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If there is an expert in immunology here I'd really like to ask a question: Aren't antibody titers just one measure of immunity? Since ~everyone with just two

If there is an expert in immunology here I'd really like to ask a question: Aren't antibody titers just one measure of immunity? Since ~everyone with just two shots get them a while ago, and people receiving the boosters are receiving them now, wouldn't we expect must higher levels of neutralizing antibodies in boosted people? I know the number of antibodies fades over time, (whether from vaccine or infection) but this doesn't mean you don't have lasting protection after this, right? Wouldn't it therefore be a mistake/misleading to conclude something specific about a level of protection from this titer data alone?

lambdaba 5y ago
Not the expert you were asking but one thing I know is natural immunity isn't just antibodies, which is why traditional inactivated vaccines yield more robust and long-lasting protection.
- javagram 5y ago
  FYI, vector vaccines and mRNA vaccines also create t-cell immunity , not just antibodies. It’s not just “inactivated vaccines” that do so.
  - lambdaba 5y ago
    I did not know that. Thank you. Possibly in lesser quantities though? It is only related to the spike protein in the case of Covid. As I understand the natural immunity has a different fingerprint even with covid?
    - javagram 5y ago
      "natural" immunity would create antibodies and immunity that may be related to non-spike proteins of COVID-19 (I believe this depends on your own body's response and the severity of infection exactly what is generated). The vector and mRNA vaccines only expose the spike protein (in various forms), so they don't generate immunity to other proteins of COVID-19.
- q1w2 5y ago
  > traditional inactivated vaccines yield more robust and long-lasting protection This is wrong. The formation of memory T/B cells has nothing to do with the vaccine tech. Both create lasting T/B cell memory immunity. The problem is that it takes a week or so for T/B immunity to kick in - so you still get sick.
  - lambdaba 5y ago
    Thank you. Shouldn't have said that with such certainty. But maybe perhaps having just the spike protein vs the whole virus is eliciting a different response? Again, I don't know.
codeulike 5y ago
There's the whole t-cell and b-cell stuff that protects from serious disease but it's much harder to test/measure so you don't get these rapid headline grabbing lab studies. T-cells as I understand it are much less likely to be thrown off by spike mutations because they react to whole genome of virus (edit: T-cells from an infection that is).
- lordlimecat 5y ago
  This is not my area but isn't the point of the mRNA vaccines that that virus' DNA is never introduced into your body? You only end up with a narrow transcribed slice of that DNA targeting a specific protein. I've also never heard of your immune system targetting a genome; how is it generally gaining access to that genome when it is encapsulated? My understanding of the spike targeting is that COVID is only so infectious because of the specific configuration of that spike protein. Change it too much, and it stops being nearly as infectious (and thus stops being COVID as we know it).
  - codeulike 5y ago
    oh yeah thats a point, t-cells will only be able to react to the things that they've seen
- jjtheblunt 5y ago
  > because they react to whole genome of virus Why do you think that? A genome codes for protein production. T-cells are something like a Unix grep for protein sequences (instead of character regexes) with their grep argument a memorized protein sequence to recognize in the wild. So it's some sort of dumb luck if the entirety of proteins, specified in a genome's blueprints, would happen to have t-cells assigned to recognize all of them.
  - codeulike 5y ago
    Good question. My vague understanding is that antibodies react to the external shape of the virus, the spike and so on. Whereas T-cells react to the little chunks of rna produced during multiplication of the virus, kindof the byprodyucts of a virus-factory-cell, and as such are not restricted to the 'outside' of the virus but can potentially learn about any part of the virus' genome. Hence T-cells are less likely to be thrown off by spike mutations. But my grasp on this is very vague.
l33tman 5y ago
From what I can remember from my immunology class, B-cells specific to a particular antibody will detect the antigen in a re-infection, start to massively clone themselves and quickly increase the specific antibody titer in the blood in response. It doesn't make sense from an energy point of view for these to get produced in large volumes in the blood forever, so unless you're continually re-infected, the antibody titers will then drop but the memory B-cells remain, ready for a new round. What's crucial is how fast the immune system can ramp up again in a re-infection, perhaps for COVID19 this is almost always fast enough to prevent a deadly re-infection but not fast enough to prevent any form of viral replication and shedding and this is why vaccinated still spread the virus around (and this might keep being the case with the current type of vaccines for corona viruses unless you deal out 10 billion booster doses every quarter). So the question is complex and depends on what your goals are, and all of this has to be dumbed down in a way for consumption by the general public who just want to know "how long is my vaccine good for"... :/ Perhaps the antibody blood titer is not the only data that is relevant, but maybe it's determined that it correlates to one of the outcomes in a good enough way..
shmatt 5y ago
Hospitalization and death numbers are definitely directly connected to how long its been since you got your shot. So for now, it does not seem like the whole long immunity/T-B-cell thing is happening with Pfizer/Moderna/J&J at least There is a very real per month affect, every month after your latest mRNA shot, your chances of getting seriously sick get a little bigger. After 6 months they get so big that scientists concluded its time for a booster. Now we wait and see, but so far things seem to be trending in the same direction, in Israel at least (so, no Moderna or J&J). Its not that we are only measuring titers. Its that vaccinated people are suddenly dying. So there seems to be no or very low memory to making more titers Then, people get a booster, and boom, 90% lower chance of death again with high titers https://www.nejm.org/doi/full/10.1056/NEJMoa2114228 https://www.nejm.org/doi/full/10.1056/NEJMoa2114228 https://www.science.org/doi/10.1126/science.abm0620 https://www.science.org/doi/10.1126/science.abm0620 The veteran research which had 800,000 participants showed terrible long term results for J&J
