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Let's do a deep dive on coronavirus DNA vaccines. This long thread looks closely at DNA vaccines, and will specifically address their potential to edit the human genome. If you make it through, you will be stunned at what you learn, as things are never as they seem.
There are no less than 8 DNA vaccines in development for Coronavirus, including:
ZyCoV-D by Zydus Cadila
AG0301-COVID19 by AnGes Inc
GX-19 by Genexine
INO-4800 by Inovio
bacTRL-Spike by Symvivo
LineaDNA by Takis Biotech
2 more by ImmunityBio and Sanofi https://www.raps.org/news-and-articles/news-articles/2020/3/covid-19-vaccine-tracker
ZyCoV-D by Zydus Cadila
AG0301-COVID19 by AnGes Inc
GX-19 by Genexine
INO-4800 by Inovio
bacTRL-Spike by Symvivo
LineaDNA by Takis Biotech
2 more by ImmunityBio and Sanofi https://www.raps.org/news-and-articles/news-articles/2020/3/covid-19-vaccine-tracker
DNA vaccines have been used in numerous clinical trails back in the late 90's but have never been approved for use among the general public. They have never been perfected, and should be considered experimental. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6274812/
DNA vaccines seemed appealing to scientists because of their potential ability to illicit MHC class 1 processed cytotoxic lymphocyte responses, and targeted T-helper, as well as antibody responses. https://pubmed.ncbi.nlm.nih.gov/12653868/
Do not confuse the DNA vaccine with the mRNA vaccine (e.g. Moderna 1273). They function very differently. The goal of both is to produce surface proteins on the human cell, but the DNA vaccine adds an extra step. It relies on DNA to transfect the cell nucleus. The mRNA does not.
One may suspect that adding foreign DNA to the nucleus could be risky because it may recombine with your own endogenous DNA. Although the vaccine is not intended to work this way, integration has always been widely acknowledged as a potential serious risk factor.
Let's look at an example of a recent study that attempts to minimize the risk of accidental DNA integration. https://www.mdpi.com/2076-393X/7/2/37/htm
The study states, DNA vaccines did not need to be evaluated by NIH prior to trails, unlike vectors for gene therapy, but that safety studies were used to evaluate possibility of DNA integration into the host genome. As a result, little concern now exists regarding integration.
It goes onto say that risk of integration is no longer a significant concern for DNA vaccines, and that from a regulatory perspective, the vaccine is not considered a gene therapy product. But things are not always as they appear, so let's go deeper.
An earlier 2016 study that actually revolves around a DNA vaccine for MERS coronavirus might provide more insight into the so called "safety studies" that allegedly took place and justify "little concern" for risk of DNA integration into the host. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5233508/
We learn that early preclinical studies in animal models raised potential safety concerns that were later adopted by the FDA as guidance for industry when addressing immunogenicity and safety of a DNA delivery platform.
Some of the safety concerns raised include: garnering an understanding of the bio-distribution, persistence, and DNA integration profiles potentially associated with the delivery of any DNA molecule into the nucleus of a mammalian cell.
A further concern is that a vaccine might cause insertional mutagenesis through the activation of oncogenes or the inactivation of tumor suppressor genes.
In addition, a plasmid DNA vaccine could, in theory, result in chromosomal instability through the induction of chromosomal breaks or rearrangements. However, none of these concerns have been witnessed in the preclinical or clinical evaluation of DNA products.
Due to the accumulated success of multiple phase I clinical studies over the last decade, the FDA guidelines have become more relaxed over time.
Caveats in the FDA guidelines include waivers of bio-distribution studies if the “novel gene is inserted into a plasmid vector previously documented to have an acceptable bio-distribution / integration profile”.
Additionally, that “integration studies are warranted only when DNA plasmid persists in any tissue of any animal at levels exceeding 30,000 copies per µg of host DNA by study termination”.
Curiously, the preclinical research studies that established the precedent for assessing bio-distribution / integration profiles were performed more than a decade ago.
The research was prior to initiation of most human clinical trials, and continues to be referenced as the established precedent for a lack of detectable bio-distribution / integration.
Read that again! The research was PRIOR TO INITIATION of most HUMAN clinical trials, and CONTINUES to be referenced as the ESTABLISHED PRECEDENT for a lack of detectable bio-distribution / INTEGRATION.
In light of the numerous DNA vaccine trials in progress, it might be prudent to re-evaluate this question using highly sensitive molecular biology technologies, commonly employed by the gene therapy field, to profile the human genome for putative sites of insertional mutagenesis.
I'm not making this up. It's stated in the 2016 study, which clearly uncovers a very serious underlying safety concern involving FDA protocol, as it pertains to DNA vaccines and their potential to integrate into the human genome.
Upon first glance, it does appear that scientists are confident in the DNA vaccine, and that insertion into the host genome has been ruled out. But upon further investigation we find this is not the case, since test methodologies are outdated, yet the old paradigm persists.
