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Does anyone understand why a third dose of the same vaccine improves immunity to Omicron? I'm willing to believe the empirical evidence that boosters make a me

Does anyone understand why a third dose of the same vaccine improves immunity to Omicron? I'm willing to believe the empirical evidence that boosters make a meaningful difference, but I can't figure out intuitively why the same mRNA a third time helps to address this new spike.

eagsalazar2 5y ago
Maybe it is less about it being the 2nd or 3rd shot and more about how recently you received your last shot? I got my 2nd shot 7 months ago and we've already heard that protection fades over time, so maybe the booster just works because it boosts, not because it is really any different than my 2nd shot.
- SideburnsOfDoom 5y ago
  > Maybe is ... about how recently you received your last shot .. not because it is really any different than my 2nd shot. No. That appears not be the situation. Immunity shortly after the thirds shot is substantially higher than shortly after the second https://twitter.com/PaulMainwood/status/1460191035531878405 https://twitter.com/PaulMainwood/status/1460191035531878405 https://twitter.com/PaulMainwood/status/1458026852249919490 https://twitter.com/PaulMainwood/status/1458026852249919490
  - eightysixfour 5y ago
    I have seen speculation that the second dose was given too quickly.
    - xchaotic 5y ago
      Given how quickly the virus mutates, giving it less frequently makes even less sense.
      - eightysixfour 5y ago
        My response was with respect to maximizing immuno response following vaccination. There is some evidence that larger spacing between doses increases response.
    - wlesieutre 5y ago
      I wonder if that's a factor in the Pfizer/BioNTech vs Moderna performance. Moderna had a higher dosage, but it was also 4 weeks between doses instead of 3.
      - SideburnsOfDoom 5y ago
        > but it was also 4 weeks between doses instead of 3. YMMV. The UK gave out AZ and Pfizer. First at a 12 week interval, then shortened to 8 weeks.
    - SideburnsOfDoom 5y ago
      Firstly, YMMV, different people got different separations of different vaccines. The US doing Pfizer 3 weeks apart was the fastest. The UK gave out AZ and Pfizer. First at a 12 week interval, then shortened to 8 weeks The question is: too quickly for what? My understanding is that a) If the goal was optimal immunity in the longer term then yes, it might be overly quick. b) But if the goal was fighting the raging pandemic that needed urgent actions right now as "the house is on fire", and you have a lot of vaccine doses, then no, maybe not too fast. Finally, a lot of vaccine courses require more than 2 doses, separated by more than a couple of months. UK standard childhood vaccination schedule for instance. "Polio" is in there 5 times. Polio is a memory, but only because because to this day they don't mess around with vaccinating against it
      - eightysixfour 5y ago
        Agreed, I was only referencing a.
    - Symmetry 5y ago
      If you assume an unlimited supply of vaccine then the shorter dose interval gets everybody to good level of sterilizing immunity as quickly as possible.
      - SideburnsOfDoom 5y ago
        Yep. if you need to fight against a raging pandemic, then quickly as possible (as quickly as is tested to be safe, quickly as makes a significant difference) is the over-riding concern.
        astrange 5y ago
        That implies we thought about it in the US, but we didn't really, and our public health people seem to be completely inflexible about everything. The schedule we used for vaccines is just what was done for their trials.
        SideburnsOfDoom 5y ago
        > The schedule we used for vaccines is just what was done for their trials. There is a reason for that - what's being deployed is what has been tested. You could work out an optimal schedule, but that might take years of trials, and meanwhile people are dying.
        astrange 5y ago
        Other countries stretched them out and saw positive results.
kgwxd 5y ago
Is it not just timing? I thought the effectiveness of the vaccines only lasted around 6 months. In the US 18+ were able to get it 7 or 8 months ago.
- Retric 5y ago
  Vaccines can last your entire lifetime, but their effectiveness decays over time it largely depends on the disease and your risk of infection. Booster shots for various vaccines have been common for example, it’s recommended people take a Tdap booster every 10 years, Tetanus every 4-6 etc. The flu vaccine is a special case as it’s changed every year.
  - dsmnd 5y ago
    The 'T' in Tdap stands for tetanus
    - Retric 5y ago
      Yes, though to be clear your supposed to get a both. “It is recommended that adults get a Tdap shot for one of their tetanus boosters.” https://www.verywellhealth.com/booster-shots-1298291 https://www.verywellhealth.com/booster-shots-1298291 It simply reduces the number of injections when you get multiple vaccines at the same time.