- nullc 5y ago
  > Hospitalization and death numbers are definitely directly connected There has never been a RCT which showed covid vaccination reduces mortality. I believe they do but this has not been rigorously shown. Unfortunately, even though we've had gigantic RCTs on covid none of them showed statistically significant covid-mortality in the unvaccinated population (potentially due to prescreening eliminating people who were at risk of dying), so they weren't able to show any improvement. Numbers from the population have been suggestive, but unfortunately you can get the same graphs -- an initial spike of reduced mortality with a pronounced fall off in effectiveness -- from a simulation where the vaccine has no effect on mortality at all. The reason for this is that our stats on the public measure time lagged mortality against current vaccination numbers. People reported dead today actually died a week before and got sick two weeks before that. When the increase in new vaccination is high, you will overestimate the size of the population for the people who died and falsely think the vaccine is more effective than it is. And you end up with your 'per month effect' -- the same statistical error will make the cycle nicely repeat with boosters due to the same population size error for the newly boosted population. This is the sort of bias that is structurally eliminated in RCT design and hard to avoid in population monitoring.
dragontamer 5y ago
> Aren't antibody titers just one measure of immunity? Yes. But Omicron just came out 3 weeks ago. -------- We start with the quickest measures of immunity. As better data comes in, we change our opinion. The gold-standard is a large-scale, multi-month A/B test. There simply hasn't been enough time for that to be created. If these smaller tests prove adequate, we probably will skip the large-scale test... much like Alpha and Delta, it seems like these variants don't last very long in practice. We just barely finished studying Delta's effects across a variety of treatments, and all of that data is about to become obsolete with a new variant.
- dolni 5y ago
  > We start with the quickest measures of immunity. As better data comes in, we change our opinion. This is exactly the problem with pandemic messaging. Too many claims based on garbage data that end up being wrong later. The result is a population that doesn't trust its government's guidance. Vaccines were supposed to end the pandemic. Then it was they would keep you from getting sick. Then it was you'd still get sick, but you wouldn't spread it. Now it's you'll still get sick and you'll still spread it, but you won't die.
  - dragontamer 5y ago
    > This is exactly the problem with pandemic messaging There's two parts to the pandemic. Gathering information, and spreading information. You need to spread the currently known things, so that scientists know what else to look for. Welcome to the world of science and learning. You know one thing, and then it changes as new tests come in. Its impossible to get to the truth from the beginning in one step.
    - dolni 5y ago
      On the contrary -- welcome to the world trust building. If you only know one thing, you keep your mouth shut until you know more. And if the thing you know isn't actually known, like how effective the vaccine really is, that goes double. Notice that doesn't require you to "know the truth from the beginning in one step." It requires the people in charge to show some restraint. You only get so many opportunities to be wrong before that trust is eroded.
packetlost 5y ago
Not an immunology expert, but the focus on antibody titers seems to reek of corporate conflict of interest. It's pretty well understood that antibodies will break down and mostly fall to undetectable levels after a few months of an infection (in most cases, and in individuals who actually produce antibodies, not everyone will such as immune-compromised people) , but there's a huge financial incentive for vaccine producers to focus on these studies because it paints the picture that people need continuous boosters for protection. That being said, it's harder to detect other forms of immunity such as memory T and B cells, so it's not like the studies are completely disingenuous, it's just easier to do the studies that way. At this point in the pandemic, I think full immunity shouldn't be the goal for most individuals. COVID and it's variants are never going away, so unless you are high risk, live with someone who is high risk, or travel a lot, the first round of vaccinations should be good enough to prevent serious illness in most individuals for a long time, at least until a variant that changes the spike protein enough comes around. At which point, to my understanding, the efficacy of most vaccines will drop significantly below natural infection, as most target specific protein structures on the virus capsid (in this case, the "spike protein").
- q1w2 5y ago
  Your first sentence is contradicted by the last sentence in your first paragraph (which is correct). B-Cell immunity is much much harder to detect and cannot be done in any test given to the public. It's also difficult to determine from a positive b-cell result whether that person will have a strong or weak immune response - and how soon. I think everyone in the immunology community is aware of the limitations of antibody tests, but I think it's wrong to attribute how it's portrayed in the media as corporate conflict of interest. My impression is that it the media needs simple stories to build their narratives and cannot complicate things with b-cell immunity. I agree with everything else you said, but I think the story for yearly (maybe bi-yearly) covid vaccines, as we have with flu, have a very strong case even given immunity memory cells.
  - packetlost 5y ago
    The sentences don't really contradict, both can be true (though I will concede the first sentence is not immediately relevant to this particular study). My whole point is that the focus on immunity (vs mild cases) by vaccine manufacturers is potentially misguided and incentivized by selling more boosters.

