Also: the side effect profile for the moderna and pfizer vaccines in the clinical trials was far WORSE than the jnj vaccine.
Edit: gene-based not gene-therapy
The risks could be higher, but maybe our data is not yet there.
Just as a side note, the risks (and gains) are different, maybe I really don't want a child accidentally, but I don't consider the coronavirus too dangerous to me (it's just a hypothetical, this hypothetical person could be wrong, but in the end we all operate on incomplete data)
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.
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...
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...
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?
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.
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/
> and the present coronavirus vaccines have not undergone preclinical testing as normally required by international regulations.
Citation needed.
In this pandemic, inaction costs lives. The logical and ethical thing to do is evaluate the cost/benefit and choose the path that kills fewer people. You wouldn't say "we should exit the burning house one at a time in case we get hit by a meteor outside, caution here is the logical and ethical thing"; you're making the same kind of logical error, just with a less-absurd difference between the risk of the two options we need to choose between.
I always appreciate an apt analogy.
The type of blood clots (low platelet) the J&J causes gets worse with the standard treatment of blood thinners. This was on the CDC call this morning.