So at what point does a peptide go from triggering an immune reaction, to being completely inert?
Off the top of my head, I can think of three possible factors:
The length of the peptide matters. Presumably, your body wouldn’t create an immune reaction to dipeptides under any circumstances. But in this case, how close are these peptides to the threshold length? If they’re well above it, then it seems this risk is still relevant. If they’re close to the threshold, then that would mitigate a lot of this risk.
The amount of the peptide matters. I’d expect that your immune system generally does not create an immune response to a single foreign peptide it detects, and that there’s a certain amount (perhaps variable between different peptides) necessary to cause a reaction. That would explain why breathing doesn’t create autoimmune issues. But in this case, we might still expect a particular partial peptide to have a significant population, especially since certain peptide-peptide bonds are weaker than others. So again, this risk is still relevant.
The peptide must be associated with some sort of damage. It’s plausible that the immune system doesn’t create a response unless it detects actual damage (irritation at the human level). In that case, the vaccine presumably works because snorting a spray is sufficiently irritating. This risk is clearly still relevant in this case.
I suspect that the actual answer is likely a combination of all three, and maybe some other stuff is relevant.
Also, I checked the white paper, and it says the partial peptides aren’t an issue, but doesn’t seem to elaborate.
Alright, so the thing that antibodies are “trained” to detect is called an epitope.
On page 23 of the white paper, it says:
VED might arise through vaccine design-induced distortion of viral epitopes, as has been
proposed to occur by formalin treatment of RSV.
a. Our preferred epitope type is synthetic peptides. Such peptides are chemically
well defined and have a high degree of structural integrity.
So distortions of the epitope can cause an autoimmune reaction, and synthetic peptides are good because they’re stable and you know exactly what you are getting. But if you have a bunch of partial peptides mixed in, then it substantially weakens this point.
Re: 3. It does seem to be true that “damage” is required. Substances which provoke an immune response are called adjuvants, and the adjuvants in this vaccine are the Chitosan and the Tripolyphosphate.
Reading the paper more closely, it says that the truncated peptides are fine because the peptides get chopped up by proteases anyway. This does make me feel a bit less worried about this, but it also implies that this would be a potential issue for purified peptides as well.
ETA:
I also did a spot-check to see at which point this would actually become an issue with the actual peptides in the vaccine using https://db.systemsbiology.net/sbeams/cgi/PeptideAtlas/Search
It seems you can generally expect length 6 sequences of peptides in radvac to be unique to the virus, while length 4 sequences of peptides from radvac are typically widespread.
So at what point does a peptide go from triggering an immune reaction, to being completely inert?
Off the top of my head, I can think of three possible factors:
The length of the peptide matters. Presumably, your body wouldn’t create an immune reaction to dipeptides under any circumstances. But in this case, how close are these peptides to the threshold length? If they’re well above it, then it seems this risk is still relevant. If they’re close to the threshold, then that would mitigate a lot of this risk.
The amount of the peptide matters. I’d expect that your immune system generally does not create an immune response to a single foreign peptide it detects, and that there’s a certain amount (perhaps variable between different peptides) necessary to cause a reaction. That would explain why breathing doesn’t create autoimmune issues. But in this case, we might still expect a particular partial peptide to have a significant population, especially since certain peptide-peptide bonds are weaker than others. So again, this risk is still relevant.
The peptide must be associated with some sort of damage. It’s plausible that the immune system doesn’t create a response unless it detects actual damage (irritation at the human level). In that case, the vaccine presumably works because snorting a spray is sufficiently irritating. This risk is clearly still relevant in this case.
I suspect that the actual answer is likely a combination of all three, and maybe some other stuff is relevant.
Also, I checked the white paper, and it says the partial peptides aren’t an issue, but doesn’t seem to elaborate.
Alright, so the thing that antibodies are “trained” to detect is called an epitope. On page 23 of the white paper, it says:
So distortions of the epitope can cause an autoimmune reaction, and synthetic peptides are good because they’re stable and you know exactly what you are getting. But if you have a bunch of partial peptides mixed in, then it substantially weakens this point.
Re: 3. It does seem to be true that “damage” is required. Substances which provoke an immune response are called adjuvants, and the adjuvants in this vaccine are the Chitosan and the Tripolyphosphate.
Reading the paper more closely, it says that the truncated peptides are fine because the peptides get chopped up by proteases anyway. This does make me feel a bit less worried about this, but it also implies that this would be a potential issue for purified peptides as well.
ETA: I also did a spot-check to see at which point this would actually become an issue with the actual peptides in the vaccine using https://db.systemsbiology.net/sbeams/cgi/PeptideAtlas/Search It seems you can generally expect length 6 sequences of peptides in radvac to be unique to the virus, while length 4 sequences of peptides from radvac are typically widespread.