination have been described. Symptoms resembling that of viral infection (e.g. headache and myalgia), life-threatening conditions (e.g. myocardial injury and thrombosis), and mortalities have been reported in relation to vaccination. Although some side effects may stem from the delivery modalities, several studies have indicated that the spike protein alone causes adverse effects on host tissues, such as blood brain barrier disruption, neuron fusion, inflammation, and cell senescence. Although it is difficult to detect the origin of side effects in vaccinated individuals, more investigation on the cellular effects of mRNA vaccines or the expressed protein antigen are warranted to create safer vaccines."