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Is there any plausible mechanisms for why taking an mRNA vaccine might be undesirable for a young healthy adult?

by Mati_Roy1 min read8th Apr 202111 comments

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We haven't seen any problem in the short term, but is the probability of long term negative side effects (given it's a new technology) sufficiently unlikely for a young healthy person to take it?

Am particularly concerned with unknowns long-term future negative side effects, but which we might be able to estimate from first principles, or through some more abstract reference class, or something.

I already fully isolate, and would only value my freedom a bit, whereas I value my health a lot.

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The main concern I had was that it leads to a development of polyethylene glycol resistence. After talking this through with a doctor, I now believe that 1-2 doses of the vaccine are unlikely to have a significant effect but still some that giving significantly more doses (for example 2 every year to target changing viruses) could lead to such an effect. 

I already fully isolate, and would only value my freedom a bit, whereas I value my health a lot.

Human contact is very important for human health. The idea that you can fully isolate without paying a price for it in health seems questionable to me. Humans are not constructed to live healthy lifes in isolation from other humans.

well, I should unpack "fully isolate" (I meant fully isolate from the virus):

  • I isolate with another human
  • I video-chat with multiple humans
  • I chat in person with other humans outside with 3 meters distance or insider with a full-face mask :)

What is polyethylene glycol resistance? Google isn't turning much up. Or do you mean sensitivity / allergy?

6ChristianKl8moAntibody buildup against polyethylene glycol or PEG. One issue of concern was voiced in The Importance of Poly(ethylene glycol) Alternativesfor Overcoming PEG Immunogenicity in DrugDelivery and Bioconjugation [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7077443/]: Polyethylene glycol or PEG is the lipid with which the mRNA is coated and it seems the body starts attacking it with repeated treatments. This means repeated usage of drugs that contain PEG reduces the efficiency per dose and increases side effects. However after speaking with a doctor who told me a lot about the involved gears, I don't think this is a huge deal for giving a human two doses of an mRNA vaccine.

Epistemic status: someone told me that someone that knew about this told them that

mRNA vaccines have been done on non-human animals for decades, and they seem fine

The mRNA tricks your cells into making a spike protein

The alternative is the live adenovirus vector, which tricks your cells into making a spike protein PLUS all the other proteins that make up the adenovirus.

So it seems like the former probably can't be any worse unless it "infects" different types of cells.

I thought of a second potential problem in my layman armchair.  Every cell that a virus infects, it kills (when the cell dies, the new viruses pop out).  But what if the mRNA for a single protein just messes up a cell, without killing it?   Possibly worse than just killing it.

The new lipid nanoparticle delivery method can potentially target a much wider range of cells than older modalities. Any cell can ingest an LPN and start displaying spike protein epitopes. All the cells that are not professional presenter cells and do not have MHC-2 complexes will be destroyed by immune system. Some critical, sensitive, hard to replace cells might be so killed at random if enough LPN get into systemic circulation which can occur if for example a needle pierces a blood vessel during vaccination and a large portion of LPN spills into the veins. The chance of this type of accident and the chance that significant damage to your organs will be done as a result is not very big, but it is a risk which you will be taking every time you vaccinate.

I'm not a biologist, and bodies are complicated enough that I'd like an answer to this too.

 

But to a first glance from a layman: I have a hard time understanding what mechanisms there might be, especially age-dependent ones. The sugars, salts, acids, and stabilizers all either occur naturally in the body or have been used medically long enough to have their risk profiles known. I don't know about the specific lipids used, can't comment there. mRNA only survives in the body for a matter of hours, after that what's present is just the proteins you made from the mRNA, which should work the same way as identical viral-derived proteins would, generating an immune response by the same mechanism.

Instead of an either/or decision based on first principles, you might frame this as a "when" decision based on evidence.  We've had about 4 months of real-world experience with the mRNA vaccines... if you wait another 4 months, that's double the track record, and it's always possible that new options will open up (say, a more traditional vaccine that's more effective than J&J).

The converse of that is that 225 million doses have been given and the serious negative effect rate is extremely low.  It's improbable that merely another doubling of time and doses will reveal any new information.  

If there is some new way this method causes the human body to fail it won't be found for years.  

Conversely, there's still the risk of Covid, and isolation has holes.  The biggest one being you might get sick and have to see medical treatment, and hospital acquired infections are estimated to happen 1.7 million times a year.  And while being young your odds are good, there are illness 'stacks' where Covid would kill you.  (some respiratory or autoimmune illness as well as covid at the same time, etc)