I'll start with a breakdown of how RNA vaccines work.
They deliver an mRNA sequence into your body. mRNA is a relatively short-lived form of RNA that is transcribed into protein a handful of times before being degraded by endonucleases [1, 2].
As you said, the mRNA in the COVID vaccine encodes the spike protein. When your body's cells encounter it, they produce the spike protein. Every cell in the body presents some of the proteins that it creates on its cell surface in a structure called the major histocompatibility complex I (MHC I). This is the body's built in QA system: immune cells scan these proteins to check if any of your cells have been infected with a virus and are producing viral proteins [3].
When your body's white blood cells encounter spike proteins on the MHC I, an immune response is triggered [3]. This is a very long series of cascading steps, but the important part for us is that it leads to the creation of memory B cells, which are long lived cells that produce antibodies to the offending viral protein [4].
While your body is mounting this response, you develop a fever. Usually 24 - 48 hours after the vaccination. A fever is a sign that your immune system is revving up. As the mRNA degrades and the spike protein is cleared out, the immune system winds back down and the fever dissipates.
But the memory B cells stick around. The next time your body encounters the spike protein, the antibodies produced by memory B cells latch onto the protein and start a chemical reaction that triggers a fast-tracked immune response.
> the body is trained on the wrong thing and still making classic spike proteins... Plus, you don't want the spike protein in your body anyway as apparently that's not a great thing to have around?
No, it is not. The production is only transient. mRNA is a very short lived substance. (See my explanation above.)
It's easy to prove: If you did still have spike protein, you would continue to have fevers. Fever = fulminant immune response [5]. As I said earlier, that's the entire point of a vaccination: to kick start the immune response if even a small amount of the spike protein is detected and reduce the lag time in which the virus could continue to invade cells in your body while your immune system is still revving up [6].
> Suddenly the virus evolves (as we knew they do rapidly and constantly) and now people who got the original vaccine are apparently having worse immune responses because the body is trained on the wrong thing
Well this isn't wrong exactly. But I would say it's a weird way of summarizing the situation.
Why do people get the common cold year after year? Because they have memory cells for last year's strain, not this year's. You could argue that the body wasted resources maintaining those memory cells. But that's just how immunity works. It's not a design flaw of RNA vaccines.
> I'm honestly puzzled why people ever thought the RNA vaccines were worth the time because it doesn't seem like the right mechanism to choose.
RNA vaccines are actually an amazing jump forward in vaccine technology, on the level of the jump from vacuum tubes to transistors in computers [7, 8].
Before RNA vaccines, every vaccine was a bespoke creation. You had to study the virus, find a way to alter its genes so that it's either dead (called an inactivated form) or too weak to cause a serious infection (called an attenuated form), but also still similar enough to the original virus to elicit the same immune response (cross-immunogenicity).
There weren't any good modeling tools for this. It was total trial and error. You had to create the virus, test it on an in vitro or live (i.e. animal) model and see what happened. The iteration time was very slow.
RNA vaccines are a game changer:
1. They allow you to isolate concerns: You can deliver just a chunk of the virus and not the whole thing. No more fiddling around trying to hit the balance between attenuation and cross-immunogenicity because you don't have to care about the biology of the overall virus and how all its components interact [7, 8].
2. They are reprogrammable: You can deliver any RNA sequence you want and thereby manufacture virtually any viral protein you want. If the virus mutates, you can alter the RNA sequence in the vaccine to match without having to rebuild the vaccine from step one [7, 8].
3. They are easily mass produced: It's a lot easier to replicate RNA by PCR than it is to culture a virus [9].
This has big ramifications for turn-around times for developing a new vaccine or refining an existing one. It is honestly a blessing that the technology matured now, as we become increasingly global. It may end up being essential if the next pandemic involves a virus with lethality on the order of smallpox.
> I would appreciate links to literature clarifying them
Most of this is covered in Bio 101 or Immunology 101 college courses, so any introductory text should cover it. Give me a bit of time and I'll try to dig up some specific links for you.
EDIT: Here you go. Citations are provided inline. If you want a general overview, I recommend [6] and [7].
Thank you for the earnest follow-up. I'll read the links, but the key part I was missing was about the mRNA degradation, which folds the rest of my post like a deck-chair. I wish that governments posted a write up similar to this in addition to simple advice guaranteeing safety, as I feel I've seen various partial perspectives on the matter and not assembled the correct whole as a result.
> Once the body creates that spike protein using the mRNA instructions, the body quickly breaks down those mRNA strands and they dissipate within a few hours or days after injection. The mRNA never enters the nucleus of any cell (where the DNA is located), it doesn’t affect any genetic material in the body, and the mRNA strands are removed from the body through everyday cellular processes.
> The Pfizer and Moderna vaccines work by introducing mRNA (messenger RNA) into your muscle cells. The cells make copies of the spike protein and the mRNA is quickly degraded (within a few days). The cell breaks the mRNA up into small harmless pieces. mRNA is very fragile; that's one reason why mRNA vaccines must be so carefully preserved at very low temperatures.
You can follow the links for fuller explanations.
If you want to see hard data, I'm also aware of two studies that investigate how long the spike-protein lingers after vaccination:
Doesn't really inspire confidence in these results, right? I mean, first you cited a claim that said "few hours", and then the expirimental evidence shows at least 5 days, and another one says 10, and may be the next study that looks closer will find that it ll last at least 30 days...
But hey that is ok, because that is how "science" "progresses" duh, right?
