9 ms·

mRNA vaccines induce higher long-term IgG4 response versus adenovirus vaccines

38 points by VagueMag 4y ago

thinking4real 4y ago
[flagged]
- londons_explore 4y ago
  Nah - I think as you use phrases like "better than", it's allowed.
  - CrazyPyroLinux 4y ago
    Counterexample 1: "Immunity from infection is 'better than' an experimental shot." Counterexample 2: "The odds of this being a lab origin are 'better than' those of a furin cleavage site evolving naturally." Both are/were cancellable.
    - lilsoso 4y ago
      You've been downvoted into greyed out territory, so those observations aren't tolerated here.
      - CrazyPyroLinux 4y ago
        Right; self-proving point. Also notice I wasn't even espousing them as fact in this context, just providing examples of things one isn't allowed to say.
        true_religion 4y ago
        At the cost of my own karma, let me tell you why. This entire thread is a digression from the articles topic, and meanders around the well worn parts of a contentious political talking point. It serves no purpose. You shouldn’t have responded to the OP. No one should have responded to you, and I should have also left this piece of old flame bait alone. We aren’t supposed to have pointless arguments and I insightful snark. We are supposed to bring up tangents only if we have something new to add.
        TechBro8615 4y ago
        I agree with you, but I think it's fine to continue commenting on these threads once they've been flagged, because at that point only people who opt into [showdead] will be able to see them.
        slaw 4y ago
        It's better than before. Your comment is only downvoted, not dead or account banned.
    - thinking4real 4y ago
      Lol you were greyed out not even for arguing what you’re saying, but simply for giving two examples of what isn’t allowed to be said. Speaks volumes.
- CrazyPyroLinux 4y ago
  [flagged]
- CrazyPyroLinux 4y ago
  On a separate note, this paper doesn't seem to mention any "negative aspects of the vaccine" - It seems to be concluding that [the likes of AstraZeneca etc. perform better on some measures than the mRNA favorites.] edit: I previously stated the conclusion backwards.
  - VagueMag 4y ago
    Not necessarily, IgG4 is a unique case: > In a setting of HIV vaccination, a study compared repeated immunizations with two related HIV vaccine formats. The authors described that the protection of one vaccine composition correlated with the induction of IgG1 and IgG3 Abs, whereas the other vaccine composition hardly showed any protection, which correlated with the generation of IgG4 upon repeated immunizations instead.
    - CrazyPyroLinux 4y ago
      edited; thanks
  - TechBro8615 4y ago
    Why is higher long-term IgG4 response favorable?
CharlesW 4y ago
Full title: "mRNA vaccines against SARS-CoV-2 induce comparably low long-term IgG Fc galactosylation and sialylation levels but increasing long-term IgG4 responses compared to an adenovirus-based vaccine"
pcbro141 4y ago
tangent: but are any of you still getting boosters? Like 4th, 5th shots and stuff. Seems a lot of people gave up after the 3rd shot (1st booster).
- boplicity 4y ago
  Of course -- why wouldn't I? They're free, effective, and extremely low risk.
  - msandford 4y ago
    Man I sure wish I shared your certainty on the subject. It would make my life a lot easier.
    - boplicity 4y ago
      I'm sure you're certain about quite a few things -- you just probably don't spend time thinking about them, hence them not "registering" as things you're certain about.
  - latchkey 4y ago
    I've just been lazy to get the 4th, but I don't have any reason not to. I also haven't had covid yet (that I know of), so whatever I've been doing these last few years seems to have been working (primarily, I just wear a mask in enclosed public spaces). I've noticed that there is a lot of anti-vax stuff surfacing on Twitter recently though (thanks Elon!), so maybe that is where the OP's comment is coming from. For example: https://twitter.com/KariLake/status/1614876088081211392 https://twitter.com/KariLake/status/1614876088081211392 and the correct response (from Aug 2021): https://twitter.com/BadVaccineTakes/status/1425803502274629639 https://twitter.com/BadVaccineTakes/status/14258035022746296...
  - PathOfEclipse 4y ago
    Nothing is free. Some things are just paid for in other ways like taxes, debt, and inflation. Also, I know zero people personally who've been seeiously affected by COVID. However,I personally know one pro vaccine person who was hospitalized by a heart attack immediately after his third shot. To date there has only been a single prospective study on post vaccination myocarditis: https://www.mdpi.com/2414-6366/7/8/196 https://www.mdpi.com/2414-6366/7/8/196 The study estimates that risk of myocarditis is much, much higher than previously reported. We simply don't have the data because reporting has not been stringent and no one is doing the appropriate research: https://youtu.be/2mWZY6vmdBM https://youtu.be/2mWZY6vmdBM
cnnrjcbsn 4y ago
Can someone ELI5 the implications of this please?
- jaywalk 4y ago
  IgG4 response is how your body would typically treat things like allergens that are basically harmless and don't need a full immune response. Covid needs a full immune response, and an IgG4 response suppresses that. You don't want your body to treat a virus the same way it treats pollen.
- jyscao 4y ago
  IgG4 is the class of immunoglobulin responsible for shifting immune response upon encountering some antigen from attack to tolerance, which is good for false positive pathogens like flower pollen that cause seasonal allergies. But that's of course not the type of response one would want from their immune system when encountering SARS-COV-2, since if the viral particles are being tolerated as opposed to being cleared by one's immune system, it leaves the viruses uninhibited to multiply and continuously damage your body.
