Interesting debate going here on OAS. You make some good points, it seems. Doesn't the real world data, such as we have, make it pretty certain that the vaxxed are indeed getting Omicron at higher rates? If not OAS, what is it?
I really would love if we could get granular, high quality data on who exactly is getting infected and when acr…
Interesting debate going here on OAS. You make some good points, it seems. Doesn't the real world data, such as we have, make it pretty certain that the vaxxed are indeed getting Omicron at higher rates? If not OAS, what is it?
I really would love if we could get granular, high quality data on who exactly is getting infected and when across all categories. Unvaxxed naive, vaxxed naive, unvaxxed natural immunity, vaxxed natural immunity, boosted naive and NI, how long since last dose, when were previous infections, etc.
Raw "negative efficacy" would not support OAS. OAS implies that something is "bad" (i.e. sinful) in real life about the inability to trick the immune system into making antibodies against A' after tricking it to make antibodies against A. Mere higher susceptibility to A' wouldn't be OAS: since you can't make antibodies to A' before infection, saying "reduced ability to make antibodies to A' causes the infection that has to precede making antibodies to A'" is logically incoherent.
So what would negative efficacy imply? Antibodies against A enhance infection by A' - which is more like Antibody Dependent Enhancement. Vanden Bossche has offered a very plausible mechanism, which I recycled for a post in https://unglossed.substack.com/p/neg
Now that almost everybody has been either exposed to many different variants or vaccinated, everybody has some imprinting (either natural or via vaccine).
Two questions:
1. If we were able to predict next variant A' (which we obviously can't) and vaccinate against that variant before it hit (now we can produce antibodies A' *before* we get infected) , wouldn't OAS mean that previously vaccinated would be more susceptible?
2. But the same thing also applies for people that were naturally infected.
Imprinting happens there as well. Right? This is what happens with flu. Immune system is imprinted with the first flu you encounter.
Let’s assume natural immunity against A is superior to artificial immunity against A’ because mucosal /cellular immune programming + related antigen recognition.
Are people juiced up with A’ antibodies better off than people juiced up with A antibodies (who now can’t have their artificial programming rewritten) in challenge with A’? Well, actually, maybe not - maybe a bit of difference leads to an enriched or more robust “immune correction” while still protecting against viremia. The funny thing is that OAS isn’t even sure which answer confirms the “sin” - a Eugyppius can fire off a post saying either result is proof of OAS!
Yes, and the more I look into both OAS and ADE the murkier it is.
And let's face it, because the data is so crappy (either by design or by incompetence) it's hard enough to see through the fog
if you are genuinely trying to uncover the truth. If you are just searching for confirmation of your prior belief or your hypothesis, then it's great because you can show pretty much anything.
It's also interesting that OAS might have occurred with H1N1
And these mRNA (and adenovirus) vaccines were developed and sold with the premise that we know exactly what happens in our body and what those developed antibodies will do.
Hmmm, I thought - in layman's terms - OAS (immune imprinting) basically meant that your first immune response to a pathogen set the tone for future immune responses to the same or similar pathogen. A suboptimal original immune response, in the case of the mRNA vaccine because it was specific to the S protein instead of the whole virus. This might result in a decreased ability to stave off subsequent symptomatic infections but shouldn't compromise the immune system's ability to combat severe illness so much. ADE, on the other hand, results in your immune system's inability to generate antibodies that are capable of recognizing and attacking the mutated virus. This essentially clears the way for the mutated variant to replicate unchecked, which results in a much greater vulnerability to both infection and severe illness.
The data we're seeing, mostly from other countries thus far, on Omicron seems to be suggesting an affinity for infecting vaccinated / boosted individuals relative to the unvaccinated, but not necessarily leading to more severe illness than in the vaccinated. So why wouldn't that be a greater signal of OAS than ADE? I mean, assuming OAS was actually a thing (I know you don't).
Because negative efficacy ≠ OAS. OAS is totally narrowly focused on generation of novel antibodies and has nothing to say about anything we know about immunity after 1960 - but it still retains "relevance" for vaccination. Lower-than-naive antigenic sensitivity to homologous versions of an antigen mean vaccination cannot generate antibodies to the homologous version. But *does* lower-than-naive antigenic sensitivity to homologous versions of previously-sensitized antigens have a real world relevance, even for the vaccinated? Neither "antibodies can mess up infection in other ways" nor "vaccine-induced immune response fails to induce the full suite of cellular memory immunity that we've come to discover after OAS was theorized" satisfy OAS. It's like asking whether nuclear fission "is alchemy."
Just one point I wanted to make.... I don't think my simplification was implying that negative efficacy = OAS. Rather, it's breaking efficacy down into the individual components of infection, illness and death and then assigning them to possible differentiating signals . Or maybe what you're saying is that no matter which of those components you select, it doesn't or can't be a signal of OAS. It's probably that. Thanks for the response.
