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ELI5 : what does it mean in practice for vaccine and booster schedules ? Are we heading towards "no less than one booster every year" ? Or the contrary ? Would

ELI5 : what does it mean in practice for vaccine and booster schedules ? Are we heading towards "no less than one booster every year" ? Or the contrary ? Would it change the frequency / severity of side effects with successive boosters ? Basically, is it "good" news, "bad" news, or just, news ? (To clarify in case that's what caused the downvotes : I'm not writing "bad" news because I think vaccines are "bad". If we really need to get boosted once a year, so be it - but it would arguably be a worse outcome than "not needing it")

ergonaught 4y ago
It isn't news. It's science. "Further investigations are needed to clarify the precise immunological mechanisms driving this response and to evaluate whether an IgG4-driven antibody response affects subsequent viral infections and booster vaccinations. This is not only relevant for potential future vaccine campaigns against SARS-CoV-2, but also for new mRNA-based vaccine developments against other pathogens."
- bitL 4y ago
  "Since Fc-mediated effector function could be critical for viral clearance, an increase in IgG4 subclasses might result in longer viral persistence in case of infection."
- phtrivier 4y ago
  Well, it's science because it's the result from a study published in a respected peer reviewed journal. However, it's also "news", because the hypothesis that getting boosted could make you _more_ sick is pretty, well, say, novel. (Hypothesis still to be confirmed, I get it, but if I understand the other comments correctly,that's the jist of it ?) Also, in médecine, pretty much anything that goes into the direction of "more sick people" is, well, "bad" news ? Again, maybe there is a silver lining here, and I don't know enough about the topic. Or maybe it's just a "Burn After Reading" thing. "I guess we learned not to do it again" ? (except, no, we'll have to do it again, and FSM knows what would have happened if...) [1] https://youtu.be/SlA9hmrC8DU https://youtu.be/SlA9hmrC8DU
  - busymom0 4y ago
    The flu shots have shown a similar problem during the 2009 pandemic which was first thought to be happening only in Canada but was later on confirmed in other countries too and also confirmed in ferrets > "seasonal flu vaccination almost doubled the risk of infection with pandemic flu": https://www.cbc.ca/news/health/flu-vaccine-paradox-adds-to-public-health-debate-1.2912790 https://www.cbc.ca/news/health/flu-vaccine-paradox-adds-to-p... > "Canadian researchers noticed in the early weeks of the pandemic that people who got a flu shot for the 2008-2009 winter seemed to be more likely to get infected with the pandemic virus than people who hadn't received a flu shot." > The ferrets in the vaccine group became significantly sicker than the other animals, though all recovered. "The findings that we show are consistent with the increased risk that we saw in the human studies," Ms. Skowronski said. https://www.theglobeandmail.com/life/health-and-fitness/health/flu-shot-issue-may-not-be-canadian-problem-after-all-study/article4530649/ https://www.theglobeandmail.com/life/health-and-fitness/heal...
michaelrpeskin 4y ago
Here's my ELI5 attempt. Disclaimer: the immune system is very complex, even experts really don't understand it as much as we think we do. This is a very simplified view of the system, but I think captures a very large fraction of the story. Let's focus on three types of antibodies - the things your immune system creates in response to a foreign object in your body - for this story: 1) IgM - this is created in your mucosal membranes when you breathe in something foreign. In the context of COVID, we'd expect to find IgM antibodies in people exposed to the virus because the mucosal membranes of the respiratory systems are the first places exposed to a respiratory virus. 2) IgG3 - this is created in your blood and is the main killer of a foreign object. This is what you think of when your immune system is fighting a virus. It also drives the inflammation which is what you generally recognize as the "flu-like symptoms". 3) IgG4 - this is created in response to what we recognize as allergens. For example, if you breathe in a bunch of pollen in the spring, you may have an IgG3 response and feel terrible. Or you body may recognize that that foreign object really isn't a big deal. In this case it will create IgG4 which basically tells your body to ignore the object until it's cleared. It's kind of the opposite of IgG3: rather than ramping up inflammation to fight the object, it's ramps it down and just says "nothing to see here" so you don't waste resources fighting something harmless. What they found is that vaxxed and boosted people have a ton of IgG4 floating around and little to no IgM and IgG3. So what does that mean? Here's where people are going to get spun up because we have to create hypotheses and test them. But even stating some hypotheses will cause the political machine to get mad. 1) IgM is really good at stopping viruses early. From this we'd expect that unvaxxed people exposed to COVID to be more resistant to future infections because the first exposure will create IgM and the virus will be stopped/attenuated in the nose. I don't know the state of the research on this, but it's a hypothesis to test. 2) IgG4 is a bad thing in the context of a replicating virus. If you have IgG4, it's telling your body to ignore the virus because it's "just an allergen". That's fine for pollen which will be cleared out of your system, but it's bad for a replicating virus because it can replicate unfettered. The hypothesis to test here is if people who are more vaxxed have more (re)infections of COVID. Another thought is that the infection may never go away and flare up occasionally (long COVID?). Again, I don't know the research, we need to test these hypotheses to understand it. But it is one piece of the puzzle and a plausible explanation for this (https://www.medrxiv.org/content/10.1101/2022.12.17.22283625v1.full.pdf https://www.medrxiv.org/content/10.1101/2022.12.17.22283625v...) where we see a nearly linear increase in vaccine doses and COVID infection. Again, these are just hypotheses and we need to test them without getting political about the vaccine. This may also be a plausible explanation for COVID related OAS (Original Antigenic Sin) and ADE (Antibody Dependent Enhancement) that some researchers claim they see. At a minimum we can say that the more vaxxed and boosted a person is, the more "non-standard" (compared to other vaccines) their immune response is, and that's worth further investigation.
carry_bit 4y ago
To the degree it's news, it's not "good" news, but further research is needed to see just how "bad" it is. The concern here is if the worse-case scenario turns out to be true: that the mRNA-based vaccines, and especially the boosters, end up training the immune system to tolerate the infection rather than clear it. That would mean a significant fraction of the population are at risk of outcomes ranging from persistent COVID to death, and becoming breeding grounds for more variants in the process. Hopefully further research rules out that scenario.