  - chasil 5y ago
    In the original use of the vaccina virus against variola (smallpox) infection, symptomatic smallpox could present after vaccina exposoure of at least five years past. https://en.wikipedia.org/wiki/Smallpox#Prevention https://en.wikipedia.org/wiki/Smallpox#Prevention "Smallpox vaccination provides a high level of immunity for three to five years and decreasing immunity thereafter. If a person is vaccinated again later, the immunity lasts even longer. Studies of smallpox cases in Europe in the 1950s and 1960s demonstrated that the fatality rate among persons vaccinated less than 10 years before exposure was 1.3 percent; it was 7 percent among those vaccinated 11 to 20 years prior, and 11 percent among those vaccinated 20 or more years before infection. By contrast, 52 percent of unvaccinated persons died."
sdeframond 5y ago
In other industries they call this "sales": getting rid of current perishable stock before buying fresh one. It's there, we might as well use it.
- eagsalazar2 5y ago
  You really think the CDC and other govt and NGO organizations, as an international coordinated group effort, are in bed with pharma companies, plotting with them to falsify data and craft false recommendations, just so those farma companies can make more $$? I mean, I actually do think that pharma companies are vile, have successfully gained significant regulatory capture, and can influence policy through their own messaging and lobbying, but this wouldn't be influence, this would be coordinated and crafted disinformation across many many parties, most of whom don't work for pharma at all. Honestly this theory seems like absolute crazy talk. Especially when perfectly reasonable explanations exist like the fact that immunity from vaccines wanes over time. When given option 1 (crazy, complicated, far fetched, zero evidence) and option 2 (simple, makes sense, lots of independent scientific parties agreeing), and you pick options 2... ???? I'm confused about how you pick #1.
  - sdeframond 5y ago
    I just think we would rather use the doses already produced before they spoil than wait for the new ones.
  - DwnVoteHoneyPot 5y ago
    Big Pharma mobilized an armies of people and equipment to create vaccines in record time to save lives, but people still like to shit on them.
  - throwawayacc2 5y ago
    > You really think the CDC and other govt and NGO organizations, as an international coordinated group effort, are in bed with pharma companies, plotting with them to craft false recommendations, just so those farma companies can make more $$? Yes.
ufo 5y ago
One of the theories is that the booster raises the levels of neutralizing antibodies. While the antibodies against the original strain don't work as well against Omicron, having more of them does help.
afterburner 5y ago
Because of the way your immune system works. Vaccines aren't medicine, they work by provoking an immune response. What happens after that immune response is triggered is way more complicated than just "molecule X get response Y", there are multiple stages of responses, and the deeper, longer span ones create a resilience against mutations as well. It is extremely common for a proper vaccination regimen to require multiple doses, and it has entirely to do with how the immune system works.
- deleted 5y ago
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deleted 5y ago
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deleted 5y ago
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Symmetry 5y ago
After exposure to a pathogen the levels your body starts evolving antibodies against it. It also quickly ramps up antibody production, but ramps that down over time without additional exposure. Having had a more recent jab will mean a higher quantities of antibodies. But more vaccinations also means your body has done more cycles of evolving better targeted antibodies against the threat. I assume that there's a certain level of diminishing return to the second factor, as well as questions about how much the extra work translates against a new variant. But the second effect exists alongside the first.
hackerfromthefu 5y ago
And no one is talking about whether we will be expected to take a fourth and subsequent
- SideburnsOfDoom 5y ago
  No-one really knows that yet. Novel virus is new. If I had to guess, I would expect another anti-COVID jab in 2022. I expect 1 injection in 2022, maybe in autumn, of a mRNA vaccine, against a strain such as Omicron, that is not original COVID-19-alpha. Not a firm prediction, just a guess at what's IMHO most likely.
SubiculumCode 5y ago
I am not an immunologist, but I imagine repeated infection is a signal to the body to build and expand immunity to the virus.
Retric 5y ago
