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On face value, it sounds less risky than the standard vaccine development route, which may involve introducing immortalized (i.e. cancerous) cells or artificial

On face value, it sounds less risky than the standard vaccine development route, which may involve introducing immortalized (i.e. cancerous) cells or artificially stimulating an immune response with known toxins (adjuvants). I still have questions about the mRNA vaccine concept. Maybe some well-informed HNer can shed light? 1. If the goal is to get the desired protein inside the patient's body, why is injecting mRNA that produces the protein more effective than simply introducing the protein itself? 2. How does the patient's immune system know to treat this protein as unwanted if it's being produced by the body's own cells? 3. How do vaccine developers avoid creating an over-active immune response in the patient (i.e. an allergy)?

fabian2k 6y ago
Adjuvants are not toxic, they're simply known to enhance the immune system response (so they are something that indicates danger to the immune system). The immune system is incredibly dangerous and destructive, and you really don't want to trigger it without reason. So injecting something unknown might not be enough to get the immune system fully alarmed, that's why some vaccines add adjuvants to produce a stronger response. RNA can be an adjuvant by itself, as it's also a typical component of viruses and the immune system reacts to that. So the trick really is to design the RNA and the delivery system so that it produces an immune response of the right magnitude. Too weak and it doesn't work, too strong and it's harmful. Antibodies that bind to your own proteins are filtered in an earlier stage in antibody production. Real viral proteins are also produced by your own cells, so that is never a factor by which you could distinguish friend from foe.
- tboyd47 6y ago
  Is aluminum not toxic?
raducu 6y ago
1. I guess for smaller batches it is easier to develop the mRNA. Otherwise, we would have monoclonal antibodies and not a vaccine(the vaccine has other benefits, it trains the T-cells and the B cells remain dormant even after no abtibodies are detected in the blood). 2. The imune system knows all your protein already, t cells are evolved in the thymus gland, if they attack anything "self", they get destriyed.
gus_massa 6y ago
> which may involve introducing immortalized (i.e. cancerous) cells Which one? I don't remember any vaccine that injects immortalized cells.
- tboyd47 6y ago
  Feel free to correct if I'm misinterpreting: https://en.wikipedia.org/wiki/Use_of_fetal_tissue_in_vaccine_development#Background https://en.wikipedia.org/wiki/Use_of_fetal_tissue_in_vaccine...
  - rolph 6y ago
    the vaccine doesnt contain fetal cells, in the case you are providing the vaccine is an attenuated virus approach. the cells are used to manufacture quantities of the virus in an extremely weakened form. This gives a chance for the immune systemto mount a response before the pathogen initiates systemic disease response. the cells in question are not freshly harvested from a foetus, the progenitor cells are harvested and kept in continual culture for use. the reason immortalized cells are used is to escape the "expiry date" of a normal cell. >>Some vaccines currently available were developed using cell strains cultured from two fetuses aborted for other purposes in the 1960s.[6]<< i lifted this link from the wiki page provided: https://en.wikipedia.org/wiki/Immortalised_cell_line https://en.wikipedia.org/wiki/Immortalised_cell_line
    - tboyd47 6y ago
      Thanks.
therein 6y ago
I have been asking the very same questions, especially the (2). So far, nobody has been able to provide a satisfying answer.
- fabian2k 6y ago
  The simplistic answer is that the immune system tries out new antigen-detecting cells in a safe environment before letting them run around with a loaded gun. Any cell that activates in that safe environment is destroyed, as it recognized one of your own antigens. The other mechanism is that the immune system doesn't react only to foreign antigens, there also needs to be some general activation of the immune system in that area for a real response. The full answer is that this is really, really complex like pretty much everything involving the immune system. And auto-immune diseases indicate that the immune system doesn't always get this right.
  - tboyd47 6y ago
    How is that general activation achieved in the case of this mRNA vaccine and the others that will surely follow?
    - fabian2k 6y ago
      RNA itself is suspicious because it's a major component of many viruses. So some kinds of RNA will activate the innate immune system strongly.
      - tboyd47 6y ago
        That's really interesting and confirmed with some light searching. Thanks!
- rolph 6y ago
  there is a system homologous to machine learning 2factor authentication. in very loose terms both keys must be presented while the immune system is in training, the instances where protiens are expressed with out cell surface recognition molecules in proximity are invalid thus foriegn, and memory immunity to this "failed login" is maintained. when both factors [protien plus recognition] are present constituitively over the course of development the immune response is squelched. this is known as central tolerance. https://en.wikipedia.org/wiki/Central_tolerance https://en.wikipedia.org/wiki/Central_tolerance
BurningFrog 6y ago
> 2. How does the patient's immune system know to treat this protein as unwanted if it's being produced by the body's own cells The immune system can't know who produced a certain molecule.
gostsamo 6y ago
1. A single rna can produce multiple times the protein, because it is like the proverb about giving someone fish and teaching them fishing. 2. Someone already said, but a protein has no marker saying "local produce". It is either allowed or not and the body reacts or not when detecting it. 3. They hope. Measure the dosage and adjust. As it was reported, some people getting the vaccine have an allergic reaction, but hopefully it will be rare and under control. So far there are only a few cases reported.
- deleted 6y ago
  [deleted]

