New Research by Frontiers In Immunology: Could Be Unwanted Genes In The Current COVID-19 Jabs

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Frontiers In Immunology Claims There Could Be Unwanted Genes In The Current COVID-19 Jabs.

The article by researchers from University of Cambridge-United Kingdom and the University of Ostrava-Czechia claim that there could be hidden or unwanted genes in the current COVID-19 jabs and certain adverse effects could actually be due to these genes! https://www.frontiersin.org/articles/10.3389/fimmu.2022.801915/full

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a positive-sense single-stranded RNA virus that was first described in late 2019 (1). SARS-CoV-2 is phylogenetically related to the causative agent of the 2002 SARS-CoV epidemic and causes many of the same symptoms, such as fever and myalgia (2).

Because of the high transmissibility of SARS-CoV-2 and rapid spreading throughout the world, by March 2020, the World Health Organization declared the global outbreak as the COVID-19 pandemic (3).

The health and economic-related losses accruing as a result of the pandemic led to the prioritization of prevention and treatment options with the quickest route to safe clinical application (4).

Although small molecule inhibitors and inactivated or live attenuated virus vaccine candidates have been used to successfully treat infection by pathogenic viruses, the pipelines to bring these products into clinical use can require significant time and resources with potentially low success rates (5, 6).

However, among novel vaccine delivery platforms developed in recent years, DNA and RNA vaccines have become of interest due to their potential to be inexpensively and quickly produced at a large scale (7). Only the nucleotide sequence of the selected antigenic protein is required to begin production, which can be derived from DNA/RNA sequencing of the virus. Thus, DNA/RNA vaccines have been suggested as prime candidates for mitigating COVID-19 transmission.

The SARS-CoV-2 genome codes for at least 30 proteins, three of which are exposed on the virion surface and can be recognized by the immune cell system (8–10). The spike protein is a large trimeric glycoprotein (1,273 amino acid long protomers) that protrudes from the virion surface to bind to cell surface receptors on host cells, such as angiotensin converting enzyme II (ACE2), in order to initiate viral entry (11).

The large surface area of the spike protein and its role in host cell entry make it attractive as a target for the immune system and clinical treatments, such as drugs and therapeutic antibodies (12). Of note, the spike protein is heavily glycosylated, which helps shield the virus from interactions with antibodies (13).

The region with the lowest degree of glycosylation is the receptor-binding domain, which binds to host cell surface proteins to initiate viral entry, and, as a result, is the most antigenic region of the spike protein (14). The other two proteins exposed on the virion surface, the envelope and membrane proteins, are also available for use as antigen targets; however, they are smaller in size and less accessible for protein-protein interactions than the spike protein. Because of the evidence indicating that spike is the most suitable antigenic target for SARS-CoV-2, it has been widely used in vaccine trials.

Numerous companies and academic institutions across the globe have developed or are currently developing DNA/RNA vaccines for the SARS-CoV-2 spike protein (15). Generally, in the case of DNA vaccines, the full-length SARS-CoV-2 spike protein DNA sequence is inserted into a plasmid, and additional technologies, such as electroporation, can assist in making transfection more efficient (16, 17).

The spike protein DNA transfected into the human cell can then be transcribed and translated to create the trimeric spike protein, which, then, moves to the endoplasmic reticulum and Golgi apparatus for post-translational modification (e.g. signal sequence cleavage, glycosylation) and continues through the secretory route to become anchored to the cell membrane for exposure to the immune system (18, 19)⁠.

The RNA-based vaccine formulations comprise lipid nanoparticles assembled around mRNA molecules coding for the full-length SARS-CoV-2 spike sequence (20). The transfected mRNA can be directly translated to make the spike protein. The BioNTech/Pfizer and Moderna mRNA vaccines, which have widely been approved by government agencies and administered in several countries, have reported approximately 50-70 and 70-90% effectiveness after 1 and 2 doses, respectively, against the wild-type and alpha variant (B.1.1.7) and 30-60 and 60-90% effectiveness, respectively, against the beta (B.1.351) and gamma (P.1) variants (21, 22).

However, additional variants of concern have been noted to provide either further partial or complete immune escape; thus, adapting the sequences may be required over time (23, 24). 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 (25). Further investigation into nucleic acid-based vaccine delivery platforms may improve effectiveness.

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 (26, 27).

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 (28–31). 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 (32–35).

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.

Conclusions

DNA/RNA vaccines have proven to be an effective way to develop vaccines quickly for emerging pathogens. However, with a new set of solutions, comes a new set of problems (80). Although the wild-type SARS-CoV-2 spike protein nucleotide sequence has been found to code for translated overlapping genes, ORF detection predictions on the sequences of two mRNA vaccines reveal that codon optimization has the potential to disrupt non-specific translation.

Additional overlapping ORFs can arise during codon optimization; thus, the final sequences should nevertheless be scrutinized for their protein-coding potential. In the case of DNA vaccines and viral vectors, the negative-sense strand should also be checked for its protein-coding potential.

Additionally, as variants of concern become known and vaccines are altered to include them, the spontaneous generation of ORFs should be re-assessed. Many precautionary steps have been taken to ensure the safety and efficacy of the mRNA vaccines, including nucleoside modification to reduce inflammatory responses and 5’-capping and polyadenylation tail length optimization to increase mRNA stability and translation (20).

Thus, the inclusion of additional steps to ensure that vaccine sequences code solely for the intended protein may also lead to better health and safety outcomes. Measures to check for other adverse effects on host cells, such as those resulting from potential interactions of vaccine nucleotide sequences with host RNAs or proteins, or the host microbiome may be increase efficacy and safety as well (81)⁠. More in-depth investigation of these delivery methods may reveal aspects that should be further refined to safeguard against unintended side effects.

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