6 ms·

In my understanding from having read the literature over time, the RNA vaccine was, as far as I can tell at least, sloppy thinking. Someone thought that setting

In my understanding from having read the literature over time, the RNA vaccine was, as far as I can tell at least, sloppy thinking. Someone thought that setting up a permanent factory in the body for spike proteins was a bright idea. 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 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? Disclosure: I am vaccinated, for what it's worth, with the Novavax (Nuvaxovid), which is in my understanding just a one time dose of spike proteins and an adjuvant, to train the body to fight the virus. I may have a wrong understanding, but, if I'm right, 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. -edit- If I am wrong on those points, I would appreciate links to literature clarifying them. I'm not advocating an anti-vaccination position.

Gordonjcp 4y ago
> I may have a wrong understanding, but, if I'm right, 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. Because none of that is actually happening, and RNA vaccines aren't causing the kind of problems the hysterical moon-howlers are coming up with. Admittedly they're a relatively new technology, having only been in use for about 50 years as opposed to attenuated viruses which have been in use for about 250 years.
- superchroma 4y ago
  So, which part? The debatable claims are: 1) that RNA vaccines tell the body to make spike proteins and it will do this indefinitely, 2) the spike protein is not an indefinitely relevant marker by which to eliminate COVID, particularly as it evolves and 3) spike proteins aren't great to have around in the body, (yes I've heard they get cleaned up fairly promptly via mechanisms) I'm not saying it's nanomachines or anything, and I'm not making a fuss about how long they've been around; I didn't mention it. I got vaccinated. I'm on the team. But if these planks of my understanding aren't sound I'm interested. Fundamentally, I want to understand how these things work. The protein based vaccine is uncomplicated, I understand the basics of the mechnism, the RNA one leaves lingering questions that I can't source answers to. I'm an educated professional, and I've read some papers and watched a lot of the news on the matter on here and other platforms, and that hasn't settled my questions.
  - Turing_Machine 4y ago
    > that RNA vaccines tell the body to make spike proteins Correct. > and it will do this indefinitely Incorrect.
- miles 4y ago
  [flagged]
Calavar 4y ago
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]. [1] https://bio.libretexts.org/Bookshelves/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/15%3A_Genes_and_Proteins/15.02%3A_The_Genetic_Code_-_The_Central_Dogma-_DNA_Encodes_RNA_and_RNA_Encodes_Protein https://bio.libretexts.org/Bookshelves/Introductory_and_Gene... [2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4710634/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4710634/ [3] https://ocw.mit.edu/courses/hst-176-cellular-and-molecular-immunology-fall-2005/resources/antigen_rec/ https://ocw.mit.edu/courses/hst-176-cellular-and-molecular-i... [4] https://www.ncbi.nlm.nih.gov/books/NBK27158/ https://www.ncbi.nlm.nih.gov/books/NBK27158/ [5] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4786079/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4786079/ [6] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8619084/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8619084/ [7] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5906799/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5906799/ [8] https://www.nature.com/articles/d41586-021-00019-w https://www.nature.com/articles/d41586-021-00019-w [9] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987532/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987532/
Turing_Machine 4y ago
> Someone thought that setting up a permanent factory in the body for spike proteins That is absolutely not the case. mRNA has a very limited lifespan in the body. It does not become a "permanent factory".

Gordonjcp 4y ago

> I may have a wrong understanding, but, if I'm right, 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. Because none of that is actually happening, and RNA vaccines aren't causing the kind of problems the hysterical moon-howlers are coming up with. Admittedly they're a relatively new technology, having only been in use for about 50 years as opposed to attenuated viruses which have been in use for about 250 years.

superchroma 4y ago
So, which part? The debatable claims are: 1) that RNA vaccines tell the body to make spike proteins and it will do this indefinitely, 2) the spike protein is not an indefinitely relevant marker by which to eliminate COVID, particularly as it evolves and 3) spike proteins aren't great to have around in the body, (yes I've heard they get cleaned up fairly promptly via mechanisms) I'm not saying it's nanomachines or anything, and I'm not making a fuss about how long they've been around; I didn't mention it. I got vaccinated. I'm on the team. But if these planks of my understanding aren't sound I'm interested. Fundamentally, I want to understand how these things work. The protein based vaccine is uncomplicated, I understand the basics of the mechnism, the RNA one leaves lingering questions that I can't source answers to. I'm an educated professional, and I've read some papers and watched a lot of the news on the matter on here and other platforms, and that hasn't settled my questions.
- Turing_Machine 4y ago
  > that RNA vaccines tell the body to make spike proteins Correct. > and it will do this indefinitely Incorrect.
miles 4y ago
[flagged]

Calavar 4y ago

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]. [1] https://bio.libretexts.org/Bookshelves/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/15%3A_Genes_and_Proteins/15.02%3A_The_Genetic_Code_-_The_Central_Dogma-_DNA_Encodes_RNA_and_RNA_Encodes_Protein https://bio.libretexts.org/Bookshelves/Introductory_and_Gene... [2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4710634/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4710634/ [3] https://ocw.mit.edu/courses/hst-176-cellular-and-molecular-immunology-fall-2005/resources/antigen_rec/ https://ocw.mit.edu/courses/hst-176-cellular-and-molecular-i... [4] https://www.ncbi.nlm.nih.gov/books/NBK27158/ https://www.ncbi.nlm.nih.gov/books/NBK27158/ [5] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4786079/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4786079/ [6] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8619084/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8619084/ [7] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5906799/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5906799/ [8] https://www.nature.com/articles/d41586-021-00019-w https://www.nature.com/articles/d41586-021-00019-w [9] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987532/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987532/

Turing_Machine 4y ago

> Someone thought that setting up a permanent factory in the body for spike proteins That is absolutely not the case. mRNA has a very limited lifespan in the body. It does not become a "permanent factory".