Mutations in spike proteins don’t completely change it’s shape so they render a percentage of antibodies infective vs that specific strain. A boosted immune response can therefore be less efficient but still useful. To simplify, Vaccines provide long term protection because the immune system builds infrastructure to rapidly create antibodies after infection cutting days off of the immune response. That’s huge because the virus has less time to replicate in your body. Vaccines use multiple injections to increase how much infrastructure is built and the number of types of antibodies being produced. Also this infrastructure decays over time if you never see the strain again. However, in the short term your body reacts like it’s infected actually flooding the body with the appropriate antibodies. This isn’t sustainable but can crush most infections before they go anywhere. Kind of a bonus turbo mode which can be really helpful if your say going to treat people infected with the disease.
SideburnsOfDoom 5y ago
> Does anyone understand why a third dose of the same vaccine improves immunity to Omicron? From what I've read, 2 doses in 8-12 weeks is a small separation, as these things go. A third dose 6 months after the second is not just a third revision of the lesson (metaphorically), but a more appropriate spacing to re-enforce it.
thinkharderdev 5y ago
From what I understand it is about affinity maturation. Basically, when you get an initial vaccine (or infection) your immune system learns how to recognize the antigen (the virus spike protein) and produces a bunch of antibodies to recognize it. But your immune system also preserves the spike protein in antigen presenting cells so it can continue to produce antibodies to recognize more features of the spike protein. Over time, your immune system learns how to produce a broader range of antibodies that are (in aggregate) more likely to recognize partially mutated versions of the antigen. That's the affinity maturation part. So when you get a booster (or a breakthrough infection) your immune system kicks into gear again but now it produces a broader range of antibodies. In addition the number of antibodies produced from the booster is quantitatively much larger than from the first vaccine. So with a booster you end up with more antibodies but also a larger variety of antibodies that can recognize different features of the spike protein (including features that are consistent between variants). That's my understand at least but I am not an immunologist.
- corin_ 5y ago
  > So when you get a booster (or a breakthrough infection) your immune system kicks into gear again but now it produces a broader range of antibodies. Would/could it not also be the case for exposure to the virus that doesn't result in a breakthrough infection i.e. the body detects it and fights it off successfully? (I daresay you didn't mean to imply that, just checking.)
  - thinkharderdev 5y ago
    I would assume so but it probably depends on the "level" of exposure and such.
notabee 5y ago
From what I understand, the immune system has some capacity to anticipate mutations. The most basic function of antibodies is to stick to and neutralize the target, in this case the spike protein that the mRNA vaccine presents to the immune system via producing some copies in muscle cells. But the immune system doesn't just produce exact form-fitting duplicate antibodies, it also has something like a biological "fuzzer" that also produces antibodies to target anticipated mutations to its main target, the spike protein. Each time this system gets stimulated, it not only makes more antibodies and more memory cells to produce them, it also runs some more anticipatory mutations. So in aggregate, hopefully the increased quantity plus maturation of these various antibody tweaks produce enough antibodies that stick well enough to the virus to incapacitate or slow it down so that the other aspects of the immune system have time to react instead of getting overwhelmed. And it makes sense to have an antibody arms race like this since viruses mutate so fast. Obviously, this doesn't always work and viruses frequently out-mutate the immune memory, but the immune system is pretty smart. By the way, if there are any actual scientists here that spot some atrocious mistake I've made describing this, please let me know. I find it really interesting to learn about but I'm certainly no expert.
- lborsato 5y ago
  Unfortunately as a result of original antigenic sin, the fact that the immune system has been trained for by a vaccine for a certain strain means that the body will respond to that strain, likely unable to mount a new defence for the different strain. https://pubmed.ncbi.nlm.nih.gov/33692194/ https://pubmed.ncbi.nlm.nih.gov/33692194/
  - freemint 5y ago
    Virologist are aware of this but I seen no indication that it applies to the CoVi variants we are currently dealing with.
pa7x1 5y ago
The CEO of BioNTech said they don't know for sure but speculated that memory B cells may keep hypermutating after a third shot which could result in the improved effectiveness against Omicron. Or that's what I understood with my very rudimentary knowledge of biology.