- fidgewidge 4y ago
  The others did a good job of the technical details. The higher level implication is that taking too many of the shots will appear to make you feel better in the short term but create long term internal damage, as the immune system won't fight the virus as effectively/at all and instead will let it get on with replicating. So it seems the shots convert short term but temporary unpleasantness into long term serious problems - at which point, of course, they will be classed as not vaccine related because they didn't happen immediately. As such the social implications of this discovery are more of the same. The population will continue to be split into camps that think all vaccines are perfect and reject any link with bad outcomes as not proven, denied by public health so it must be false. Public health bodies will continue refusing to break down incidence data by vaccine status, or will do so in fudged ways by redefining what "vaccinated" means. Other people will observe long term disparate outcomes between people who had lots of shots and others who had none, but if they try to speak about what they see they'll be shut down, told it's just anecdotes and not data and maybe fired. Polarization will continue to spiral. Overall: this finding is bad, and the long term implications are bad.
charlie0 4y ago
Can someone explain this in plain English?
- madman2890 4y ago
  This part means that natural immunity outperforms vaccine immunity in protecting against reinfection and spread of COVID-19 over time. " Discussion Our study shows that the mRNA-containing LNP vaccines BNT162b2 and mRNA-1273 induce high anti-S1 IgG and IgA levels in the blood as well as in the saliva, but these Ig levels steadily decrease over time and approach levels that are comparable to the long-term levels induced by two immunizations with the adenovirus-based vaccine AZD1222. In the long run, such pronounced anti-S1 IgG and (s)IgA reductions in the saliva likely reflect the declining protection against infection and from spreading in the respiratory tract of naïve individuals (16, 17). On the other hand, the observed stronger anti-S1 (s)IgA response in the saliva of previously infected vaccinees – likely generated by re-activation of infection-induced local (s)IgA+ memory B cells – might explain their recently described higher protection from infection and spreading " These sections indicate that natural immunity is more effective at preventing infection and spread of COVID-19 than vaccines. "In summary, the data indicate that the high initial mRNA vaccine-induced anti-S1 IgG(1) and IgA responses decrease over time and approach levels induced with the adenovirus-based vaccine up to day 270. Higher and more stable anti-S1 (s)IgA levels in the saliva of pre-infected vaccinees might explain their higher protection from infection and spread of SARS-CoV-2. Intriguingly, the mRNA vaccines, and in particular the mRNA-1273 vaccine, induced increasing long-term anti-S1 serum IgG4 levels in naïve individuals with hitherto unclear influences on the fight against the pathogen. Naïve individuals vaccinated with the adenovirus-based vaccine did not show such long-term anti-S1 IgG4 response at least after two vaccinations until day 270. "
Nomentatus 4y ago
tangent: I've been saying for some time: "What about a live vaccine?" Meaning an killed-virus version of COVID-19, not an adenovirus with additions. A killed vaccine would present all the proteins and give much better immunity. But now the answer occurs to me: that's what Omicron and Krakus are doing, too. By now we've all been infected and reinfected, giving us all the value a killed-virus vaccine would have. You get the RNA vaccine, then mild Omicron that doesn't kill, then mild Krakus that doesn't kill; and then you're as well protected as by getting the killed-virus vaccine, which just takes too long to create. So maybe the real question posed by this study is, does a subsequent infection by Omicron reverse the toleration induced over time by the RNA?
- pfg 4y ago
  Inactivated COVID-19 vaccines (that is, vaccines using virus copies that have been killed - live vaccines would be ones where the virus has been weakened) have been a thing for some time. IIRC China used a lot of them. My understanding is that they're not quite as good as mRNA in terms of efficacy (though I haven't looked this up in some time.)
moistly 4y ago
[flagged]
- LargoLasskhyfv 4y ago
  It's grotesque to deny the possibility that you're part of one big not even beta-, but alpha-A/B/C../X/Y/Z-test. That aside, are the countless threads about bloat, insecurity, technical debt in software here counterproductive, too? Because that's just the way 'commercial reality' created by entrenched players is?
- thunky 4y ago
  Just don't click on the links.
- VagueMag 4y ago
  tl;dr: please protect me from the severe cognitive dissonance these posts are causing me
- archagon 4y ago
  Agreed. What's the point of these threads? It's just a bunch of people grinding axes. Over the last year, I've rarely seen anything other than misinformation and vitriol come out of them. dang said this about moderation: > The idea is not to maintain a centrist position, it's to try to keep the community from wrecking itself via ideological fracture. These threads seem like a prime vector of ideological fracture. (And may result in people making poor medical decisions to boot.)
  - moistly 4y ago
    It’d be fine if the threads were centrist. The problem is with the lying, the FUD, the statements than run absolutely counter to factual truth. HN is going to be harmed by the people who do this, because they are going to go do the same thing in other threads. The quality of discourse on HN is going to suffer greatly.