lambdaba 5y ago

Not the expert you were asking but one thing I know is natural immunity isn't just antibodies, which is why traditional inactivated vaccines yield more robust and long-lasting protection.

javagram 5y ago
FYI, vector vaccines and mRNA vaccines also create t-cell immunity , not just antibodies. It’s not just “inactivated vaccines” that do so.
- lambdaba 5y ago
  I did not know that. Thank you. Possibly in lesser quantities though? It is only related to the spike protein in the case of Covid. As I understand the natural immunity has a different fingerprint even with covid?
  - javagram 5y ago
    "natural" immunity would create antibodies and immunity that may be related to non-spike proteins of COVID-19 (I believe this depends on your own body's response and the severity of infection exactly what is generated). The vector and mRNA vaccines only expose the spike protein (in various forms), so they don't generate immunity to other proteins of COVID-19.
q1w2 5y ago
> traditional inactivated vaccines yield more robust and long-lasting protection This is wrong. The formation of memory T/B cells has nothing to do with the vaccine tech. Both create lasting T/B cell memory immunity. The problem is that it takes a week or so for T/B immunity to kick in - so you still get sick.
- lambdaba 5y ago
  Thank you. Shouldn't have said that with such certainty. But maybe perhaps having just the spike protein vs the whole virus is eliciting a different response? Again, I don't know.

codeulike 5y ago

There's the whole t-cell and b-cell stuff that protects from serious disease but it's much harder to test/measure so you don't get these rapid headline grabbing lab studies. T-cells as I understand it are much less likely to be thrown off by spike mutations because they react to whole genome of virus (edit: T-cells from an infection that is).