eagsalazar2 5y ago

Maybe it is less about it being the 2nd or 3rd shot and more about how recently you received your last shot? I got my 2nd shot 7 months ago and we've already heard that protection fades over time, so maybe the booster just works because it boosts, not because it is really any different than my 2nd shot.

SideburnsOfDoom 5y ago
> Maybe is ... about how recently you received your last shot .. not because it is really any different than my 2nd shot. No. That appears not be the situation. Immunity shortly after the thirds shot is substantially higher than shortly after the second https://twitter.com/PaulMainwood/status/1460191035531878405 https://twitter.com/PaulMainwood/status/1460191035531878405 https://twitter.com/PaulMainwood/status/1458026852249919490 https://twitter.com/PaulMainwood/status/1458026852249919490
- eightysixfour 5y ago
  I have seen speculation that the second dose was given too quickly.
  - xchaotic 5y ago
    Given how quickly the virus mutates, giving it less frequently makes even less sense.
    - eightysixfour 5y ago
      My response was with respect to maximizing immuno response following vaccination. There is some evidence that larger spacing between doses increases response.
  - wlesieutre 5y ago
    I wonder if that's a factor in the Pfizer/BioNTech vs Moderna performance. Moderna had a higher dosage, but it was also 4 weeks between doses instead of 3.
    - SideburnsOfDoom 5y ago
      > but it was also 4 weeks between doses instead of 3. YMMV. The UK gave out AZ and Pfizer. First at a 12 week interval, then shortened to 8 weeks.
  - SideburnsOfDoom 5y ago
    Firstly, YMMV, different people got different separations of different vaccines. The US doing Pfizer 3 weeks apart was the fastest. The UK gave out AZ and Pfizer. First at a 12 week interval, then shortened to 8 weeks The question is: too quickly for what? My understanding is that a) If the goal was optimal immunity in the longer term then yes, it might be overly quick. b) But if the goal was fighting the raging pandemic that needed urgent actions right now as "the house is on fire", and you have a lot of vaccine doses, then no, maybe not too fast. Finally, a lot of vaccine courses require more than 2 doses, separated by more than a couple of months. UK standard childhood vaccination schedule for instance. "Polio" is in there 5 times. Polio is a memory, but only because because to this day they don't mess around with vaccinating against it
    - eightysixfour 5y ago
      Agreed, I was only referencing a.
  - Symmetry 5y ago
    If you assume an unlimited supply of vaccine then the shorter dose interval gets everybody to good level of sterilizing immunity as quickly as possible.
    - SideburnsOfDoom 5y ago
      Yep. if you need to fight against a raging pandemic, then quickly as possible (as quickly as is tested to be safe, quickly as makes a significant difference) is the over-riding concern.
      - astrange 5y ago
        That implies we thought about it in the US, but we didn't really, and our public health people seem to be completely inflexible about everything. The schedule we used for vaccines is just what was done for their trials.
        SideburnsOfDoom 5y ago
        > The schedule we used for vaccines is just what was done for their trials. There is a reason for that - what's being deployed is what has been tested. You could work out an optimal schedule, but that might take years of trials, and meanwhile people are dying.
        astrange 5y ago
        Other countries stretched them out and saw positive results.

kgwxd 5y ago

Is it not just timing? I thought the effectiveness of the vaccines only lasted around 6 months. In the US 18+ were able to get it 7 or 8 months ago.