38 points by VagueMag 4y ago

thinking4real 4y ago

[flagged]

londons_explore 4y ago
Nah - I think as you use phrases like "better than", it's allowed.
- CrazyPyroLinux 4y ago
  Counterexample 1: "Immunity from infection is 'better than' an experimental shot." Counterexample 2: "The odds of this being a lab origin are 'better than' those of a furin cleavage site evolving naturally." Both are/were cancellable.
  - lilsoso 4y ago
    You've been downvoted into greyed out territory, so those observations aren't tolerated here.
    - CrazyPyroLinux 4y ago
      Right; self-proving point. Also notice I wasn't even espousing them as fact in this context, just providing examples of things one isn't allowed to say.
      - true_religion 4y ago
        At the cost of my own karma, let me tell you why. This entire thread is a digression from the articles topic, and meanders around the well worn parts of a contentious political talking point. It serves no purpose. You shouldn’t have responded to the OP. No one should have responded to you, and I should have also left this piece of old flame bait alone. We aren’t supposed to have pointless arguments and I insightful snark. We are supposed to bring up tangents only if we have something new to add.
        TechBro8615 4y ago
        I agree with you, but I think it's fine to continue commenting on these threads once they've been flagged, because at that point only people who opt into [showdead] will be able to see them.
      - slaw 4y ago
        It's better than before. Your comment is only downvoted, not dead or account banned.
  - thinking4real 4y ago
    Lol you were greyed out not even for arguing what you’re saying, but simply for giving two examples of what isn’t allowed to be said. Speaks volumes.
CrazyPyroLinux 4y ago
[flagged]
CrazyPyroLinux 4y ago
On a separate note, this paper doesn't seem to mention any "negative aspects of the vaccine" - It seems to be concluding that [the likes of AstraZeneca etc. perform better on some measures than the mRNA favorites.] edit: I previously stated the conclusion backwards.
- VagueMag 4y ago
  Not necessarily, IgG4 is a unique case: > In a setting of HIV vaccination, a study compared repeated immunizations with two related HIV vaccine formats. The authors described that the protection of one vaccine composition correlated with the induction of IgG1 and IgG3 Abs, whereas the other vaccine composition hardly showed any protection, which correlated with the generation of IgG4 upon repeated immunizations instead.
  - CrazyPyroLinux 4y ago
    edited; thanks
- TechBro8615 4y ago
  Why is higher long-term IgG4 response favorable?

