14 ms·

> On the other hand, we report that after pre-exposure to mRNA-LNPs, the resistance of mice to heterologous infections with influenza virus increased while res

by mabbo 4y ago

> On the other hand, we report that after pre-exposure to mRNA-LNPs, the resistance of mice to heterologous infections with influenza virus increased while resistance to Candida albicans decreased. It sounds to me as though the tradeoff being made here is: a slightly decreased immune response generally, but a better immune response to the thing you've been immunized against. That seems to be a reasonable tradeoff if there's something really bad going around. But as they say in the paper summary: more research is needed. Also: this is purely in mice. They have zero data on whether this is true for humans.

sawyna 4y ago
Well, the paper quotes unexpected changes in your adaptive immune response. What's observed is a slight decrease of immune response in mice for a highly specific condition. We don't know how the overall immune response changes. For all you know, small decreases in immune response to diseases might bubble up to be a significant decrease.
lazyier 4y ago
I donno. Seems like white blood cells are kinda important. We have a huge number of interactions with bacteria and viruses and all sorts of microorganisms. Hundreds? Thousands times a day? Scratches in the kitchen while preparing food, for example, floods our body with stuff that white blood cells are required to deal with. Giving up some of the ability to deal with those for a small reduction in the symptoms associated with a specific disease doesn't seem like a useful trade off.
- dangerlibrary 4y ago
  Over a million people, in the U.S. alone, died in under two years after being infected with this virus. Even granting the unlikely possibility that this mouse model is reflective of the immune response in humans, whatever other microorganisms people were encountering were demonstrably less dangerous than SARS-CoV-2. Unless you know of some other highly infectious microorganism that rapidly spread to hundreds of millions of people and killed 1-2% of those it infected?
  - taolegal 4y ago
    > Even granting the genuinely unlikely possibility that this mouse model is reflective of the immune response in humans, whatever other microorganisms people were encountering were demonstrably less dangerous than SARS-CoV-2. The mouse model is apparently enough for the new booster.
    - peter422 4y ago
      So they ran the phase 2/3 trial in >1000 humans for fun? The problem with anti-vaxxers is you just imagine a world in which everything is underhanded and a conspiracy when all the science and data is out there in the open, just ignored.
      - taolegal 4y ago
        Anti-vax? You have no clue what my beliefs are on this, I'm not anti-vaccine. I remember just last year the Biden administration forced through the booster shots (after a propaganda campaign predicated one & done, that then extended into mandates, which Biden, Pelosi & others said were never on the table or illegal, later to be proven unconstitutional by the supreme court). Senior officials at the FDA resigned over the insufficient evidence of efficacy. Not only was it unclear that they should be approved for seniors, they just opened it up to everyone. It's only gotten worse now. It's not even remotely clear to me that the average healthy person (not on the standard American diet, chronically ill with the typical stuff like diabetes & obesity) needs upwards of 4 vaccines, and counting, for a virus that's much more attenuated & practically everyone has some form of immunity at this point. Also: to answer your question, from what I can tell the studies haven't shown efficacy. They only show that antibodies rose, which we know isn't absolute proof of efficacy with regards to infection or disease.
        peter422 4y ago
        I never said the trials showed efficacy, though there are multiple high quality trials which do show serious benefits of 3rd/4th shots in various age groups. I just say they ran human trials, which your comment implied they didn’t. Also: - no good evidence the virus is attenuated (lower hospitalizations/mortality likely driven by increased population immunity) - a lot of FDA/CDC officials agreed with the decision too, and I think on the whole were proved right to offer to the booster to older populations before all the studies were completed. - nobody is forcing you to get the 3rd/4th shots, why do you want to prevent other people from getting them if they want them? You are sooo sure they are bad?
- deleted 4y ago
  [deleted]
- mabbo 4y ago
  But the thing is we ran a massive experiment on this called "The covid-19 pandemic". What we saw was no serious increase in mortality for the immunized, and a significant increase in mortality for the non-immunized. Seems like the data from that experiment should be taken into consideration when deciding if the tradeoff is worthwhile, right?
  - origin_path 4y ago
