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Both the AstraZeneca and J&J vaccines use an adenovirus to deliver DNA instead of mRNA wrapped in lipid (like Moderna & Pfizer). Everywhere I read about the J&

Both the AstraZeneca and J&J vaccines use an adenovirus to deliver DNA instead of mRNA wrapped in lipid (like Moderna & Pfizer). Everywhere I read about the J&J vaccine, I see something like "the DNA vaccine doesn't alter your DNA". Can somebody please clear this up? As far as I understand, the mRNA just stays in the cytoplasm of the cell and gets used up by the ribosome to create spike proteins. The adenovirus vector used in the J&J (and other vaccines) injects DNA in the cell's nucleus, which seems at odds with the widely circulated "it doesn't change your DNA" statement. Do people make this claim because the cell displaying spike proteins is basically always eliminated by CD8 killer T cells? Btw here's a nice high-level summary by the NYT about how all the vaccines work: https://www.nytimes.com/interactive/2021/health/how-covid-19-vaccines-work.html https://www.nytimes.com/interactive/2021/health/how-covid-19...

ceejayoz 5y ago
Being in the nucleus and being integrated into your chromosomes so that they are copied during cell division aren't the same thing. https://www.medpagetoday.com/special-reports/exclusives/91604 https://www.medpagetoday.com/special-reports/exclusives/9160... > Adenoviruses -- even as they occur in nature -- just do not have the capacity to alter DNA. Unlike retroviruses such as HIV or lentiviruses, wild-type adenoviruses do not carry the enzymatic machinery necessary for integration into the host cell's DNA. That's exactly what makes them good vaccine platforms for infectious diseases, according to Coughlan. > And, engineered adenoviruses used in vaccines have been further crippled by deleting chunks of their genome so that they cannot replicate, further increasing their safety.
- dahfizz 5y ago
  This sounds a bit like a technicality. The DNA makes it into the cell nucleus and is used by the cell machinery to make proteins. The changes aren't carried over after cell division, but lots of cells in your body last your whole life (nerves, brain cells, eye cells, important stuff).
  - ipaddr 5y ago
    I was under the impression all cells in the body will be regenerated in 7 years.
    - laplacesdemon48 5y ago
      Loss of neurons and cardiac muscle cells is permanent. Emergency medical personnel are usually taught "time is brain" and "time is heart" for this reason. Some body cells can bounce back after serious trauma, liver cells being a prime example: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2701258/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2701258/
chaorace 5y ago
I think the argument hinges on the technicality that it's not splicing itself into the host genome, so no chance of it becoming a retrovirus or something like that (in the event that the cell's lineage is not extinguished by the immune system). I'm not a genetic engineer (what a time to be alive, eh?), but I'm pretty sure an adenovirus that did permanently modify cell DNA would be more like CRISPR, including the risks that entails (such as the risk of incorrectly splicing the host genome and potentially creating a precancerous mutation)
- laplacesdemon48 5y ago
  I didn't want to put this into the parent comment because I didn't want to get just shoved into the "vax" vs. "anti-vax" bucket by the replies. But there's a very well known case where DNA delivered via an adenovirus killed a teenager during a genetic engineering study: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC81135/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC81135/ >> "No one realized that the vector itself might pose a risk" I'm sure the dosage, type of adenovirus, and modifications to the adenovirus are different. But there are obviously still risks we don't know about.
  - ghthor 5y ago
    Don't look at things like that. Shut down your brain and take your pilllls.
    - laplacesdemon48 5y ago
      I want to be perfectly clear that I didn't bring this up to be alarmist. Jesse Gelsinger's death shed a lot of light on the risks involved with adenoviruses [1]. Those lessons have been carried forward. >> An autopsy and subsequent studies indicated that his death was caused by a fulminant immune reaction (with high serum levels of the cytokines interleukin-6 and interleukin-10) to the adenoviral vector. >> The data suggested that the high dose of Ad [adenoviral] vector, delivered by infusion directly to the liver, quickly saturated available receptors ... within that organ and then spilled into the circulatory and other organ systems including the bone marrow, thus inducing the systemic immune response. He was injected with >3 × 10^13 viruses [2]. The typical J&J dose contain: low-dose (5x10^10 viral particles) or high-dose (1x10^11 viral particles) [3]. [1] https://www.uab.edu/ccts/images/steinbrook_Gelsinger_-_Oxford_Textbook_08_3.pdf https://www.uab.edu/ccts/images/steinbrook_Gelsinger_-_Oxfor... [2] https://www.cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016(20)30096-4 https://www.cell.com/molecular-therapy-family/molecular-ther... [3] https://www.jwatch.org/na53085/2021/01/26/adenovirus-vectored-johnson-johnson-sars-cov-2-vaccine https://www.jwatch.org/na53085/2021/01/26/adenovirus-vectore...
carnivalWilson 5y ago
I'm a bioengineer. Everyone that gives an answer mostly ignores epigenetics and the fact that RNA can permanently alter the _shape_ (or conformation) of how your DNA is tightly wound up. For example, RNA can direct methylation of DNA and alter histones, which can lead to transgenerational epigenetic effects on gene expression and phenotype [1]. The fact is, molecular cell biology is incredibly complex and the models we have are just that, models. Saying that these mRNA strands don't affect the genome long-term may be correct, but this is an educated guess based on theoretical models. There's a reason why FDA approvals traditionally took 10+ years, we normally verify our educated guesses empirically. It almost certainly won't have long-term affects, but it may not be trivial to identify if mRNA vaccines have been altering epigenetics. [1] https://en.wikipedia.org/wiki/RNA-directed_DNA_methylation https://en.wikipedia.org/wiki/RNA-directed_DNA_methylation
- splithalf 5y ago
  Everything in life has potential epigenetic effects! Not sure what you are trying to communicate with your comment but it sounds like you are saying people should avoid the mRNA vax but then you also say “almost certainly no long term effects.” Your thesis seems to be that 10 years is enough time to know for sure that they are safe. Why is 10 years the right amount of time? Why not 50 years or 5? In other words what’s your model for relative risk/reward and why is it better than what is being done in terms of public health outcomes?
  - base698 5y ago
    50 would certainly cover all life stages of humans. I assume you could be sure with shorter. I have an aviation, biochem, and skydiving background. My rule is for aviation: "if it hasn't been out five years you're a test jumper." Humans are way more complex than airplanes. I personally wouldn't take the mRNA vaccine because of this rule. Coupled with being unable to sue or get help from the government I think people IN LOW RISK groups have been way too enthusiastic to sign up. https://www.cnbc.com/2020/12/16/covid-vaccine-side-effects-compensation-lawsuit.html https://www.cnbc.com/2020/12/16/covid-vaccine-side-effects-c...
UncleOxidant 5y ago
Whenever you catch a cold or flu those are generally DNA viruses (unless it's a coronavirus cold). Those don't alter your DNA.
- base698 5y ago
  Eh, yeah they do. We have tons of base pair sequences in our DNA that we suspect came from viruses. https://newsroom.uw.edu/news/genes-%E2%80%98fossil%E2%80%99-virus-human-dna-found-be-active https://newsroom.uw.edu/news/genes-%E2%80%98fossil%E2%80%99-...
  - Pyramus 5y ago
    Parent specifically stated DNA viruses. From your article: > Most of these viral genes come from retroviruses, RNA viruses that insert DNA copies of their own genes into our genomes when they infect cells. HHV-6 is unique because it is the only known human DNA herpesvirus that integrates into the human genome and can be routinely inherited.