fabian2k 6y ago

Adjuvants are not toxic, they're simply known to enhance the immune system response (so they are something that indicates danger to the immune system). The immune system is incredibly dangerous and destructive, and you really don't want to trigger it without reason. So injecting something unknown might not be enough to get the immune system fully alarmed, that's why some vaccines add adjuvants to produce a stronger response. RNA can be an adjuvant by itself, as it's also a typical component of viruses and the immune system reacts to that. So the trick really is to design the RNA and the delivery system so that it produces an immune response of the right magnitude. Too weak and it doesn't work, too strong and it's harmful. Antibodies that bind to your own proteins are filtered in an earlier stage in antibody production. Real viral proteins are also produced by your own cells, so that is never a factor by which you could distinguish friend from foe.

tboyd47 6y ago
Is aluminum not toxic?

raducu 6y ago

1. I guess for smaller batches it is easier to develop the mRNA. Otherwise, we would have monoclonal antibodies and not a vaccine(the vaccine has other benefits, it trains the T-cells and the B cells remain dormant even after no abtibodies are detected in the blood). 2. The imune system knows all your protein already, t cells are evolved in the thymus gland, if they attack anything "self", they get destriyed.

gus_massa 6y ago

> which may involve introducing immortalized (i.e. cancerous) cells Which one? I don't remember any vaccine that injects immortalized cells.

tboyd47 6y ago
Feel free to correct if I'm misinterpreting: https://en.wikipedia.org/wiki/Use_of_fetal_tissue_in_vaccine_development#Background https://en.wikipedia.org/wiki/Use_of_fetal_tissue_in_vaccine...
- rolph 6y ago
  the vaccine doesnt contain fetal cells, in the case you are providing the vaccine is an attenuated virus approach. the cells are used to manufacture quantities of the virus in an extremely weakened form. This gives a chance for the immune systemto mount a response before the pathogen initiates systemic disease response. the cells in question are not freshly harvested from a foetus, the progenitor cells are harvested and kept in continual culture for use. the reason immortalized cells are used is to escape the "expiry date" of a normal cell. >>Some vaccines currently available were developed using cell strains cultured from two fetuses aborted for other purposes in the 1960s.[6]<< i lifted this link from the wiki page provided: https://en.wikipedia.org/wiki/Immortalised_cell_line https://en.wikipedia.org/wiki/Immortalised_cell_line
  - tboyd47 6y ago
    Thanks.

therein 6y ago

I have been asking the very same questions, especially the (2). So far, nobody has been able to provide a satisfying answer.

fabian2k 6y ago
The simplistic answer is that the immune system tries out new antigen-detecting cells in a safe environment before letting them run around with a loaded gun. Any cell that activates in that safe environment is destroyed, as it recognized one of your own antigens. The other mechanism is that the immune system doesn't react only to foreign antigens, there also needs to be some general activation of the immune system in that area for a real response. The full answer is that this is really, really complex like pretty much everything involving the immune system. And auto-immune diseases indicate that the immune system doesn't always get this right.
- tboyd47 6y ago
  How is that general activation achieved in the case of this mRNA vaccine and the others that will surely follow?
  - fabian2k 6y ago
    RNA itself is suspicious because it's a major component of many viruses. So some kinds of RNA will activate the innate immune system strongly.
    - tboyd47 6y ago
      That's really interesting and confirmed with some light searching. Thanks!
rolph 6y ago
there is a system homologous to machine learning 2factor authentication. in very loose terms both keys must be presented while the immune system is in training, the instances where protiens are expressed with out cell surface recognition molecules in proximity are invalid thus foriegn, and memory immunity to this "failed login" is maintained. when both factors [protien plus recognition] are present constituitively over the course of development the immune response is squelched. this is known as central tolerance. https://en.wikipedia.org/wiki/Central_tolerance https://en.wikipedia.org/wiki/Central_tolerance

BurningFrog 6y ago

> 2. How does the patient's immune system know to treat this protein as unwanted if it's being produced by the body's own cells The immune system can't know who produced a certain molecule.

gostsamo 6y ago

1. A single rna can produce multiple times the protein, because it is like the proverb about giving someone fish and teaching them fishing. 2. Someone already said, but a protein has no marker saying "local produce". It is either allowed or not and the body reacts or not when detecting it. 3. They hope. Measure the dosage and adjust. As it was reported, some people getting the vaccine have an allergic reaction, but hopefully it will be rare and under control. So far there are only a few cases reported.

deleted 6y ago
[deleted]