EDIT: Oh, and it seems that CDC removed the claim that "The mRNA and the spike protein do not last long in the body" from its pages..
The first source I quoted said a "a few hours or days," but I guess that wasn't convenient for you, so you clipped it.
The numbers 5 and 10 are means. "A few hours or days" represents a range. If you look at the first study, there were several participants who never had detectable spike protein, even when they first checked on day 1 after vaccination. So the spike protein cleared in less than a day for a large chunk of people (i.e. "hours").
As for which study I would trust more, the first study (that reported the shorter period had four times the number of patients). But I guess that is also not convenient for your narrative.
So what? You did say "few hours", right? I am only pointing out the ambiguity in your claims.
>there were several participants who never had detectable spike protein, even when they first checked on day 1 after vaccination.
Look that is fine. But saying "hours or days" is as good as saying we don't have a clue how long the thing lasts in the body. Because, we know that the spike protien itself has toxic effects.
Also I see that you ignored the bit about CDC modifying the statement about this. Not convenient for your narrative?
They deliver an mRNA sequence into your body. mRNA is a relatively short-lived form of RNA that is transcribed into protein a handful of times before being degraded by endonucleases [1, 2].
As you said, the mRNA in the COVID vaccine encodes the spike protein. When your body's cells encounter it, they produce the spike protein. Every cell in the body presents some of the proteins that it creates on its cell surface in a structure called the major histocompatibility complex I (MHC I). This is the body's built in QA system: immune cells scan these proteins to check if any of your cells have been infected with a virus and are producing viral proteins [3].
When your body's white blood cells encounter spike proteins on the MHC I, an immune response is triggered [3]. This is a very long series of cascading steps, but the important part for us is that it leads to the creation of memory B cells, which are long lived cells that produce antibodies to the offending viral protein [4].
While your body is mounting this response, you develop a fever. Usually 24 - 48 hours after the vaccination. A fever is a sign that your immune system is revving up. As the mRNA degrades and the spike protein is cleared out, the immune system winds back down and the fever dissipates.
But the memory B cells stick around. The next time your body encounters the spike protein, the antibodies produced by memory B cells latch onto the protein and start a chemical reaction that triggers a fast-tracked immune response.
> the body is trained on the wrong thing and still making classic spike proteins... Plus, you don't want the spike protein in your body anyway as apparently that's not a great thing to have around?
No, it is not. The production is only transient. mRNA is a very short lived substance. (See my explanation above.)
It's easy to prove: If you did still have spike protein, you would continue to have fevers. Fever = fulminant immune response [5]. As I said earlier, that's the entire point of a vaccination: to kick start the immune response if even a small amount of the spike protein is detected and reduce the lag time in which the virus could continue to invade cells in your body while your immune system is still revving up [6].
> Suddenly the virus evolves (as we knew they do rapidly and constantly) and now people who got the original vaccine are apparently having worse immune responses because the body is trained on the wrong thing
Well this isn't wrong exactly. But I would say it's a weird way of summarizing the situation.
Why do people get the common cold year after year? Because they have memory cells for last year's strain, not this year's. You could argue that the body wasted resources maintaining those memory cells. But that's just how immunity works. It's not a design flaw of RNA vaccines.
> I'm honestly puzzled why people ever thought the RNA vaccines were worth the time because it doesn't seem like the right mechanism to choose.
RNA vaccines are actually an amazing jump forward in vaccine technology, on the level of the jump from vacuum tubes to transistors in computers [7, 8].
Before RNA vaccines, every vaccine was a bespoke creation. You had to study the virus, find a way to alter its genes so that it's either dead (called an inactivated form) or too weak to cause a serious infection (called an attenuated form), but also still similar enough to the original virus to elicit the same immune response (cross-immunogenicity).
There weren't any good modeling tools for this. It was total trial and error. You had to create the virus, test it on an in vitro or live (i.e. animal) model and see what happened. The iteration time was very slow.
RNA vaccines are a game changer:
1. They allow you to isolate concerns: You can deliver just a chunk of the virus and not the whole thing. No more fiddling around trying to hit the balance between attenuation and cross-immunogenicity because you don't have to care about the biology of the overall virus and how all its components interact [7, 8].
2. They are reprogrammable: You can deliver any RNA sequence you want and thereby manufacture virtually any viral protein you want. If the virus mutates, you can alter the RNA sequence in the vaccine to match without having to rebuild the vaccine from step one [7, 8].
3. They are easily mass produced: It's a lot easier to replicate RNA by PCR than it is to culture a virus [9].
This has big ramifications for turn-around times for developing a new vaccine or refining an existing one. It is honestly a blessing that the technology matured now, as we become increasingly global. It may end up being essential if the next pandemic involves a virus with lethality on the order of smallpox.
> I would appreciate links to literature clarifying them
Most of this is covered in Bio 101 or Immunology 101 college courses, so any introductory text should cover it. Give me a bit of time and I'll try to dig up some specific links for you.
EDIT: Here you go. Citations are provided inline. If you want a general overview, I recommend [6] and [7].
[1] https://bio.libretexts.org/Bookshelves/Introductory_and_Gene...
[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4710634/
[3] https://ocw.mit.edu/courses/hst-176-cellular-and-molecular-i...
[4] https://www.ncbi.nlm.nih.gov/books/NBK27158/
[5] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4786079/
[6] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8619084/
[7] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5906799/
[8] https://www.nature.com/articles/d41586-021-00019-w
[9] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987532/