[kaczordon]

Right but they are still gene-based. No gene-based vaccine has ever received approval for human use, and the present coronavirus vaccines have not undergone preclinical testing as normally required by international regulations.

A potential danger of DNA-based vaccines is the integration of plasmid DNA into the cell genome (1). Insertional mutagenesis occurs rarely but can become a realistic danger when the number of events is very large, i.e. as in mass vaccination of a population.

(1) https://www.nature.com/articles/3302213

[maxerickson]

That's a different technology than the Adenovirus vectors.

There's no plasmids in the Covid vaccines, a virus has been modified to include instructions for the target proteins.

Edit: plasmids are used to encode the virus for production, they aren't part of the delivery mechanism: https://www.addgene.org/viral-vectors/

[tylerhou]

Also,

> and the present coronavirus vaccines have not undergone preclinical testing as normally required by international regulations.

Citation needed.

[kaczordon]

https://www.fda.gov/vaccines-blood-biologics/vaccines/emerge... there's a reason it's emergency authorization, we don't have long term data yet.

[tylerhou]

You said vaccines haven't undergone preclinical testing; where is the evidence of that? All EUA vaccines have undergone animal tests.

[strikhedonia]

We don’t have “long term data” for the next week or two, anyway. Phizer and Moderna’s chances of winning full use authorization this spring look quite good.

[tylerhou]

I'm not a biologist, so I could be completely wrong here, but I disagree with you.

First of all, plasmid != viral vector. That's why the Nature paper you cited had to use electroporation to introduce the payload. As J&J is a viral vector vaccine, I would not be confident in using this paper to make the argument that an adenovirus-based vaccine could modify a host's DNA.

Second, your article does not make the claim you think it does. Specifically, the discussion says:

> Using simple intramuscular injection, the vast majority of plasmid DNA that persists is extrachromosomal, and the frequency of integration, if it occurs at all, is negligible.

> However, even if the residual plasmid in the gel-purified genomic DNA did represent integrated plasmid, one copy... would be at least three orders of magnitude below the frequency of spontaneous gene-inactivating mutations...

That is, the delivered gene does not integrate directly into the genome itself, but rather stays in the cell. To detect whether the gene stays in the host cell, the article compares molecular weight and uses a PCR test. Both methods do not tell us whether the gene inserts itself into the host DNA; one way to detect that would be to sequence the subsequent DNA, which would be monstrously expensive (because the modification incidence is extremely low).

The only way that a gene might integrate itself into the chromosome is if during DNA transcription, an error occurs and the foreign DNA is merged onto the host DNA. But this would be incredibly rare because it would require most base pairs to match up between the host & foreign DNA; otherwise, the cell would attempt to repair itself or induce apoptosis.

And even if the resulting base pairs match up, the resulting DNA might not have any behavioral differences because it's (approximately) the same sequence of characters. (And you would need another transcription error later on that happens to reduce the non-modified strand by approximately the same length. That's also extremely unlikely.)

Fourth, the Pfizer and Moderna vaccines use a mRNA-based vector, which (in my limited knowledge) is very difficult to integrate into the genome. The most plausible mechanism I could imagine would be:

1. (Optional) an enzyme which converts a modified nucleoside mRNA strand into one that mimics the mRNA chemical structure that is compatible with a reverse transcription enzyme [1].

2. A reverse transcriptase to convert the mRNA strand into a (foreign) DNA strand.

3. A restriction enzyme that cleaves the host DNA suitably so that the foreign DNA can be inserted.

4. A matching ligation enzyme which actually inserts the foreign DNA into the the host DNA.

All these above enzymes do not naturally occur in humans, so DNA modification through this mechanism would be incredibly rare.

[1] https://link.springer.com/protocol/10.1007/978-1-4939-6481-9...

[kaczordon]

Ermm, the jnj uses an adenovirus to deliver the plasmid DNA(1). I'm only referring to the jnj/astra here not the mRNA ones. And I think that article I linked represents a real risk it's not like we've tested for this danger before going ahead with a mass vaccination campaign where even rare events can become a real danger.

Additional dangers of DNA vaccines include production of anti-DNA antibodies and autoimmune reactions(2). I think we should be communicating these dangers to the public so that healthy individuals at no risk can make a proper benefit-risk decision, instead of just saying "vaccines good" and brushing over concerns.

(1) https://coronavirus.medium.com/decoding-johnson-johnsons-cov...

(2) https://link.springer.com/protocol/10.1007/978-1-62703-110-3...

[tylerhou]

> I think that article I linked represents a real risk

The article you linked estimates the risk of DNA integration is three orders of magnitude times lower than gene deactivation through regular mutations. I think we're safe.

> Additional dangers of DNA vaccines include production of anti-DNA antibodies and autoimmune reactions

Any documented cases in clinical trials?

[kaczordon]

Sigh yes this is a well recognized risk which even the FDA has guidelines for: "The administration of a DNA vaccine exposes the patient to foreign DNA or its fragments that could be inserted into the host’s chromosomal DNA [70]. In the case of incorporation into an exon, an insertional mutation or a frameshift mutation occurs. Such mutations can cause a gene to malfunction or inactivate (i.e., a tumor suppressor gene). The insertion of foreign genes into the host genome could also lead to constituent expression of previously silent bacterial/parasite genes that have been inserted."(1)

To date, there is no licensed DNA vaccine for use in humans, which is my whole point we aren't testing for this and instead just using the whole US population as test subjects without informing them of the risk.

(1) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105045/