ergonaught 4y ago

It isn't news. It's science. "Further investigations are needed to clarify the precise immunological mechanisms driving this response and to evaluate whether an IgG4-driven antibody response affects subsequent viral infections and booster vaccinations. This is not only relevant for potential future vaccine campaigns against SARS-CoV-2, but also for new mRNA-based vaccine developments against other pathogens."

bitL 4y ago
"Since Fc-mediated effector function could be critical for viral clearance, an increase in IgG4 subclasses might result in longer viral persistence in case of infection."
phtrivier 4y ago
Well, it's science because it's the result from a study published in a respected peer reviewed journal. However, it's also "news", because the hypothesis that getting boosted could make you _more_ sick is pretty, well, say, novel. (Hypothesis still to be confirmed, I get it, but if I understand the other comments correctly,that's the jist of it ?) Also, in médecine, pretty much anything that goes into the direction of "more sick people" is, well, "bad" news ? Again, maybe there is a silver lining here, and I don't know enough about the topic. Or maybe it's just a "Burn After Reading" thing. "I guess we learned not to do it again" ? (except, no, we'll have to do it again, and FSM knows what would have happened if...) [1] https://youtu.be/SlA9hmrC8DU https://youtu.be/SlA9hmrC8DU
- busymom0 4y ago
  The flu shots have shown a similar problem during the 2009 pandemic which was first thought to be happening only in Canada but was later on confirmed in other countries too and also confirmed in ferrets > "seasonal flu vaccination almost doubled the risk of infection with pandemic flu": https://www.cbc.ca/news/health/flu-vaccine-paradox-adds-to-public-health-debate-1.2912790 https://www.cbc.ca/news/health/flu-vaccine-paradox-adds-to-p... > "Canadian researchers noticed in the early weeks of the pandemic that people who got a flu shot for the 2008-2009 winter seemed to be more likely to get infected with the pandemic virus than people who hadn't received a flu shot." > The ferrets in the vaccine group became significantly sicker than the other animals, though all recovered. "The findings that we show are consistent with the increased risk that we saw in the human studies," Ms. Skowronski said. https://www.theglobeandmail.com/life/health-and-fitness/health/flu-shot-issue-may-not-be-canadian-problem-after-all-study/article4530649/ https://www.theglobeandmail.com/life/health-and-fitness/heal...