lordlimecat 5y ago
This is not my area but isn't the point of the mRNA vaccines that that virus' DNA is never introduced into your body? You only end up with a narrow transcribed slice of that DNA targeting a specific protein. I've also never heard of your immune system targetting a genome; how is it generally gaining access to that genome when it is encapsulated? My understanding of the spike targeting is that COVID is only so infectious because of the specific configuration of that spike protein. Change it too much, and it stops being nearly as infectious (and thus stops being COVID as we know it).
- codeulike 5y ago
  oh yeah thats a point, t-cells will only be able to react to the things that they've seen
jjtheblunt 5y ago
> because they react to whole genome of virus Why do you think that? A genome codes for protein production. T-cells are something like a Unix grep for protein sequences (instead of character regexes) with their grep argument a memorized protein sequence to recognize in the wild. So it's some sort of dumb luck if the entirety of proteins, specified in a genome's blueprints, would happen to have t-cells assigned to recognize all of them.
- codeulike 5y ago
  Good question. My vague understanding is that antibodies react to the external shape of the virus, the spike and so on. Whereas T-cells react to the little chunks of rna produced during multiplication of the virus, kindof the byprodyucts of a virus-factory-cell, and as such are not restricted to the 'outside' of the virus but can potentially learn about any part of the virus' genome. Hence T-cells are less likely to be thrown off by spike mutations. But my grasp on this is very vague.

l33tman 5y ago

From what I can remember from my immunology class, B-cells specific to a particular antibody will detect the antigen in a re-infection, start to massively clone themselves and quickly increase the specific antibody titer in the blood in response. It doesn't make sense from an energy point of view for these to get produced in large volumes in the blood forever, so unless you're continually re-infected, the antibody titers will then drop but the memory B-cells remain, ready for a new round. What's crucial is how fast the immune system can ramp up again in a re-infection, perhaps for COVID19 this is almost always fast enough to prevent a deadly re-infection but not fast enough to prevent any form of viral replication and shedding and this is why vaccinated still spread the virus around (and this might keep being the case with the current type of vaccines for corona viruses unless you deal out 10 billion booster doses every quarter). So the question is complex and depends on what your goals are, and all of this has to be dumbed down in a way for consumption by the general public who just want to know "how long is my vaccine good for"... :/ Perhaps the antibody blood titer is not the only data that is relevant, but maybe it's determined that it correlates to one of the outcomes in a good enough way..

shmatt 5y ago

Hospitalization and death numbers are definitely directly connected to how long its been since you got your shot. So for now, it does not seem like the whole long immunity/T-B-cell thing is happening with Pfizer/Moderna/J&J at least There is a very real per month affect, every month after your latest mRNA shot, your chances of getting seriously sick get a little bigger. After 6 months they get so big that scientists concluded its time for a booster. Now we wait and see, but so far things seem to be trending in the same direction, in Israel at least (so, no Moderna or J&J). Its not that we are only measuring titers. Its that vaccinated people are suddenly dying. So there seems to be no or very low memory to making more titers Then, people get a booster, and boom, 90% lower chance of death again with high titers https://www.nejm.org/doi/full/10.1056/NEJMoa2114228 https://www.nejm.org/doi/full/10.1056/NEJMoa2114228 https://www.science.org/doi/10.1126/science.abm0620 https://www.science.org/doi/10.1126/science.abm0620 The veteran research which had 800,000 participants showed terrible long term results for J&J

nullc 5y ago
> Hospitalization and death numbers are definitely directly connected There has never been a RCT which showed covid vaccination reduces mortality. I believe they do but this has not been rigorously shown. Unfortunately, even though we've had gigantic RCTs on covid none of them showed statistically significant covid-mortality in the unvaccinated population (potentially due to prescreening eliminating people who were at risk of dying), so they weren't able to show any improvement. Numbers from the population have been suggestive, but unfortunately you can get the same graphs -- an initial spike of reduced mortality with a pronounced fall off in effectiveness -- from a simulation where the vaccine has no effect on mortality at all. The reason for this is that our stats on the public measure time lagged mortality against current vaccination numbers. People reported dead today actually died a week before and got sick two weeks before that. When the increase in new vaccination is high, you will overestimate the size of the population for the people who died and falsely think the vaccine is more effective than it is. And you end up with your 'per month effect' -- the same statistical error will make the cycle nicely repeat with boosters due to the same population size error for the newly boosted population. This is the sort of bias that is structurally eliminated in RCT design and hard to avoid in population monitoring.

