4 ms·

I’m not familiar with vaccine tech. Can’t you grow the peptide of interest and package it in a traditional vaccine?

by f6v 5y ago

mlyle 5y ago
> Can’t you grow the peptide of interest and package it in a traditional vaccine? Traditional way to do this is recombinant approaches (mentioned). These are also in progress. mRNA is much quicker to iterate, though. They tried a few candidate sequences in sHIV to guide their human vaccine development. mRNA vaccines are kind of neat in the way that they create a few day long pulse of new virus-like particles showing up, to ensure the immune system gets really annoyed.
- throwaway2037 5y ago
  When you wrote <<sHIV>>, did you mean <<Simian immunodeficiency virus (SIV)>>? Ref: https://en.wikipedia.org/wiki/Simian_immunodeficiency_virus https://en.wikipedia.org/wiki/Simian_immunodeficiency_virus
  - mlyle 5y ago
    No, I meant sHIV or SHIV, which are a family of human-created viruses with SIV structure and HIV sequences within. https://journals.asm.org/doi/10.1128/JVI.00372-19 https://journals.asm.org/doi/10.1128/JVI.00372-19
siver_john 5y ago
Strictly speaking you can, and not knowing the exact reasons this approach is moved to human trials where others have not, I can only conjecture. However, the mRNA vaccine may be more stable in a way that makes it easier to make or store or for entrance into the body. Not to mention purification steps may be easier. You don't need to make this in some exotic cell line which creates a protein soup you have to purify. It may be easier on the body (less likely to develop a severe immune reaction), or it may be better at generating a sufficient immune reaction because a lot of mRNA development has gone into finding molecules that are readily taken up by the immune system regardless of cargo. These are a few reasons I can think I am sure I am missing some and there may be a stated answer out there that I have yet to search for.
- mlyle 5y ago
  > this approach is moved to human trials where others have not, I can only conjecture. Actually, a whole lot of recombinant approaches have moved to human trials (along with viral vector approaches). They early ones showed no efficacy; the newer ones we just don't know (yet). The main benefit of mRNA is iteration: you can try a whole lot of different protein mixes and see what works best in an animal model. A secondary benefit is that the sustained churning out of proteins for a few days seems to generate a much broader antibody response, making getting some of those elusive bnAbs more likely. A big problem with killed HIV vaccines and purified fragments of HIV is that growing virus in human immune cells is extraordinarily costly, and you really wouldn't want to have some live HIV leak through your purification process. So this is why we're mostly talking about other approaches to make proteins (viral vectors, recombinant DNA in bacteria and other cells, mRNA vaccines, etc)
  - siver_john 5y ago
    >Actually, a whole lot of recombinant approaches have moved to human trials (along with viral vector approaches). I should have been more clear here, I meant specifically trials of what I presume could have been attempted if the vaccine was expressed as protein instead of mRNA. But thanks for the clarification. And the mention of viral vectors which are an area I was less aware of till recently but it has been cool to see them in more places.
    - mlyle 5y ago
      > I should have been more clear here, I meant specifically trials of what I presume could have been attempted if the vaccine was expressed as protein instead of mRNA. Yes, and one vaccine approach is getting a bacterium or other virus to make a lot of a protein you're interested in, and then purifying the stuff you're interested in and forming it into a vaccine product. These are recombinant approaches. E.g. https://en.wikipedia.org/wiki/AIDSVAX https://en.wikipedia.org/wiki/AIDSVAX is exactly what you describe: a viral protein vaccine developed using recombinant approaches from e.g. Chinese hamster ovary cells https://pubmed.ncbi.nlm.nih.gov/8142140/ https://pubmed.ncbi.nlm.nih.gov/8142140/ The first was a hepatitis B vaccine developed in the 1970s where yeast cells were modified to make hepatitis B proteins. Then the HPV vaccine used the same approach, choosing proteins that would spontaneously assemble into a virus-like particle that triggers a strong immune response. Complicated proteins have to come from a living thing, in practice. So if you're going to administer a viral protein, it has to come from purifying virus that you've grown or from a recombinant approach of some kind (and growing HIV is problematic for multiple reasons).

