Spike 802-823cir: FSQ c LPDPSKPSKRSF c EDLLF ( Cys4, Cys17 disulfide) IN TESTING, vaccine Generations 5, 6, 7, 8. 9 To preserve the loop structure present in the native conformation, we substituted cysteines for amino acids 4 (Ile>Cys) and 17 (Ile>Cys).
They perform the substitution to keep the shape that our immune system is looking for by recreating a disulfide bond that to form a loop with the same sequence the B-cells are targeting in the virus.
While I agree their expression was “potentially beneficial” (or close) it seems clear to me the point was our B-cells are bonding to that loop and if there are not other aspect in the larger peptide that lead the cell to that site for bonding, construction the loop via the disulfide bond they introduce logically should result in triggering an immune response.
I’m not sure why they would need to provide some type of citation for this, much less that they would even have a source for this specific application.
The argument about the substition of the amino acids looks to me like it rests completely on in silicio modeling.
logically should result
That’s theory-based reasoning and not empirical evidence based. Sarah Constantin says that everything is theory-based reasoning (supported by computer modeling) and Dentin argues that they not only do theory-based reasoning but also have empiric evidence for individual peptides.
While it does seem there was a certain amount of shotgun aproach following a few different lines of reasoning, that critism is difficult to square with actually reading the paper. It looks like the peptide selection was largely empirical and cited. The decisions about how to actually package that info into a vacine is largely educated guesswork (as you say theory, supported by computer modeling).
“Mapping of linear B-cell epitopes by binding antibodies in convalescent sera to a library of peptides representing viral antigens. A strong signal in a linear epitope mapping study does not guarantee that the epitope peptide in the context of a vaccine will trigger the production of an antibody that binds to this epitope within the context of the virus. However, it is a good indicator that this is at least possible.”
Or as I understood from elsewhere: present antibodies from recovered people to every possible short peptide sequence and see which ones they actually attacked. Make the inference that people with less severe infection had better antibodies than those with more severe symptoms in the event antibodies differed. Package a selection of promising looking pepties into a vacine; choose enough that there’s likely multiple effective peptides even if 2/3rds of the choices are duds.
Doesn’t this speak to your concern:
They perform the substitution to keep the shape that our immune system is looking for by recreating a disulfide bond that to form a loop with the same sequence the B-cells are targeting in the virus.
While I agree their expression was “potentially beneficial” (or close) it seems clear to me the point was our B-cells are bonding to that loop and if there are not other aspect in the larger peptide that lead the cell to that site for bonding, construction the loop via the disulfide bond they introduce logically should result in triggering an immune response.
I’m not sure why they would need to provide some type of citation for this, much less that they would even have a source for this specific application.
The argument about the substition of the amino acids looks to me like it rests completely on in silicio modeling.
That’s theory-based reasoning and not empirical evidence based. Sarah Constantin says that everything is theory-based reasoning (supported by computer modeling) and Dentin argues that they not only do theory-based reasoning but also have empiric evidence for individual peptides.
While it does seem there was a certain amount of shotgun aproach following a few different lines of reasoning, that critism is difficult to square with actually reading the paper. It looks like the peptide selection was largely empirical and cited. The decisions about how to actually package that info into a vacine is largely educated guesswork (as you say theory, supported by computer modeling).
“Mapping of linear B-cell epitopes by binding antibodies in convalescent
sera to a library of peptides representing viral antigens. A strong signal in a
linear epitope mapping study does not guarantee that the epitope peptide
in the context of a vaccine will trigger the production of an antibody that
binds to this epitope within the context of the virus. However, it is a good
indicator that this is at least possible.”
Or as I understood from elsewhere: present antibodies from recovered people to every possible short peptide sequence and see which ones they actually attacked. Make the inference that people with less severe infection had better antibodies than those with more severe symptoms in the event antibodies differed. Package a selection of promising looking pepties into a vacine; choose enough that there’s likely multiple effective peptides even if 2/3rds of the choices are duds.