Infection_Ag11 said:

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Gumby said:

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Are there any potential side effects or downsides? Isn't this essentially altering our DNA in some way? Could it lead to genetic mutations or cancer? What kind of safety data do we have? Any long-term studies?

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It doesn't alter your DNA, it essentially hijacks your ribosomes and causes them to translate foreign RNA to produce a foreign protein (in this case, the COVID spike protein) which is then released from the cell and your body forms antibodies to it.

My concern isn't with respect to altering DNA, but rather the theoretical risk of developing additional derivative proteins via various mechanisms and generating a type of autoimmune response. It's entirely theoretical though and may end up being entirely baseless on my part.

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correct, mRNA is not insertional into the genome.

how long does the mRNA you're injected with stay in your body?

cone said:

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how long does the mRNA you're injected with stay in your body?

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seconds, minutes, or hours. using a lipid nanoparticle increases its life. it only needs to be long enough to attach to a ribsome for translation.

cone said:

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how long does the mRNA you're injected with stay in your body?

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we encode multiple mRNAs into cocktails to create multiple proteins. however you only have limited ribosomes so the dominant ones tend to overtake and attach more frequent. so it's a game of cat and mouse. we have created proteins that multiply in the upwards of 100,000,000,000 per ml.

and once the ribosome makes the protein as directed by the RNA, is that it for what the vaccine actually does?

then the body responds to the proteins created by the ribosomes and provokes an immune response creating antibodies

so what happens eventually to those spike proteins you briefly manufactured, are they eventually discarded as well, leaving only the antibodies remaining (and the bodies memory with regard to how to get antibodies quickly in response to those spike proteins)?

I'm just a dumbass engineer so take pity on me. I'm mostly concerned with what's left over in the weeks/months following the initial immune response.

also, just to better understand but the breakthroughs here are:

- the tech to sequence the virus
- the tech to build the mRNA sequence needed to create the protein that would provoke the antibody production
- the tech to manufacture the mRNA
- the tech to envelope the mRNA in a nano-capsule lipid layer that can survive entry into the cells

otherwise the method in which the cells receive mRNA instructions to get the antigen production going (usually from inactivated virus with regular vaccines) is the exact same as always. it's just that we're cutting out the middle man (inactivated virus) through breakthroughs in bio component production (mRNA in nano-shells).

so any auto-immune complications would be under the subset of vaccinations as a whole, not just this platform.

The simple answer is yes, everything in the vaccine is transient, but the immunity generated should be long lasting.

In that sense it's not different than an old school vaccine where they give you some dead virus. The dead virus induces an immune response and then is cleared.

Here mRNA gets into your cells and makes part of the virus. The mRNA doesn't last long in your system, and neither do the viral proteins it makes. But if you get a good immune response against those proteins then you get protection.

The greatest advance with this method is that making a new mRNA to put in the next vaccine is way easier than trying to make dead virus (or make the protein). So a process that used to take 10 years now takes 10 months. The next vaccine made this way won't be nearly as rushed (because hopefully we're done with pandemics for a bit) but efficiencies from doing it a second, third, or tenth time should speed the process. So SARS-V3 shouldn't stand a chance.

The auto immune component will probably be specific to the vaccine. If the part of the virus we target looks like something that's already in your body, bad things can happen. Also some people may just have an overly aggressive immune response. But I don't see anything about the mRNA technology that makes that risk worse.

thank you for the response!

Fitch said:

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I would add the networking of (tens of?) thousands of privately owned computers and gaming consoles to aid in the computing power needed to run untold numbers of protein folding simulations.

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I forgot about this!

I don't think it'll speed things up too much. The time to run Phase 1/2/3 trials still adds up even if the time to make the first dose is less.

Infection_Ag11 said:

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It's definitely not getting the appreciation it should, even within the medical community. It's at least on the level of HAART and curing hepatitis C, and arguably could be the greatest medical achievement since the eradication of smallpox. And to get it done so quickly? Truly a remarkable testament to human ingenuity.

My only concerns are one, any long term complications that arising from essentially reprogramming our cells to produce foreign antigens and two (related to one) the public's fear of a "new" type of vaccine. It's hard enough to get people to take inactivated and recombinant protein vaccines, imagine those same people reading the layman explanation for this.

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Well, they have been working on it for over a decade.

mRNA is temporary. It isn't like a change to the DNA. Once the injected batch of mRNA degrades, you can't make any more antigen. Also, any cell that gets the mRNA and starts producing the antigen should get targeted for destruction by the immune system.

Gumby said:

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KidDoc said:

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Gumby said:

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Are there any potential side effects or downsides? Isn't this essentially altering our DNA in some way? Could it lead to genetic mutations or cancer? What kind of safety data do we have? Any long-term studies?

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It does nothing to your DNA. Here is a short 2 minute YouTube about the mechanism.

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Thanks for sharing. Are there any potential negative consequences of sending your cells a set of instructions to produce a protein and corresponding antibodies? Is there any potential the body could misinterpret them?

I'm completely ignorant but see many people saying these RNA vaccines could lead to cell mutations. The people saying that may be ignorant as well but the fear is out there.

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You are only sending the cells the instructions to produce the protein. The immune system figures out how to produce the antibodies in the normal fashion.

Also, consider that when infected with COVID, the virus will produce mRNA to make spike protein inside the cells it infects. The mRNA vaccine is doing the same thing, but without the virus being able to replicate since none of the rest of the virus is encoded in the mRNA.

and the antigen is sufficiently different from any other protein such that you'd avoid an autoimmune backfire?

and the mRNA is quality tested already to insure it makes only the protein it was designed to make?

cone said:

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and the antigen is sufficiently different from any other protein such that you'd avoid an autoimmune backfire?

and the mRNA is quality tested already to insure it makes only the protein it was designed to make?

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I supposed an autoimmune backfire is always a risk. The immune system tries out a bunch of antibodies and selected what works well, but also is supposed to select against anything that targets self. Obviously, the later part doesn't always work. Also, it isn't that the antigen as a whole is different, that would actually be pretty easy. We know the structure (cryoEM was published back in Feb I believe). The issue is antibodies target small patches of the surface of the protein. However, this is not really that different a risk than the virus causing an autoimmune backfire, except the virus has many more proteins so with each additional protein, you increase the chance of an autoimmune response.

We have a pretty good understanding of how RNA encodes proteins. You need start and stop codons and you make a protein of everything in between. Pretty easy to check and ensure you don't have any extra start/stop codons that could make a portion of the protein or be shifted to make something completely different in a different frame. We also have a pretty good understanding of splicing and other modifications and should be able to design to avoid those issues.

so if done correctly, these experimental vaccines should actually be safer

and any autoimmune issue would be noticeable within the time frame of the safety trial

that is to say that by the time normal healthy people get the shots, tens of thousands of people will have been living with having received the vaccine for nine months, at least

cone said:

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so if done correctly, these experimental vaccines should actually be safer

and any autoimmune issue would be noticeable within the time frame of the safety trial

that is to say that by the time normal healthy people get the shots, tens of thousands of people will have been living with having received the vaccine for nine months, at least

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Yes this sounds accurate.

I want it sooner rather than later not due to my own personal risk of severe COVID but because I am not being given PPE by my employer to see my sick patients- they are all being sent to a central clinic to conserve equipment and cost.