michaelrpeskin 4y ago

Here's my ELI5 attempt. Disclaimer: the immune system is very complex, even experts really don't understand it as much as we think we do. This is a very simplified view of the system, but I think captures a very large fraction of the story. Let's focus on three types of antibodies - the things your immune system creates in response to a foreign object in your body - for this story: 1) IgM - this is created in your mucosal membranes when you breathe in something foreign. In the context of COVID, we'd expect to find IgM antibodies in people exposed to the virus because the mucosal membranes of the respiratory systems are the first places exposed to a respiratory virus. 2) IgG3 - this is created in your blood and is the main killer of a foreign object. This is what you think of when your immune system is fighting a virus. It also drives the inflammation which is what you generally recognize as the "flu-like symptoms". 3) IgG4 - this is created in response to what we recognize as allergens. For example, if you breathe in a bunch of pollen in the spring, you may have an IgG3 response and feel terrible. Or you body may recognize that that foreign object really isn't a big deal. In this case it will create IgG4 which basically tells your body to ignore the object until it's cleared. It's kind of the opposite of IgG3: rather than ramping up inflammation to fight the object, it's ramps it down and just says "nothing to see here" so you don't waste resources fighting something harmless. What they found is that vaxxed and boosted people have a ton of IgG4 floating around and little to no IgM and IgG3. So what does that mean? Here's where people are going to get spun up because we have to create hypotheses and test them. But even stating some hypotheses will cause the political machine to get mad. 1) IgM is really good at stopping viruses early. From this we'd expect that unvaxxed people exposed to COVID to be more resistant to future infections because the first exposure will create IgM and the virus will be stopped/attenuated in the nose. I don't know the state of the research on this, but it's a hypothesis to test. 2) IgG4 is a bad thing in the context of a replicating virus. If you have IgG4, it's telling your body to ignore the virus because it's "just an allergen". That's fine for pollen which will be cleared out of your system, but it's bad for a replicating virus because it can replicate unfettered. The hypothesis to test here is if people who are more vaxxed have more (re)infections of COVID. Another thought is that the infection may never go away and flare up occasionally (long COVID?). Again, I don't know the research, we need to test these hypotheses to understand it. But it is one piece of the puzzle and a plausible explanation for this (https://www.medrxiv.org/content/10.1101/2022.12.17.22283625v1.full.pdf https://www.medrxiv.org/content/10.1101/2022.12.17.22283625v...) where we see a nearly linear increase in vaccine doses and COVID infection. Again, these are just hypotheses and we need to test them without getting political about the vaccine. This may also be a plausible explanation for COVID related OAS (Original Antigenic Sin) and ADE (Antibody Dependent Enhancement) that some researchers claim they see. At a minimum we can say that the more vaxxed and boosted a person is, the more "non-standard" (compared to other vaccines) their immune response is, and that's worth further investigation.

carry_bit 4y ago

To the degree it's news, it's not "good" news, but further research is needed to see just how "bad" it is. The concern here is if the worse-case scenario turns out to be true: that the mRNA-based vaccines, and especially the boosters, end up training the immune system to tolerate the infection rather than clear it. That would mean a significant fraction of the population are at risk of outcomes ranging from persistent COVID to death, and becoming breeding grounds for more variants in the process. Hopefully further research rules out that scenario.