Covid mRNA - Vaccine or Gene Therapy?

How should they be regulated?

From the very beginning of the vaccine rollout, the speed of this new technology has led to questions and concerns, especially regarding the classification of mRNA vaccines. Are they traditional vaccines or a form of gene therapy? This question is not merely academic but has implications for how these vaccines are regulated and perceived by the public. If they are considered gene therapy, would the general public have rolled up their sleeves so quickly and easily?

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In a new article titled "mRNA: Vaccine or Gene Therapy? The Safety Regulatory Issues," published in the International Journal of Molecular Sciences, author Helene Banoun delves into these complex issues.

COVID-19 vaccines were developed and approved rapidly in response to the urgency created by the pandemic. No specific regulations existed at the time they were marketed. The regulatory agencies therefore adapted them as a matter of urgency. Now that the pandemic emergency has passed, it is time to consider the safety issues associated with this rapid approval.

Unless you have been living under a rock for the last few years, you will know that vaccines traditionally use harmless parts of a virus to stimulate our immune response. Gene therapy, however, alters genes within cells to treat diseases. mRNA vaccines, like Pfizer-BioNTech and Moderna's COVID-19 vaccines, use a new approach. They contain mRNA, a genetic material that instructs our cells to produce spike protein and thereby triggering an immune response. This is meant to prepare our bodies to fight the actual virus.

As mentioned above, gene therapy is a medical field that alters genes within an individual's cells to treat or prevent disease. It can involve replacing a disease-causing gene with a healthy one, inactivating a disease-causing gene or introducing a new or modified gene to help treat a disease.

Banoun explains in her article that there are key differences between mRNA vaccines and gene therapy. One of the most important differences, according to her, is that mRNA vaccines do not alter our DNA. The mRNA from the vaccine does its job in the outer part of the cell, and then it's destroyed by the cell. This is a key distinction from gene therapy, which involves making changes to an individual's genes.

So are these novel Covid mRNA shots vaccines or gene therapies?

The purpose of both traditional and mRNA vaccines is to teach our immune system how to fight off the virus if we are exposed to it in the future. This aligns with the definition of a vaccine, which is a substance that stimulates an immune response, protecting us against future infection with the virus.

On the other hand, one can argue that mRNA vaccines are more like gene therapy. Gene therapy involves altering the genes inside your body's cells in an effort to treat or stop disease. mRNA vaccines do alter the genetic instructions inside our cells, but only to produce a piece of the virus, not to change our DNA or cure a genetic disease.

Currently, mRNA vaccines are classified differently depending on their target and how they are obtained. For instance, mRNA vaccines aimed at combating infectious diseases are not classified as gene therapy products. However, mRNA vaccines developed for the treatment of cancers are classified as gene therapy medicinal products. This classification determines the controls and studies that must be carried out to obtain marketing authorizations.

The role of regulatory agencies is to ensure the safety and efficacy of medicines. The COVID-19 pandemic emergency has accelerated the timetable for the production and clinical use of COVID-19 vaccines; it is, therefore, possible that certain safety aspects have not been fully addressed. It is, therefore, important to take these aspects into account in the future, so as not to undermine public confidence in vaccines in general.

The article also discusses reports of adverse events following mRNA vaccination, such as myocarditis and certain types of lymphoma.

Furthermore, the detection of vaccine mRNA in blood post-vaccination is another safety concern. This has raised questions about the potential long-term effects of these vaccines, especially since the long-term effects of mRNA vaccines are still not fully understood.

Another issue discussed is the potential for reverse-transcribed SARS-CoV-2 RNA to integrate into the genome of human cells. Some research has suggested that this is possible, although the implications of this are still not fully understood. This has led to debates about whether mRNA vaccines should be classified as gene therapy, which has different regulatory requirements.

The mode of action of COVID-19 mRNA vaccines should classify them as gene therapy products (GTPs), but they have been excluded by regulatory agencies. Some of the tests they have undergone as vaccines have produced non-compliant results in terms of purity, quality and batch homogeneity.

The article goes on to discuss the regulatory classification of mRNA vaccines, which, despite functioning similarly to gene therapy products (GTPs), are not subjected to GTP regulations. This discrepancy, which lacks scientific or ethical justification, has led to inconsistencies in regulations. For instance, European and French regulations stipulate that a vaccine must contain an antigen, which is not the case for mRNA vaccines. These vaccines, which could be considered "pro-vaccines" or "pro-drugs," prompt the vaccinee to produce the antigen. The author suggests that special regulations should be drawn up for this type of product, emphasizing controls on potency, i.e., the quality, quantity, duration, and sites of expression of the antigen of interest, as well as the toxicity of this antigen.

Banoun highlights the need for pharmacokinetic studies for mRNA vaccines, which are considered new formulations. Such studies would detect the wide distribution and persistence of mRNA and its product, the spike protein, in the bodies of vaccinees, the passage of mRNA in breast milk, and the possible passage through the placenta of vaccinated mothers. She argues that due to the wide and persistent biodistribution of mRNA vaccines, essential tests required for GTPs should have been carried out regarding the risk of genotoxicity, genome integration, germ-line transmission, insertional mutagenesis, tumorigenicity, embryo/fetal and perinatal toxicity, long-term expression, repeated toxicity, and excretion in the environment.

Some of the tests they have undergone as vaccines have produced non-compliant results in terms of purity, quality and batch homogeneity. The wide and persistent biodistribution of mRNAs and their protein products, incompletely studied due to their classification as vaccines, raises safety issues. Post-marketing studies have shown that mRNA passes into breast milk and could have adverse effects on breast-fed babies. Long-term expression, integration into the genome, transmission to the germline, passage into sperm, embryo/fetal and perinatal toxicity, genotoxicity and tumorigenicity should be studied in light of the adverse events reported in pharmacovigilance databases. The potential horizontal transmission (i.e., shedding) should also have been assessed. In-depth vaccinovigilance should be carried out. We would expect these controls to be required for future mRNA vaccines developed outside the context of a pandemic.

Banoun argues that the distinctions highlighted above are not sufficient to justify the different regulatory treatment of mRNA vaccines and gene therapy products. She suggests that the mode of action of mRNA vaccines should classify them as gene therapy products, and that they should be subject to the same regulations and controls as other gene therapy products.