CharlesW 4y ago

Full title: "mRNA vaccines against SARS-CoV-2 induce comparably low long-term IgG Fc galactosylation and sialylation levels but increasing long-term IgG4 responses compared to an adenovirus-based vaccine"

pcbro141 4y ago

tangent: but are any of you still getting boosters? Like 4th, 5th shots and stuff. Seems a lot of people gave up after the 3rd shot (1st booster).

boplicity 4y ago
Of course -- why wouldn't I? They're free, effective, and extremely low risk.
- msandford 4y ago
  Man I sure wish I shared your certainty on the subject. It would make my life a lot easier.
  - boplicity 4y ago
    I'm sure you're certain about quite a few things -- you just probably don't spend time thinking about them, hence them not "registering" as things you're certain about.
- latchkey 4y ago
  I've just been lazy to get the 4th, but I don't have any reason not to. I also haven't had covid yet (that I know of), so whatever I've been doing these last few years seems to have been working (primarily, I just wear a mask in enclosed public spaces). I've noticed that there is a lot of anti-vax stuff surfacing on Twitter recently though (thanks Elon!), so maybe that is where the OP's comment is coming from. For example: https://twitter.com/KariLake/status/1614876088081211392 https://twitter.com/KariLake/status/1614876088081211392 and the correct response (from Aug 2021): https://twitter.com/BadVaccineTakes/status/1425803502274629639 https://twitter.com/BadVaccineTakes/status/14258035022746296...
- PathOfEclipse 4y ago
  Nothing is free. Some things are just paid for in other ways like taxes, debt, and inflation. Also, I know zero people personally who've been seeiously affected by COVID. However,I personally know one pro vaccine person who was hospitalized by a heart attack immediately after his third shot. To date there has only been a single prospective study on post vaccination myocarditis: https://www.mdpi.com/2414-6366/7/8/196 https://www.mdpi.com/2414-6366/7/8/196 The study estimates that risk of myocarditis is much, much higher than previously reported. We simply don't have the data because reporting has not been stringent and no one is doing the appropriate research: https://youtu.be/2mWZY6vmdBM https://youtu.be/2mWZY6vmdBM

cnnrjcbsn 4y ago

Can someone ELI5 the implications of this please?

jaywalk 4y ago
IgG4 response is how your body would typically treat things like allergens that are basically harmless and don't need a full immune response. Covid needs a full immune response, and an IgG4 response suppresses that. You don't want your body to treat a virus the same way it treats pollen.
jyscao 4y ago
IgG4 is the class of immunoglobulin responsible for shifting immune response upon encountering some antigen from attack to tolerance, which is good for false positive pathogens like flower pollen that cause seasonal allergies. But that's of course not the type of response one would want from their immune system when encountering SARS-COV-2, since if the viral particles are being tolerated as opposed to being cleared by one's immune system, it leaves the viruses uninhibited to multiply and continuously damage your body.
fidgewidge 4y ago
The others did a good job of the technical details. The higher level implication is that taking too many of the shots will appear to make you feel better in the short term but create long term internal damage, as the immune system won't fight the virus as effectively/at all and instead will let it get on with replicating. So it seems the shots convert short term but temporary unpleasantness into long term serious problems - at which point, of course, they will be classed as not vaccine related because they didn't happen immediately. As such the social implications of this discovery are more of the same. The population will continue to be split into camps that think all vaccines are perfect and reject any link with bad outcomes as not proven, denied by public health so it must be false. Public health bodies will continue refusing to break down incidence data by vaccine status, or will do so in fudged ways by redefining what "vaccinated" means. Other people will observe long term disparate outcomes between people who had lots of shots and others who had none, but if they try to speak about what they see they'll be shut down, told it's just anecdotes and not data and maybe fired. Polarization will continue to spiral. Overall: this finding is bad, and the long term implications are bad.