Retric 5y ago
Vaccines can last your entire lifetime, but their effectiveness decays over time it largely depends on the disease and your risk of infection. Booster shots for various vaccines have been common for example, it’s recommended people take a Tdap booster every 10 years, Tetanus every 4-6 etc. The flu vaccine is a special case as it’s changed every year.
- dsmnd 5y ago
  The 'T' in Tdap stands for tetanus
  - Retric 5y ago
    Yes, though to be clear your supposed to get a both. “It is recommended that adults get a Tdap shot for one of their tetanus boosters.” https://www.verywellhealth.com/booster-shots-1298291 https://www.verywellhealth.com/booster-shots-1298291 It simply reduces the number of injections when you get multiple vaccines at the same time.
- chasil 5y ago
  In the original use of the vaccina virus against variola (smallpox) infection, symptomatic smallpox could present after vaccina exposoure of at least five years past. https://en.wikipedia.org/wiki/Smallpox#Prevention https://en.wikipedia.org/wiki/Smallpox#Prevention "Smallpox vaccination provides a high level of immunity for three to five years and decreasing immunity thereafter. If a person is vaccinated again later, the immunity lasts even longer. Studies of smallpox cases in Europe in the 1950s and 1960s demonstrated that the fatality rate among persons vaccinated less than 10 years before exposure was 1.3 percent; it was 7 percent among those vaccinated 11 to 20 years prior, and 11 percent among those vaccinated 20 or more years before infection. By contrast, 52 percent of unvaccinated persons died."

sdeframond 5y ago

In other industries they call this "sales": getting rid of current perishable stock before buying fresh one. It's there, we might as well use it.

eagsalazar2 5y ago
You really think the CDC and other govt and NGO organizations, as an international coordinated group effort, are in bed with pharma companies, plotting with them to falsify data and craft false recommendations, just so those farma companies can make more $$? I mean, I actually do think that pharma companies are vile, have successfully gained significant regulatory capture, and can influence policy through their own messaging and lobbying, but this wouldn't be influence, this would be coordinated and crafted disinformation across many many parties, most of whom don't work for pharma at all. Honestly this theory seems like absolute crazy talk. Especially when perfectly reasonable explanations exist like the fact that immunity from vaccines wanes over time. When given option 1 (crazy, complicated, far fetched, zero evidence) and option 2 (simple, makes sense, lots of independent scientific parties agreeing), and you pick options 2... ???? I'm confused about how you pick #1.
- sdeframond 5y ago
  I just think we would rather use the doses already produced before they spoil than wait for the new ones.
- DwnVoteHoneyPot 5y ago
  Big Pharma mobilized an armies of people and equipment to create vaccines in record time to save lives, but people still like to shit on them.
- throwawayacc2 5y ago
  > You really think the CDC and other govt and NGO organizations, as an international coordinated group effort, are in bed with pharma companies, plotting with them to craft false recommendations, just so those farma companies can make more $$? Yes.

ufo 5y ago

One of the theories is that the booster raises the levels of neutralizing antibodies. While the antibodies against the original strain don't work as well against Omicron, having more of them does help.

afterburner 5y ago

Because of the way your immune system works. Vaccines aren't medicine, they work by provoking an immune response. What happens after that immune response is triggered is way more complicated than just "molecule X get response Y", there are multiple stages of responses, and the deeper, longer span ones create a resilience against mutations as well. It is extremely common for a proper vaccination regimen to require multiple doses, and it has entirely to do with how the immune system works.

deleted 5y ago
[deleted]

deleted 5y ago

[deleted]

deleted 5y ago

[deleted]

Symmetry 5y ago

After exposure to a pathogen the levels your body starts evolving antibodies against it. It also quickly ramps up antibody production, but ramps that down over time without additional exposure. Having had a more recent jab will mean a higher quantities of antibodies. But more vaccinations also means your body has done more cycles of evolving better targeted antibodies against the threat. I assume that there's a certain level of diminishing return to the second factor, as well as questions about how much the extra work translates against a new variant. But the second effect exists alongside the first.

hackerfromthefu 5y ago

And no one is talking about whether we will be expected to take a fourth and subsequent

SideburnsOfDoom 5y ago
No-one really knows that yet. Novel virus is new. If I had to guess, I would expect another anti-COVID jab in 2022. I expect 1 injection in 2022, maybe in autumn, of a mRNA vaccine, against a strain such as Omicron, that is not original COVID-19-alpha. Not a firm prediction, just a guess at what's IMHO most likely.

SubiculumCode 5y ago

I am not an immunologist, but I imagine repeated infection is a signal to the body to build and expand immunity to the virus.