ceejayoz 5y ago

Being in the nucleus and being integrated into your chromosomes so that they are copied during cell division aren't the same thing. https://www.medpagetoday.com/special-reports/exclusives/91604 https://www.medpagetoday.com/special-reports/exclusives/9160... > Adenoviruses -- even as they occur in nature -- just do not have the capacity to alter DNA. Unlike retroviruses such as HIV or lentiviruses, wild-type adenoviruses do not carry the enzymatic machinery necessary for integration into the host cell's DNA. That's exactly what makes them good vaccine platforms for infectious diseases, according to Coughlan. > And, engineered adenoviruses used in vaccines have been further crippled by deleting chunks of their genome so that they cannot replicate, further increasing their safety.

dahfizz 5y ago
This sounds a bit like a technicality. The DNA makes it into the cell nucleus and is used by the cell machinery to make proteins. The changes aren't carried over after cell division, but lots of cells in your body last your whole life (nerves, brain cells, eye cells, important stuff).
- ipaddr 5y ago
  I was under the impression all cells in the body will be regenerated in 7 years.
  - laplacesdemon48 5y ago
    Loss of neurons and cardiac muscle cells is permanent. Emergency medical personnel are usually taught "time is brain" and "time is heart" for this reason. Some body cells can bounce back after serious trauma, liver cells being a prime example: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2701258/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2701258/

chaorace 5y ago

I think the argument hinges on the technicality that it's not splicing itself into the host genome, so no chance of it becoming a retrovirus or something like that (in the event that the cell's lineage is not extinguished by the immune system). I'm not a genetic engineer (what a time to be alive, eh?), but I'm pretty sure an adenovirus that did permanently modify cell DNA would be more like CRISPR, including the risks that entails (such as the risk of incorrectly splicing the host genome and potentially creating a precancerous mutation)