charlie0 4y ago

Can someone explain this in plain English?

madman2890 4y ago
This part means that natural immunity outperforms vaccine immunity in protecting against reinfection and spread of COVID-19 over time. " Discussion Our study shows that the mRNA-containing LNP vaccines BNT162b2 and mRNA-1273 induce high anti-S1 IgG and IgA levels in the blood as well as in the saliva, but these Ig levels steadily decrease over time and approach levels that are comparable to the long-term levels induced by two immunizations with the adenovirus-based vaccine AZD1222. In the long run, such pronounced anti-S1 IgG and (s)IgA reductions in the saliva likely reflect the declining protection against infection and from spreading in the respiratory tract of naïve individuals (16, 17). On the other hand, the observed stronger anti-S1 (s)IgA response in the saliva of previously infected vaccinees – likely generated by re-activation of infection-induced local (s)IgA+ memory B cells – might explain their recently described higher protection from infection and spreading " These sections indicate that natural immunity is more effective at preventing infection and spread of COVID-19 than vaccines. "In summary, the data indicate that the high initial mRNA vaccine-induced anti-S1 IgG(1) and IgA responses decrease over time and approach levels induced with the adenovirus-based vaccine up to day 270. Higher and more stable anti-S1 (s)IgA levels in the saliva of pre-infected vaccinees might explain their higher protection from infection and spread of SARS-CoV-2. Intriguingly, the mRNA vaccines, and in particular the mRNA-1273 vaccine, induced increasing long-term anti-S1 serum IgG4 levels in naïve individuals with hitherto unclear influences on the fight against the pathogen. Naïve individuals vaccinated with the adenovirus-based vaccine did not show such long-term anti-S1 IgG4 response at least after two vaccinations until day 270. "

Nomentatus 4y ago

tangent: I've been saying for some time: "What about a live vaccine?" Meaning an killed-virus version of COVID-19, not an adenovirus with additions. A killed vaccine would present all the proteins and give much better immunity. But now the answer occurs to me: that's what Omicron and Krakus are doing, too. By now we've all been infected and reinfected, giving us all the value a killed-virus vaccine would have. You get the RNA vaccine, then mild Omicron that doesn't kill, then mild Krakus that doesn't kill; and then you're as well protected as by getting the killed-virus vaccine, which just takes too long to create. So maybe the real question posed by this study is, does a subsequent infection by Omicron reverse the toleration induced over time by the RNA?

pfg 4y ago
Inactivated COVID-19 vaccines (that is, vaccines using virus copies that have been killed - live vaccines would be ones where the virus has been weakened) have been a thing for some time. IIRC China used a lot of them. My understanding is that they're not quite as good as mRNA in terms of efficacy (though I haven't looked this up in some time.)

moistly 4y ago

[flagged]

LargoLasskhyfv 4y ago
It's grotesque to deny the possibility that you're part of one big not even beta-, but alpha-A/B/C../X/Y/Z-test. That aside, are the countless threads about bloat, insecurity, technical debt in software here counterproductive, too? Because that's just the way 'commercial reality' created by entrenched players is?
thunky 4y ago
Just don't click on the links.
VagueMag 4y ago
tl;dr: please protect me from the severe cognitive dissonance these posts are causing me
archagon 4y ago
Agreed. What's the point of these threads? It's just a bunch of people grinding axes. Over the last year, I've rarely seen anything other than misinformation and vitriol come out of them. dang said this about moderation: > The idea is not to maintain a centrist position, it's to try to keep the community from wrecking itself via ideological fracture. These threads seem like a prime vector of ideological fracture. (And may result in people making poor medical decisions to boot.)
- moistly 4y ago
  It’d be fine if the threads were centrist. The problem is with the lying, the FUD, the statements than run absolutely counter to factual truth. HN is going to be harmed by the people who do this, because they are going to go do the same thing in other threads. The quality of discourse on HN is going to suffer greatly.