Retric 5y ago

Mutations in spike proteins don’t completely change it’s shape so they render a percentage of antibodies infective vs that specific strain. A boosted immune response can therefore be less efficient but still useful. To simplify, Vaccines provide long term protection because the immune system builds infrastructure to rapidly create antibodies after infection cutting days off of the immune response. That’s huge because the virus has less time to replicate in your body. Vaccines use multiple injections to increase how much infrastructure is built and the number of types of antibodies being produced. Also this infrastructure decays over time if you never see the strain again. However, in the short term your body reacts like it’s infected actually flooding the body with the appropriate antibodies. This isn’t sustainable but can crush most infections before they go anywhere. Kind of a bonus turbo mode which can be really helpful if your say going to treat people infected with the disease.

SideburnsOfDoom 5y ago

> Does anyone understand why a third dose of the same vaccine improves immunity to Omicron? From what I've read, 2 doses in 8-12 weeks is a small separation, as these things go. A third dose 6 months after the second is not just a third revision of the lesson (metaphorically), but a more appropriate spacing to re-enforce it.

thinkharderdev 5y ago

From what I understand it is about affinity maturation. Basically, when you get an initial vaccine (or infection) your immune system learns how to recognize the antigen (the virus spike protein) and produces a bunch of antibodies to recognize it. But your immune system also preserves the spike protein in antigen presenting cells so it can continue to produce antibodies to recognize more features of the spike protein. Over time, your immune system learns how to produce a broader range of antibodies that are (in aggregate) more likely to recognize partially mutated versions of the antigen. That's the affinity maturation part. So when you get a booster (or a breakthrough infection) your immune system kicks into gear again but now it produces a broader range of antibodies. In addition the number of antibodies produced from the booster is quantitatively much larger than from the first vaccine. So with a booster you end up with more antibodies but also a larger variety of antibodies that can recognize different features of the spike protein (including features that are consistent between variants). That's my understand at least but I am not an immunologist.

corin_ 5y ago
> So when you get a booster (or a breakthrough infection) your immune system kicks into gear again but now it produces a broader range of antibodies. Would/could it not also be the case for exposure to the virus that doesn't result in a breakthrough infection i.e. the body detects it and fights it off successfully? (I daresay you didn't mean to imply that, just checking.)
- thinkharderdev 5y ago
  I would assume so but it probably depends on the "level" of exposure and such.

notabee 5y ago

From what I understand, the immune system has some capacity to anticipate mutations. The most basic function of antibodies is to stick to and neutralize the target, in this case the spike protein that the mRNA vaccine presents to the immune system via producing some copies in muscle cells. But the immune system doesn't just produce exact form-fitting duplicate antibodies, it also has something like a biological "fuzzer" that also produces antibodies to target anticipated mutations to its main target, the spike protein. Each time this system gets stimulated, it not only makes more antibodies and more memory cells to produce them, it also runs some more anticipatory mutations. So in aggregate, hopefully the increased quantity plus maturation of these various antibody tweaks produce enough antibodies that stick well enough to the virus to incapacitate or slow it down so that the other aspects of the immune system have time to react instead of getting overwhelmed. And it makes sense to have an antibody arms race like this since viruses mutate so fast. Obviously, this doesn't always work and viruses frequently out-mutate the immune memory, but the immune system is pretty smart. By the way, if there are any actual scientists here that spot some atrocious mistake I've made describing this, please let me know. I find it really interesting to learn about but I'm certainly no expert.

lborsato 5y ago
Unfortunately as a result of original antigenic sin, the fact that the immune system has been trained for by a vaccine for a certain strain means that the body will respond to that strain, likely unable to mount a new defence for the different strain. https://pubmed.ncbi.nlm.nih.gov/33692194/ https://pubmed.ncbi.nlm.nih.gov/33692194/
- freemint 5y ago
  Virologist are aware of this but I seen no indication that it applies to the CoVi variants we are currently dealing with.

pa7x1 5y ago

The CEO of BioNTech said they don't know for sure but speculated that memory B cells may keep hypermutating after a third shot which could result in the improved effectiveness against Omicron. Or that's what I understood with my very rudimentary knowledge of biology.