laplacesdemon48 5y ago
I didn't want to put this into the parent comment because I didn't want to get just shoved into the "vax" vs. "anti-vax" bucket by the replies. But there's a very well known case where DNA delivered via an adenovirus killed a teenager during a genetic engineering study: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC81135/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC81135/ >> "No one realized that the vector itself might pose a risk" I'm sure the dosage, type of adenovirus, and modifications to the adenovirus are different. But there are obviously still risks we don't know about.
- ghthor 5y ago
  Don't look at things like that. Shut down your brain and take your pilllls.
  - laplacesdemon48 5y ago
    I want to be perfectly clear that I didn't bring this up to be alarmist. Jesse Gelsinger's death shed a lot of light on the risks involved with adenoviruses [1]. Those lessons have been carried forward. >> An autopsy and subsequent studies indicated that his death was caused by a fulminant immune reaction (with high serum levels of the cytokines interleukin-6 and interleukin-10) to the adenoviral vector. >> The data suggested that the high dose of Ad [adenoviral] vector, delivered by infusion directly to the liver, quickly saturated available receptors ... within that organ and then spilled into the circulatory and other organ systems including the bone marrow, thus inducing the systemic immune response. He was injected with >3 × 10^13 viruses [2]. The typical J&J dose contain: low-dose (5x10^10 viral particles) or high-dose (1x10^11 viral particles) [3]. [1] https://www.uab.edu/ccts/images/steinbrook_Gelsinger_-_Oxford_Textbook_08_3.pdf https://www.uab.edu/ccts/images/steinbrook_Gelsinger_-_Oxfor... [2] https://www.cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016(20)30096-4 https://www.cell.com/molecular-therapy-family/molecular-ther... [3] https://www.jwatch.org/na53085/2021/01/26/adenovirus-vectored-johnson-johnson-sars-cov-2-vaccine https://www.jwatch.org/na53085/2021/01/26/adenovirus-vectore...

carnivalWilson 5y ago

I'm a bioengineer. Everyone that gives an answer mostly ignores epigenetics and the fact that RNA can permanently alter the _shape_ (or conformation) of how your DNA is tightly wound up. For example, RNA can direct methylation of DNA and alter histones, which can lead to transgenerational epigenetic effects on gene expression and phenotype [1]. The fact is, molecular cell biology is incredibly complex and the models we have are just that, models. Saying that these mRNA strands don't affect the genome long-term may be correct, but this is an educated guess based on theoretical models. There's a reason why FDA approvals traditionally took 10+ years, we normally verify our educated guesses empirically. It almost certainly won't have long-term affects, but it may not be trivial to identify if mRNA vaccines have been altering epigenetics. [1] https://en.wikipedia.org/wiki/RNA-directed_DNA_methylation https://en.wikipedia.org/wiki/RNA-directed_DNA_methylation

splithalf 5y ago
Everything in life has potential epigenetic effects! Not sure what you are trying to communicate with your comment but it sounds like you are saying people should avoid the mRNA vax but then you also say “almost certainly no long term effects.” Your thesis seems to be that 10 years is enough time to know for sure that they are safe. Why is 10 years the right amount of time? Why not 50 years or 5? In other words what’s your model for relative risk/reward and why is it better than what is being done in terms of public health outcomes?
- base698 5y ago
  50 would certainly cover all life stages of humans. I assume you could be sure with shorter. I have an aviation, biochem, and skydiving background. My rule is for aviation: "if it hasn't been out five years you're a test jumper." Humans are way more complex than airplanes. I personally wouldn't take the mRNA vaccine because of this rule. Coupled with being unable to sue or get help from the government I think people IN LOW RISK groups have been way too enthusiastic to sign up. https://www.cnbc.com/2020/12/16/covid-vaccine-side-effects-compensation-lawsuit.html https://www.cnbc.com/2020/12/16/covid-vaccine-side-effects-c...

UncleOxidant 5y ago

Whenever you catch a cold or flu those are generally DNA viruses (unless it's a coronavirus cold). Those don't alter your DNA.

base698 5y ago
Eh, yeah they do. We have tons of base pair sequences in our DNA that we suspect came from viruses. https://newsroom.uw.edu/news/genes-%E2%80%98fossil%E2%80%99-virus-human-dna-found-be-active https://newsroom.uw.edu/news/genes-%E2%80%98fossil%E2%80%99-...
- Pyramus 5y ago
  Parent specifically stated DNA viruses. From your article: > Most of these viral genes come from retroviruses, RNA viruses that insert DNA copies of their own genes into our genomes when they infect cells. HHV-6 is unique because it is the only known human DNA herpesvirus that integrates into the human genome and can be routinely inherited.