I’m not familiar with vaccine tech. Can’t you grow the peptide of interest and package it in a traditional vaccine?

by f6v 5y ago

I’m not familiar with vaccine tech. Can’t you grow the peptide of interest and package it in a traditional vaccine?

> Can’t you grow the peptide of interest and package it in a traditional vaccine? Traditional way to do this is recombinant approaches (mentioned). These are also in progress. mRNA is much quicker to iterate, though. They tried a few candidate sequences in sHIV to guide their human vaccine development. mRNA vaccines are kind of neat in the way that they create a few day long pulse of new virus-like particles showing up, to ensure the immune system gets really annoyed.

throwaway2037 5y ago
When you wrote <<sHIV>>, did you mean <<Simian immunodeficiency virus (SIV)>>? Ref: https://en.wikipedia.org/wiki/Simian_immunodeficiency_virus https://en.wikipedia.org/wiki/Simian_immunodeficiency_virus
- mlyle 5y ago
  No, I meant sHIV or SHIV, which are a family of human-created viruses with SIV structure and HIV sequences within. https://journals.asm.org/doi/10.1128/JVI.00372-19 https://journals.asm.org/doi/10.1128/JVI.00372-19

siver_john 5y ago

Strictly speaking you can, and not knowing the exact reasons this approach is moved to human trials where others have not, I can only conjecture. However, the mRNA vaccine may be more stable in a way that makes it easier to make or store or for entrance into the body. Not to mention purification steps may be easier. You don't need to make this in some exotic cell line which creates a protein soup you have to purify. It may be easier on the body (less likely to develop a severe immune reaction), or it may be better at generating a sufficient immune reaction because a lot of mRNA development has gone into finding molecules that are readily taken up by the immune system regardless of cargo. These are a few reasons I can think I am sure I am missing some and there may be a stated answer out there that I have yet to search for.

mlyle 5y ago
> this approach is moved to human trials where others have not, I can only conjecture. Actually, a whole lot of recombinant approaches have moved to human trials (along with viral vector approaches). They early ones showed no efficacy; the newer ones we just don't know (yet). The main benefit of mRNA is iteration: you can try a whole lot of different protein mixes and see what works best in an animal model. A secondary benefit is that the sustained churning out of proteins for a few days seems to generate a much broader antibody response, making getting some of those elusive bnAbs more likely. A big problem with killed HIV vaccines and purified fragments of HIV is that growing virus in human immune cells is extraordinarily costly, and you really wouldn't want to have some live HIV leak through your purification process. So this is why we're mostly talking about other approaches to make proteins (viral vectors, recombinant DNA in bacteria and other cells, mRNA vaccines, etc)
- siver_john 5y ago
  >Actually, a whole lot of recombinant approaches have moved to human trials (along with viral vector approaches). I should have been more clear here, I meant specifically trials of what I presume could have been attempted if the vaccine was expressed as protein instead of mRNA. But thanks for the clarification. And the mention of viral vectors which are an area I was less aware of till recently but it has been cool to see them in more places.
  - mlyle 5y ago
    > I should have been more clear here, I meant specifically trials of what I presume could have been attempted if the vaccine was expressed as protein instead of mRNA. Yes, and one vaccine approach is getting a bacterium or other virus to make a lot of a protein you're interested in, and then purifying the stuff you're interested in and forming it into a vaccine product. These are recombinant approaches. E.g. https://en.wikipedia.org/wiki/AIDSVAX https://en.wikipedia.org/wiki/AIDSVAX is exactly what you describe: a viral protein vaccine developed using recombinant approaches from e.g. Chinese hamster ovary cells https://pubmed.ncbi.nlm.nih.gov/8142140/ https://pubmed.ncbi.nlm.nih.gov/8142140/ The first was a hepatitis B vaccine developed in the 1970s where yeast cells were modified to make hepatitis B proteins. Then the HPV vaccine used the same approach, choosing proteins that would spontaneously assemble into a virus-like particle that triggers a strong immune response. Complicated proteins have to come from a living thing, in practice. So if you're going to administer a viral protein, it has to come from purifying virus that you've grown or from a recombinant approach of some kind (and growing HIV is problematic for multiple reasons).