dragontamer 5y ago

> Aren't antibody titers just one measure of immunity? Yes. But Omicron just came out 3 weeks ago. -------- We start with the quickest measures of immunity. As better data comes in, we change our opinion. The gold-standard is a large-scale, multi-month A/B test. There simply hasn't been enough time for that to be created. If these smaller tests prove adequate, we probably will skip the large-scale test... much like Alpha and Delta, it seems like these variants don't last very long in practice. We just barely finished studying Delta's effects across a variety of treatments, and all of that data is about to become obsolete with a new variant.

dolni 5y ago
> We start with the quickest measures of immunity. As better data comes in, we change our opinion. This is exactly the problem with pandemic messaging. Too many claims based on garbage data that end up being wrong later. The result is a population that doesn't trust its government's guidance. Vaccines were supposed to end the pandemic. Then it was they would keep you from getting sick. Then it was you'd still get sick, but you wouldn't spread it. Now it's you'll still get sick and you'll still spread it, but you won't die.
- dragontamer 5y ago
  > This is exactly the problem with pandemic messaging There's two parts to the pandemic. Gathering information, and spreading information. You need to spread the currently known things, so that scientists know what else to look for. Welcome to the world of science and learning. You know one thing, and then it changes as new tests come in. Its impossible to get to the truth from the beginning in one step.
  - dolni 5y ago
    On the contrary -- welcome to the world trust building. If you only know one thing, you keep your mouth shut until you know more. And if the thing you know isn't actually known, like how effective the vaccine really is, that goes double. Notice that doesn't require you to "know the truth from the beginning in one step." It requires the people in charge to show some restraint. You only get so many opportunities to be wrong before that trust is eroded.

packetlost 5y ago

Not an immunology expert, but the focus on antibody titers seems to reek of corporate conflict of interest. It's pretty well understood that antibodies will break down and mostly fall to undetectable levels after a few months of an infection (in most cases, and in individuals who actually produce antibodies, not everyone will such as immune-compromised people) , but there's a huge financial incentive for vaccine producers to focus on these studies because it paints the picture that people need continuous boosters for protection. That being said, it's harder to detect other forms of immunity such as memory T and B cells, so it's not like the studies are completely disingenuous, it's just easier to do the studies that way. At this point in the pandemic, I think full immunity shouldn't be the goal for most individuals. COVID and it's variants are never going away, so unless you are high risk, live with someone who is high risk, or travel a lot, the first round of vaccinations should be good enough to prevent serious illness in most individuals for a long time, at least until a variant that changes the spike protein enough comes around. At which point, to my understanding, the efficacy of most vaccines will drop significantly below natural infection, as most target specific protein structures on the virus capsid (in this case, the "spike protein").

q1w2 5y ago
Your first sentence is contradicted by the last sentence in your first paragraph (which is correct). B-Cell immunity is much much harder to detect and cannot be done in any test given to the public. It's also difficult to determine from a positive b-cell result whether that person will have a strong or weak immune response - and how soon. I think everyone in the immunology community is aware of the limitations of antibody tests, but I think it's wrong to attribute how it's portrayed in the media as corporate conflict of interest. My impression is that it the media needs simple stories to build their narratives and cannot complicate things with b-cell immunity. I agree with everything else you said, but I think the story for yearly (maybe bi-yearly) covid vaccines, as we have with flu, have a very strong case even given immunity memory cells.
- packetlost 5y ago
  The sentences don't really contradict, both can be true (though I will concede the first sentence is not immediately relevant to this particular study). My whole point is that the focus on immunity (vs mild cases) by vaccine manufacturers is potentially misguided and incentivized by selling more boosters.