Comment by programmarchy | Hacker News Reader

Comment by programmarchy | Hacker News Reader

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Do we really know this? Obviously the spike proteins are using an existing mechanism (ACE2) in our bodies to bind to cells. Of primary importance to both viruses and our reproductive system is the membrane fusion function for instance. We must also consider how our bodies developed in the first place; “RNA world” and “virus world” theories predict our genetics evolved from RNA-based processes or even a primordial graveyard of viral RNA.

We also don’t fully understand what causes autoimmune disease, but various environmental causes have been explored including bacterial and viral infections. Presumably if a viral infection could trigger an autoimmune response in certain genetically predisposed groups, then so could a vaccine designed to mimic a virus.

Unfortunately the incentives in our medical system are not designed to find cures for autoimmune diseases, although they are very much incentivized for palliative care, so progress has been painfully slow in understanding the deeper complexities of the immune system.

> Presumably if a viral infection could trigger an autoimmune response in certain genetically predisposed groups, then so could a vaccine designed to mimic a virus.

This is true. Some of the extremely rare auto-immune issues that have impacted people who have been vaccinated for specific flu viruses in, IIRC, 1976 and 2009, were thought to occur at even higher rates and severity with people who contracted the virus. So, vaccination might impact you, but likely worse the the virus itself due to the greater amount of virus in your system.

I am not a scientist, but I would expect that the mRNA vaccines would have less of a chance of having an auto-immune reaction since they contain only one of the many proteins contained in the actual virus.

Yeah, I’m actually very hopeful that mRNA medicine will be able to overcome issues like these in ways traditional vaccines couldn’t. For example, variations could be developed that are more effective for each racial group, rather than a one-size-fits all approach that may be biased. From there, perhaps even individuals who have autoimmune disease markers could have variants developed for them as well.

>I am not a scientist, but I would expect that the mRNA vaccines would have less of a chance of having an auto-immune reaction since they contain only one of the many proteins contained in the actual virus.

This is the angle that, for me, is suppressing my innate concern for a widescale and rapid application of a brand new immunological therapy. It's extremely targeted and feels like the future. I can imagine a day where the FDA approves the process rather than the instance of mRNA-based therapies, allowing for highly personalized treatment.

I believe this is one of the reason a Harvard Professor was pushing for a 3 month extended phase 3/4 trial.

This was recently noted in a AMA by virus experts on reddit.

> Do we really know this? Obviously the spike proteins are using an existing mechanism (ACE2) in our bodies to bind to cells.

Sure, but aren't the proteins produced by the vaccine virtually identical to the ones produced by the actual virus?

If so, the calculus looks like this:

1) Take the vaccine and accept the (unknown, but apparently quite small) probability that something in your body will react very negatively to the generated viral proteins.

2) Get the virus, accept the probability (also unknown, but the same as in 1) that something in your body will react very negatively to the viral proteins, plus accept the additional risk of being infected by the actual virus.

I guess the third possibility would be to refuse the vaccine and gamble that you won't get the virus, either.

Or have the virus already and get immunity in that way.

That would be the same as 2, in terms of risk from the body reacting negatively to the viral proteins.

and possibly infect scores of other people, some of them not so lucky and will get the serious case requiring hospitalisation or worse.

It’s not clear if the vaccine will prevent infectiousness yet, unfortunately, so for now it’s best to assume even vaccinated people can spread the virus until more is known. Both ways will increase herd immunity.

I generally agree with you. Keep in mind I'm at 'stayed at the Holiday Inn' levels of competence here, but in my mind the spike proteins that are generated by an actual infection don't typically leave the cytoplasm detached from the rest of the virus. This could be incorrect.

If that's generally true, the difference here would be that the part of the spike protein topology that is typically bound to other proteins in an actual infection would be accessible to the immune system in the case of a vaccination. I think that is where the differential risk could occur with a vaccination that wouldn't occur with an actual infection (however small that might be).

In my daughter's case, something happened when she was about 14 years old that caused her body to determine that the beta cells in her pancreas were invaders and have to die, so I'm just tuned into this kind of possible side effect.

> (...) but in my mind the spike proteins that are generated by an actual infection don't typically leave the cytoplasm detached from the rest of the virus.

If the virus is destroyed and released into the extracellular environment, its proteins can dissociate and are further fragmented and processed by the immune system. What’s usually presented to T cells are small antigen pieces as opposed to the whole virus/protein.

This is a great point thank you.

> in my mind the spike proteins that are generated by an actual infection don't typically leave the cytoplasm detached from the rest of the virus

Virus takes over the cell, makes the cell to manufacture components of the virus and to assemble viruses, until this disrupts the cell so bad that the cell dies and typically bursts. Surely at this point, not only assembled viruses, but also components at different stages of production, are released?

https://en.wikipedia.org/wiki/Introduction_to_viruses#Life-c...

Thank you. I knew this at some level but this (amazing) animation of HIV got me on a track of thinking that the viruses have a mechanism for exiting the cell without destroying it:

https://vimeo.com/260291607

Like the Wikipedia article says, most viruses make the cell burst. Some, like HIV, have less destructive methods. I could not find how SARS-CoV-2 does it.

> Keep in mind I'm at 'stayed at the Holiday Inn' levels of competence here

OT, but what does this mean or refer to? I'm curious :)

https://youtu.be/eHCTaUFXpP8

Corny but fun, they had a few good ones.

I read that the immune system doesn't usually produce antibodies for the spike protein when fighting the virus, i think it was a membrane protein that was more commonly targeted, and we didn't understand why.

I was just going to ask this question. Do you happen to recall where you read it?

https://medicalxpress.com/news/2020-12-covid-vaccines-focus-...

I was wrong, its the nucleocapsid protein, not the membrane one, but that's even weirder as the N protein is only found inside the virus particle..

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