9 ms·

Does the fact that Covid-19 is an RNA virus make it easier to target with an mRNA-vaccine? Could this technology also be used to target a DNA virus as well?

rolph 6y ago
in short, yes; and yes. the limitation is an understanding of the virus+host interaction at the level of molecular structure and function. when you have the amino acid sequence of a protien that triggers the immune system you can work backward and derive an mRNA that would be responsible for coding the protien. there are multiple layers of complexity in getting from stage 1 to end product but this is a quick simple layout. DNA virus has some extra tricks compared to RNA virus but the core concept is the same for both.
- bilal4hmed 6y ago
  Would such a technique help an immune compromised or suppressed person ?
  - rolph 6y ago
    an immune compromised person may require larger repeated doses, or a different/concurrent strategy such as antibody infusion
  - wittyreference 6y ago
    The vaccine in this instance is all about delivering a target to the immune system's sentries. If those sentries are defective, or if the hitmen the sentries need to alert are defective, there's nothing this vaccine can do to change that. "Immune compromise" is generally used as a blanket term, but in many people there are specific immune deficiencies, which may or may not factor into the pathway being targeted here. For instance, natalizumab screws with immune cells' translocation across membranes, and shouldn't play a role in responding to a vaccine (I mean, if it wasn't off the market anyway). If it's a general immune dysfunction (cancer, diabetes), they will see some benefit, but it will be much reduced - specifically because both responding to the vaccine, and responding to the virus post-vaccination, require the activity of the immune system. What this means precisely will vary with the degree and nature of the immune dysfunction: some folks might see some antibody response, and benefit from repeat dosing. Others might fail to seroconvert altogether, in which case it is what it is.
- jbaudanza 6y ago
  I see, thanks for the reply! I was thinking that maybe because Covid is an RNA virus, there would be a shortcut to getting the mRNA sequence for creating the spike protein. The scientists could peek at the RNA in the actual virus, recognize the spike protein, and put that in the vaccine. Whereas with a DNA virus, it would require extra work. But from your answer, it sounds like that's not what they do? Or, maybe they could do that but it's not any easier than working backwards from the amino acid sequence. This stuff is all very interesting!
  - rolph 6y ago
    the short cut is that DNA virus has a further layer of code utilization , the DNA must be read out and transcribed to mRNA, then translated to protien. there is an extra step in there, but you can still use a synthetic mRNA to create a protien specific to putative antigens decorating the surface of the DNA virus, or of the infected cell, or both if your rich and want to make sure. a DNA virus must be understood somewhat to find the reading frame for the protien you need, this is the case for RNA virus as well however RNA virus are limited in size due to the instability of RNA, this means less kruft to wade through until you find the FOO
- raphaelj 6y ago
  Is there a reason they don't create the protein in Vito and them inject it as a vaccine? I would imagine they could use in Vito cells to generate a lot of spike proteins. Are they using mRNA because it's easier to manufacture? Or is the protein too instable?
  - rolph 6y ago
    the protien, and the mRNA would be instantly degraded outside the cell. the liposomal capsule holding the mRNA has been engineered to deliver the mRNA to the cell and fuse with it delivering the mRNA confoundingly the mRNA is fragile thus the ultracold dryice freezer required for holding. the protien is stable on its own, but will be destroyed by exocytic proteases unless shielded by insertion into a membrane
nicwilson 6y ago
No. Yes. This approach is like sneaking in blueprints to a factory (cell) that makes (proteins using mRNA) whatever it has blueprints for, and gets inspectors that come around occasionally (immune surveillance), or very frequently under active infection, looking for contraband. When the body start producing this foreign proteins in the presence of something to trigger the immune system (called an adjuvant which all vaccines use to make the body recognise as bad and not harmless/irrelevant) the immune system starts producing a response against that.
- rolph 6y ago
  adjuvent is not neccesary for immune response, it is nessecary for spreading out the antigen producing character among more doses, rather than using a concentration of mRNA that in itself produces enough protien to induce immune response
  - nicwilson 6y ago
    What? > adjuvent [sic] is not neccesary[sic] for immune response, Completely false. Unless the immune system has been exposed to something similar before (e.g. SARS/MERS n.b. made up example I have no idea if the spikes of SARS or MERS are molecularly similar enough), no adjuvant means situation normal for the immune system. If there is nothing to signal to the immune system that this new antigen is bad then it will treat it as neutral suppressing any vaccine response, which is worse that if the vaccine had not been delivered at all. >is nessecary[sic] for spreading out the antigen producing character among more doses the point of booster shots is to ensure that antibodies are maintained at sufficient levels to fight off a real infection. If a response has been established, i guess adjuvants are not as necessary? (did biomed, but not a vaccine researcher) I have no idea if they are included or not for boosters. > rather than using a concentration of mRNA that in itself produces enough protien[sic] to induce immune response A high concentration won't do shit if the immune system doesn't have anything to activate it, it will just see a high concentration of irrelevant new, i.e. foreign protein.
    - rolph 6y ago

rolph 6y ago

in short, yes; and yes. the limitation is an understanding of the virus+host interaction at the level of molecular structure and function. when you have the amino acid sequence of a protien that triggers the immune system you can work backward and derive an mRNA that would be responsible for coding the protien. there are multiple layers of complexity in getting from stage 1 to end product but this is a quick simple layout. DNA virus has some extra tricks compared to RNA virus but the core concept is the same for both.

