5 ms·

I was reading about the mRNA approach recently and wondered why not just inject the spike protein itself? Why have our body make the protein instead? Does anyon

I was reading about the mRNA approach recently and wondered why not just inject the spike protein itself? Why have our body make the protein instead? Does anyone here know? It's interesting to see that both approaches yield such good results, and the end result, triggering immune response to the spike, seems about the same.

detaro 5y ago
That's what the Novavax vaccine does, but it's still in testing and approval stages (although the trials results for now look like it works fine). As far as I understand, part of the problem is finding a way to produce the correct protein efficiently.
baybal2 5y ago
> Why have our body make the protein instead? Not so easy to make enough, and handle it just like every isolated biological molecule?
- danzk 5y ago
  It's expensive and difficult to scale when you're trying to make millions of doses.
superkuh 5y ago
It boils down to the mRNA process being faster and more of a sure thing for a novel virus. I hope there are eventually many more effective protein based vaccines approved. The problem with expressing your protein in some animal cell is that often times there are sugars that cells add to proteins and they differ by lifeform type. So the protein will end up shaped different in a yeast than in a animal cell. Additionally, growing in a third party host lifeform often leads to situations where you can't get it to grow in the host anymore because the virus changes.
- baybal2 5y ago
  The sure thing for a novel virus, as I understood, is an inactivated vaccine. For everything else, you are never sure if the biotech tricks, with all their intricacies, will work in that individual case.
  - superkuh 5y ago
    Well, you're sure to get something with an inactivated viral particle. But you're not sure to get a usefully efficient protection from exposure to it. The problem with inactivated viral particles is the inactivation process, neccessarily, breaks the proteins and cause them to be liable to take up non-realistic shapes. When your immune system trains on the non-realistic shape the antibodies don't neutralize as well. See the sinovac inactivated sars-cov-2 vaccine for an example of this type of vaccine not working out (ie, <50% efficient).
danzk 5y ago
There's nothing medically wrong with the approach, however protein based pharmaceuticals are slow and expensive to manufacture, which isn't ideal when you are trying to vaccinate millions of people, cheaply. To manufacture a protein you need to create a genetically modified bacteria that contains the DNA for that protein, grow a large batch of this bacteria (which can be difficult at scale), and then break open the bacteria filter out all the other proteins and just keep the one you want. This is why the mRNA is so elegant, it gives your body the instructions to manufacture the protein itself.
- noveltyaccount 5y ago
  Great answer, thank you!
- maxerickson 5y ago
  The mRNA vaccines are sliced out of plasmids grown in bacteria (as DNA which is then transcribed into RNA). https://www.nytimes.com/interactive/2021/health/pfizer-coronavirus-vaccine.html https://www.nytimes.com/interactive/2021/health/pfizer-coron...
  - samus 5y ago
    The nice thing about mRNA vaccines is that this has to be done only infrequently. The crucial point is that this DNA should be able to be transcribed into many mRNA molecules. Else, I have no idea how the one plant where the DNA is grown could supply the whole world.
    - maxerickson 5y ago
      The article I link implies they use each bottle of DNA in a day (not each batch, a bottle from the batch that they thaw for use). I imagine it's a quality control thing.
occamrazor 5y ago
The short answer is that proteins are too complex to manufacture, and it’s more effective to instruct your body (which has a lot of protein manufacturing capacity) to produce the protein. There are attempts to use peptides. They are much shorter chains of amino acids , they are easy to produce, but it’s difficult to find peptides that reproduce the external structure of the virus. There is an experimental Russian vaccine based on peptides, but the results haven’t been published yet.
tzs 5y ago
When the mRNA vaccine is injected into your arm muscles some of it ends up in the cells of the muscle and some of it ends up in the intercellular fluid. The latter drains via the lymphatic system and will end up in the lymph nodes in the upper body on the side you got the shot it (which is a good place to end up since the lymph nodes are a major site for immune response). Some will end up in the blood, and so might end up elsewhere. Whatever cells it ends up in, the mRNA has them make the spike protein. That spike protein ends up attached to the outside surface of the cell that made it and it stays there [1]. If you injected spike protein directly, it could end up anywhere. I don't know if this has been tested in humans yet, but there has been research in mice where spike protein injected damaged their lungs [2]. [1] https://blogs.sciencemag.org/pipeline/archives/2021/05/04/spike-protein-behavior https://blogs.sciencemag.org/pipeline/archives/2021/05/04/sp... [2] https://www.contagionlive.com/view/spike-protein-of-sars-cov-2-virus-alone-can-cause-damage-to-lungs https://www.contagionlive.com/view/spike-protein-of-sars-cov...
- maxerickson 5y ago
  Spike protein moving around free has been proposed as a potential source of the problems with the adenovirus vector vaccines. (errors in the transcription process end up preventing it from properly attaching to the cell)
- alister 5y ago
  > will end up in the lymph nodes in the upper body on the side you got the shot in (which is a good place to end up since the lymph nodes are a major site for immune response) Would it be worthwhile to get the first shot in the left shoulder and the second in the right shouder (or vice versa) so you have lymph node immune response from both sides of the upper body?
- lugged 5y ago
  Aren't spike proteins moving freely, specifically, concentrating in the ovaries what is concerning Robert Malone? [1] [1] https://bit.ly/2Td5gWz https://bit.ly/2Td5gWz E: curious why downvotes, am I misinformed?
  - 5y ago
peytn 5y ago
Practical reason is that life sci VCs want to fund “platforms” in recent years, and mRNA can be pitched as a “platform,” so that’s what got funded.
esyir 5y ago
One of the big reasons is that mrna is also much easier to manufacture than proteins. If I wanted to, I could pay for a arbitrary mrna sequence delivered to be within the week. Its basically been commoditized. Conversely, getting a protein at scale requires the engineering of an organism to synthesise the protein of interest. This results in increased delay in manufacture.