Interesting debate going here on OAS. You make some good points, it seems. Doesn't the real world data, such as we have, make it pretty certain that the vaxxed are indeed getting Omicron at higher rates? If not OAS, what is it?
I really would love if we could get granular, high quality data on who exactly is getting infected and when across all categories. Unvaxxed naive, vaxxed naive, unvaxxed natural immunity, vaxxed natural immunity, boosted naive and NI, how long since last dose, when were previous infections, etc.
Raw "negative efficacy" would not support OAS. OAS implies that something is "bad" (i.e. sinful) in real life about the inability to trick the immune system into making antibodies against A' after tricking it to make antibodies against A. Mere higher susceptibility to A' wouldn't be OAS: since you can't make antibodies to A' before infection, saying "reduced ability to make antibodies to A' causes the infection that has to precede making antibodies to A'" is logically incoherent.
So what would negative efficacy imply? Antibodies against A enhance infection by A' - which is more like Antibody Dependent Enhancement. Vanden Bossche has offered a very plausible mechanism, which I recycled for a post in https://unglossed.substack.com/p/neg
Now that almost everybody has been either exposed to many different variants or vaccinated, everybody has some imprinting (either natural or via vaccine).
Two questions:
1. If we were able to predict next variant A' (which we obviously can't) and vaccinate against that variant before it hit (now we can produce antibodies A' *before* we get infected) , wouldn't OAS mean that previously vaccinated would be more susceptible?
2. But the same thing also applies for people that were naturally infected.
Imprinting happens there as well. Right? This is what happens with flu. Immune system is imprinted with the first flu you encounter.
Let’s assume natural immunity against A is superior to artificial immunity against A’ because mucosal /cellular immune programming + related antigen recognition.
Are people juiced up with A’ antibodies better off than people juiced up with A antibodies (who now can’t have their artificial programming rewritten) in challenge with A’? Well, actually, maybe not - maybe a bit of difference leads to an enriched or more robust “immune correction” while still protecting against viremia. The funny thing is that OAS isn’t even sure which answer confirms the “sin” - a Eugyppius can fire off a post saying either result is proof of OAS!
Yes, and the more I look into both OAS and ADE the murkier it is.
And let's face it, because the data is so crappy (either by design or by incompetence) it's hard enough to see through the fog
if you are genuinely trying to uncover the truth. If you are just searching for confirmation of your prior belief or your hypothesis, then it's great because you can show pretty much anything.
It's also interesting that OAS might have occurred with H1N1
https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC3165229/
but it's remarkable that we really don't know much and for sure.
It's also clear that many vaccines are a product of guess as opposed to deep and solid understanding:
https://www.nature.com/articles/nm1216
And these mRNA (and adenovirus) vaccines were developed and sold with the premise that we know exactly what happens in our body and what those developed antibodies will do.
Hmmm, I thought - in layman's terms - OAS (immune imprinting) basically meant that your first immune response to a pathogen set the tone for future immune responses to the same or similar pathogen. A suboptimal original immune response, in the case of the mRNA vaccine because it was specific to the S protein instead of the whole virus. This might result in a decreased ability to stave off subsequent symptomatic infections but shouldn't compromise the immune system's ability to combat severe illness so much. ADE, on the other hand, results in your immune system's inability to generate antibodies that are capable of recognizing and attacking the mutated virus. This essentially clears the way for the mutated variant to replicate unchecked, which results in a much greater vulnerability to both infection and severe illness.
The data we're seeing, mostly from other countries thus far, on Omicron seems to be suggesting an affinity for infecting vaccinated / boosted individuals relative to the unvaccinated, but not necessarily leading to more severe illness than in the vaccinated. So why wouldn't that be a greater signal of OAS than ADE? I mean, assuming OAS was actually a thing (I know you don't).
Because negative efficacy ≠ OAS. OAS is totally narrowly focused on generation of novel antibodies and has nothing to say about anything we know about immunity after 1960 - but it still retains "relevance" for vaccination. Lower-than-naive antigenic sensitivity to homologous versions of an antigen mean vaccination cannot generate antibodies to the homologous version. But *does* lower-than-naive antigenic sensitivity to homologous versions of previously-sensitized antigens have a real world relevance, even for the vaccinated? Neither "antibodies can mess up infection in other ways" nor "vaccine-induced immune response fails to induce the full suite of cellular memory immunity that we've come to discover after OAS was theorized" satisfy OAS. It's like asking whether nuclear fission "is alchemy."
I said layman's terms! LOL.
Just one point I wanted to make.... I don't think my simplification was implying that negative efficacy = OAS. Rather, it's breaking efficacy down into the individual components of infection, illness and death and then assigning them to possible differentiating signals . Or maybe what you're saying is that no matter which of those components you select, it doesn't or can't be a signal of OAS. It's probably that. Thanks for the response.