bilal4hmed 6y ago
Would such a technique help an immune compromised or suppressed person ?
- rolph 6y ago
  an immune compromised person may require larger repeated doses, or a different/concurrent strategy such as antibody infusion
- wittyreference 6y ago
  The vaccine in this instance is all about delivering a target to the immune system's sentries. If those sentries are defective, or if the hitmen the sentries need to alert are defective, there's nothing this vaccine can do to change that. "Immune compromise" is generally used as a blanket term, but in many people there are specific immune deficiencies, which may or may not factor into the pathway being targeted here. For instance, natalizumab screws with immune cells' translocation across membranes, and shouldn't play a role in responding to a vaccine (I mean, if it wasn't off the market anyway). If it's a general immune dysfunction (cancer, diabetes), they will see some benefit, but it will be much reduced - specifically because both responding to the vaccine, and responding to the virus post-vaccination, require the activity of the immune system. What this means precisely will vary with the degree and nature of the immune dysfunction: some folks might see some antibody response, and benefit from repeat dosing. Others might fail to seroconvert altogether, in which case it is what it is.
jbaudanza 6y ago
I see, thanks for the reply! I was thinking that maybe because Covid is an RNA virus, there would be a shortcut to getting the mRNA sequence for creating the spike protein. The scientists could peek at the RNA in the actual virus, recognize the spike protein, and put that in the vaccine. Whereas with a DNA virus, it would require extra work. But from your answer, it sounds like that's not what they do? Or, maybe they could do that but it's not any easier than working backwards from the amino acid sequence. This stuff is all very interesting!
- rolph 6y ago
  the short cut is that DNA virus has a further layer of code utilization , the DNA must be read out and transcribed to mRNA, then translated to protien. there is an extra step in there, but you can still use a synthetic mRNA to create a protien specific to putative antigens decorating the surface of the DNA virus, or of the infected cell, or both if your rich and want to make sure. a DNA virus must be understood somewhat to find the reading frame for the protien you need, this is the case for RNA virus as well however RNA virus are limited in size due to the instability of RNA, this means less kruft to wade through until you find the FOO
raphaelj 6y ago
Is there a reason they don't create the protein in Vito and them inject it as a vaccine? I would imagine they could use in Vito cells to generate a lot of spike proteins. Are they using mRNA because it's easier to manufacture? Or is the protein too instable?
- rolph 6y ago
  the protien, and the mRNA would be instantly degraded outside the cell. the liposomal capsule holding the mRNA has been engineered to deliver the mRNA to the cell and fuse with it delivering the mRNA confoundingly the mRNA is fragile thus the ultracold dryice freezer required for holding. the protien is stable on its own, but will be destroyed by exocytic proteases unless shielded by insertion into a membrane

nicwilson 6y ago

No. Yes. This approach is like sneaking in blueprints to a factory (cell) that makes (proteins using mRNA) whatever it has blueprints for, and gets inspectors that come around occasionally (immune surveillance), or very frequently under active infection, looking for contraband. When the body start producing this foreign proteins in the presence of something to trigger the immune system (called an adjuvant which all vaccines use to make the body recognise as bad and not harmless/irrelevant) the immune system starts producing a response against that.

rolph 6y ago
adjuvent is not neccesary for immune response, it is nessecary for spreading out the antigen producing character among more doses, rather than using a concentration of mRNA that in itself produces enough protien to induce immune response
- nicwilson 6y ago
  What? > adjuvent [sic] is not neccesary[sic] for immune response, Completely false. Unless the immune system has been exposed to something similar before (e.g. SARS/MERS n.b. made up example I have no idea if the spikes of SARS or MERS are molecularly similar enough), no adjuvant means situation normal for the immune system. If there is nothing to signal to the immune system that this new antigen is bad then it will treat it as neutral suppressing any vaccine response, which is worse that if the vaccine had not been delivered at all. >is nessecary[sic] for spreading out the antigen producing character among more doses the point of booster shots is to ensure that antibodies are maintained at sufficient levels to fight off a real infection. If a response has been established, i guess adjuvants are not as necessary? (did biomed, but not a vaccine researcher) I have no idea if they are included or not for boosters. > rather than using a concentration of mRNA that in itself produces enough protien[sic] to induce immune response A high concentration won't do shit if the immune system doesn't have anything to activate it, it will just see a high concentration of irrelevant new, i.e. foreign protein.
  - rolph 6y ago