detaro 5y ago

That's what the Novavax vaccine does, but it's still in testing and approval stages (although the trials results for now look like it works fine). As far as I understand, part of the problem is finding a way to produce the correct protein efficiently.

baybal2 5y ago

> Why have our body make the protein instead? Not so easy to make enough, and handle it just like every isolated biological molecule?

danzk 5y ago
It's expensive and difficult to scale when you're trying to make millions of doses.

superkuh 5y ago

It boils down to the mRNA process being faster and more of a sure thing for a novel virus. I hope there are eventually many more effective protein based vaccines approved. The problem with expressing your protein in some animal cell is that often times there are sugars that cells add to proteins and they differ by lifeform type. So the protein will end up shaped different in a yeast than in a animal cell. Additionally, growing in a third party host lifeform often leads to situations where you can't get it to grow in the host anymore because the virus changes.

baybal2 5y ago
The sure thing for a novel virus, as I understood, is an inactivated vaccine. For everything else, you are never sure if the biotech tricks, with all their intricacies, will work in that individual case.
- superkuh 5y ago
  Well, you're sure to get something with an inactivated viral particle. But you're not sure to get a usefully efficient protection from exposure to it. The problem with inactivated viral particles is the inactivation process, neccessarily, breaks the proteins and cause them to be liable to take up non-realistic shapes. When your immune system trains on the non-realistic shape the antibodies don't neutralize as well. See the sinovac inactivated sars-cov-2 vaccine for an example of this type of vaccine not working out (ie, <50% efficient).

danzk 5y ago

There's nothing medically wrong with the approach, however protein based pharmaceuticals are slow and expensive to manufacture, which isn't ideal when you are trying to vaccinate millions of people, cheaply. To manufacture a protein you need to create a genetically modified bacteria that contains the DNA for that protein, grow a large batch of this bacteria (which can be difficult at scale), and then break open the bacteria filter out all the other proteins and just keep the one you want. This is why the mRNA is so elegant, it gives your body the instructions to manufacture the protein itself.

noveltyaccount 5y ago
Great answer, thank you!
maxerickson 5y ago
The mRNA vaccines are sliced out of plasmids grown in bacteria (as DNA which is then transcribed into RNA). https://www.nytimes.com/interactive/2021/health/pfizer-coronavirus-vaccine.html https://www.nytimes.com/interactive/2021/health/pfizer-coron...
- samus 5y ago
  The nice thing about mRNA vaccines is that this has to be done only infrequently. The crucial point is that this DNA should be able to be transcribed into many mRNA molecules. Else, I have no idea how the one plant where the DNA is grown could supply the whole world.
  - maxerickson 5y ago
    The article I link implies they use each bottle of DNA in a day (not each batch, a bottle from the batch that they thaw for use). I imagine it's a quality control thing.

occamrazor 5y ago

The short answer is that proteins are too complex to manufacture, and it’s more effective to instruct your body (which has a lot of protein manufacturing capacity) to produce the protein. There are attempts to use peptides. They are much shorter chains of amino acids , they are easy to produce, but it’s difficult to find peptides that reproduce the external structure of the virus. There is an experimental Russian vaccine based on peptides, but the results haven’t been published yet.

tzs 5y ago

When the mRNA vaccine is injected into your arm muscles some of it ends up in the cells of the muscle and some of it ends up in the intercellular fluid. The latter drains via the lymphatic system and will end up in the lymph nodes in the upper body on the side you got the shot it (which is a good place to end up since the lymph nodes are a major site for immune response). Some will end up in the blood, and so might end up elsewhere. Whatever cells it ends up in, the mRNA has them make the spike protein. That spike protein ends up attached to the outside surface of the cell that made it and it stays there [1]. If you injected spike protein directly, it could end up anywhere. I don't know if this has been tested in humans yet, but there has been research in mice where spike protein injected damaged their lungs [2]. [1] https://blogs.sciencemag.org/pipeline/archives/2021/05/04/spike-protein-behavior https://blogs.sciencemag.org/pipeline/archives/2021/05/04/sp... [2] https://www.contagionlive.com/view/spike-protein-of-sars-cov-2-virus-alone-can-cause-damage-to-lungs https://www.contagionlive.com/view/spike-protein-of-sars-cov...

maxerickson 5y ago
Spike protein moving around free has been proposed as a potential source of the problems with the adenovirus vector vaccines. (errors in the transcription process end up preventing it from properly attaching to the cell)
alister 5y ago
> will end up in the lymph nodes in the upper body on the side you got the shot in (which is a good place to end up since the lymph nodes are a major site for immune response) Would it be worthwhile to get the first shot in the left shoulder and the second in the right shouder (or vice versa) so you have lymph node immune response from both sides of the upper body?
lugged 5y ago
Aren't spike proteins moving freely, specifically, concentrating in the ovaries what is concerning Robert Malone? [1] [1] https://bit.ly/2Td5gWz https://bit.ly/2Td5gWz E: curious why downvotes, am I misinformed?
- 5y ago

peytn 5y ago

Practical reason is that life sci VCs want to fund “platforms” in recent years, and mRNA can be pitched as a “platform,” so that’s what got funded.

esyir 5y ago

One of the big reasons is that mrna is also much easier to manufacture than proteins. If I wanted to, I could pay for a arbitrary mrna sequence delivered to be within the week. Its basically been commoditized. Conversely, getting a protein at scale requires the engineering of an organism to synthesise the protein of interest. This results in increased delay in manufacture.