Thanks for your great articles on this. As you say, it's good to have corroborating studies, but not good news. I was recently at retreat with a large vaccinated population and was surprised about how many got significantly ill and tested positive on a PCR test in the middle of summer. I don't know the status of their previous covid illnesses except for two of them, this was their second and third bout of covid-like illnes. I know two other people who keep getting ill with colds every couple months.
I mentioned this in I believe the Irgang, et al. (or was it Irrang?), or at least one of those IgG4 papers, that if you look at the supplemental material there was an apparent discrepancy where one person seemed to be a super IgG4 converter (around 30ish%?) while most people were around 10ish. It seemed that the 22% (can't recall the actual number) was biased high by a select few super responders.
It'd be interesting why some people show this high conversion rate, but that seems to be the next question to be answered.
Right, but when looking at antibodies you can see that there is individual variation but it is not clear how much of this variation is just driven by overall higher response, which dot is which on the IgG4 graph and the IgG1 graph, if this high IgG4 dot is even higher in IgG1 (relative to everyone else) then they are actually lower in terms of conversion of the overall anti-spike B Cell pool. Like how California has more Red voters than most Red states in absolute terms - you need to know the proportion in each state.
The only thing really is that I remembered after posting that this was already in Irrgang et al, just not as clearly shown in before and after format.
"The new preprint measures this. Overall IgG4 is not increased very much. (Therefore concerns generically related to diseases involving high overall IgG4 are probably not warranted, pending future changes.)"
But what about Fc-Fc binding, and the associated ability of these IgG4 antibodies to neuter the ability of good antibodies to take the fight to...let's say... a small incipient cancer? My contention is that a little IgG4 can go a long way. Why? Because IgG4 doesn't do it's Fc-Fc damage to the sea of antibodies floating around in the general population....no, it does this non-specifically to those good IgG antibodies that have found, and bound to, their target.
"IgG4 binds to solid-phase bound IgG1, but solid-phase bound IgG4 does not bind IgG1
Previously, IgG4 Fc binding was observed in assays with Fc or intact IgG coupled to a solid support (6) or to IgG subclasses in an immunoblot (9). In Fig. 2,A, we compared binding of 125I-labeled IgG1 or IgG4 to Sepharose-coupled IgG1 or IgG4. IgG4 binds both to coupled IgG1 and IgG4. Binding to IgG1 appears to be slightly more efficient, but IgG4 Fc binding during the coupling of IgG4 could reduce the capacity of the IgG4-Sepharose. Surprisingly, IgG1 does not bind to Sepharose-coupled IgG4, which implies the binding activity of IgG4 to be restricted to IgG coupled to a solid support. This suggests that IgG4 Fc-binding activity is directed either against epitopes that become available only after coupling...."
Right, but even if a little goes a long way there is already a little, all the time. So we want to ask the question, does this actually change the overall amount very much? With measuring antibodies that is a difficult question because you have a lot of individual variation on log scales all the time, typically you need really big differences to know there is really a difference. So using B Cell isotope proportion is nice, and here there doesn't seem to be any movement.
This is fascinating that they think the length of days in between is the most likely reason instead of the mRNA brand new technology... cant taint that mRNA technology when there are so many possible lucrative products they can still shove it into and plow into the masses..
I don't think the comment was intended to infer that mRNA's are safer. One thing we have to consider is the factual basis of the argument, in that it appears that timing has been a factor that has been grossly overlooked. So maybe it's related to the mRNA, maybe it's the timing, or maybe both. One doesn't really exclude the other.
Thanks for your great articles on this. As you say, it's good to have corroborating studies, but not good news. I was recently at retreat with a large vaccinated population and was surprised about how many got significantly ill and tested positive on a PCR test in the middle of summer. I don't know the status of their previous covid illnesses except for two of them, this was their second and third bout of covid-like illnes. I know two other people who keep getting ill with colds every couple months.
So it's possibly a good thing that my first series of Moderna shots were a little over a month apart…
By then I had smartened up and got no boosters.
Possibly. Can't actually be researched, like I say, unfortunately. Against the rules.
I'll grasp at whatever straws are offered ;)
I mentioned this in I believe the Irgang, et al. (or was it Irrang?), or at least one of those IgG4 papers, that if you look at the supplemental material there was an apparent discrepancy where one person seemed to be a super IgG4 converter (around 30ish%?) while most people were around 10ish. It seemed that the 22% (can't recall the actual number) was biased high by a select few super responders.
It'd be interesting why some people show this high conversion rate, but that seems to be the next question to be answered.
Right, but when looking at antibodies you can see that there is individual variation but it is not clear how much of this variation is just driven by overall higher response, which dot is which on the IgG4 graph and the IgG1 graph, if this high IgG4 dot is even higher in IgG1 (relative to everyone else) then they are actually lower in terms of conversion of the overall anti-spike B Cell pool. Like how California has more Red voters than most Red states in absolute terms - you need to know the proportion in each state.
The only thing really is that I remembered after posting that this was already in Irrgang et al, just not as clearly shown in before and after format.
"The new preprint measures this. Overall IgG4 is not increased very much. (Therefore concerns generically related to diseases involving high overall IgG4 are probably not warranted, pending future changes.)"
But what about Fc-Fc binding, and the associated ability of these IgG4 antibodies to neuter the ability of good antibodies to take the fight to...let's say... a small incipient cancer? My contention is that a little IgG4 can go a long way. Why? Because IgG4 doesn't do it's Fc-Fc damage to the sea of antibodies floating around in the general population....no, it does this non-specifically to those good IgG antibodies that have found, and bound to, their target.
https://journals.aai.org/jimmunol/article/182/7/4275/81101/Human-IgG4-Binds-to-IgG4-and-Conformationally
"IgG4 binds to solid-phase bound IgG1, but solid-phase bound IgG4 does not bind IgG1
Previously, IgG4 Fc binding was observed in assays with Fc or intact IgG coupled to a solid support (6) or to IgG subclasses in an immunoblot (9). In Fig. 2,A, we compared binding of 125I-labeled IgG1 or IgG4 to Sepharose-coupled IgG1 or IgG4. IgG4 binds both to coupled IgG1 and IgG4. Binding to IgG1 appears to be slightly more efficient, but IgG4 Fc binding during the coupling of IgG4 could reduce the capacity of the IgG4-Sepharose. Surprisingly, IgG1 does not bind to Sepharose-coupled IgG4, which implies the binding activity of IgG4 to be restricted to IgG coupled to a solid support. This suggests that IgG4 Fc-binding activity is directed either against epitopes that become available only after coupling...."
Right, but even if a little goes a long way there is already a little, all the time. So we want to ask the question, does this actually change the overall amount very much? With measuring antibodies that is a difficult question because you have a lot of individual variation on log scales all the time, typically you need really big differences to know there is really a difference. So using B Cell isotope proportion is nice, and here there doesn't seem to be any movement.
This is fascinating that they think the length of days in between is the most likely reason instead of the mRNA brand new technology... cant taint that mRNA technology when there are so many possible lucrative products they can still shove it into and plow into the masses..
I don't think the comment was intended to infer that mRNA's are safer. One thing we have to consider is the factual basis of the argument, in that it appears that timing has been a factor that has been grossly overlooked. So maybe it's related to the mRNA, maybe it's the timing, or maybe both. One doesn't really exclude the other.