    Two problems: 1. That wasn't a controlled experiment. Observational data < RCTs. 2. You are mixing up mortality and mortality attributed to COVID. It's a common error. For overall mortality the picture is far less clear. For example in the Pfizer trials there were more deaths overall in the vaccinated arm than the unvaccinated arm i.e. RCT evidence = no mortality benefit. Also, we now have excess deaths above the expected baseline for long periods in 2022, which is unprecedented. Governments are highly reluctant to split these deaths out by vaccine status, but the increase seems mostly attributed to heart and blood clotting related deaths. So the data from the "experiment" is not obviously positive.
    - ttpphd 4y ago
      [flagged]
      - logic_beats_pro 4y ago
        As you see in the article, this is a mathematical model which indicates vaccines saved 20,000,000 lives. It is completely unprovable and only serves as a nice sounding talking point. I also could claim 20,000,000 lives were saved by natural immunity. Or vitamin D from sunshine. Or the placebo effect. All of those mentioned are also not provable.
        blackbear_ 4y ago
        Do you have specific reasons not to believe the model and/or data in that article, beyond "all models are wrong by definition"?
- dragontamer 4y ago
  You're welcome to post the other pandemics that occurred in 2020 through 2022. Flu was practically wiped out for example. COVID19 was more fit, and many people were taking precautions (ie: masks) that also hampered the spread of Flu. If mRNA vaccines really inhibited general immune response to other viruses / bacteria, it should be demonstrable. Just line up the number of people who died / got sick of non-COVID19 diseases in 2020 through 2022 and compare them to the COVID19 vaccine patients, stratified for age/sex/race.
  - zionic 4y ago
    >Just line up the number of people who died / got sick of non-COVID19 diseases in 2020 This is _extremely_ difficult to do, as a mix of both incentive structures and poor policy lead to any death with a positive PCR test being counted as a COVID death. It's practically impossible now to go back and figure out how many were _actually_ "killed by COVID" vs "died _with_ COVID".
    - peter422 4y ago
      Most people who had covid and died probably wouldn’t have died so quickly if they didn’t have covid. Why you do the mental gymnastics to pretend this isn’t true is so baffling.
      - spookthesunset 4y ago
        I’m sure George Floyd would have lived a little longer if he wasn’t Covid positive when he died. It doesn’t matter anyway. The data required to support our mitigations stopped mattering a long long time ago. ..Sometime back when the “4% kill rate” predicted by the imperial college paper turned out to be very very wrong and when all those temporary military hospital things got closed because they weren’t being used. That might have been a good time to reevaluate what the fuck we were doing but instead of celebrating the fact that Covid wasn’t nearly as bad as predicted we just doubled down for a year and a half more instead. Honestly it’s best to just take the numbers at face value and assume any overcount is balanced by undercounts.
- manwe150 4y ago
  As another commented pointed out, we have hundreds of millions of data points in people now post-vaccination and post-boosters, which haven’t detected a problem, and only 12 here in mice, that the authors suggest warrants further study. Which hypothesis are you saying has “no data”?
  - junofan 4y ago
    It took only 12 mice to find unexpected effects? How was the vaccine tested again?
    - Sohcahtoa82 4y ago
      > It took only 12 That's a very small sample size. Also, it's mice.
    - yojo 4y ago
      You’d be amazed at the number of unexpected effects I could find studying just a single mouse! Having a small number data points means that a single outlier can impact your results. And since “no results” typically doesn’t get published, the rare events end up disproportionately represented in journals. The smaller the sample size, the more likely the “effect” you’re seeing is just random chance.
  - FollowingTheDao 4y ago
    It is hard to see a problem if you are not looking for it or if the cause is distant from the reaction. An Example: My friend had undiagnosed alpha gal for months because the anaphylactic reaction happened to him more than 12 hours after eating red meat so they did not know the connection. Is Long Covid actually not from COVID but from this weekend immune system having to fight off old latent viruses it once had not problem with?
- canoebuilder 4y ago
  I donno. Seems like white blood cells are kinda important. Relevant: https://nitter.ca/AlexBerenson/status/1568951911084072960#m https://nitter.ca/AlexBerenson/status/1568951911084072960#m
usrusr 4y ago
Had those mice been immunized against influenza? That's not what I read, but I might have miss it. What I read is that they used the vector without any payload, and it turned out that influenza is an example of something nominally unrelated where resistance was slightly increased while candida albicans (no idea what that is, not a native speaker) are an example for slightly lessened resistance. Lines up well with my mental model of how the immune system deals with the unknown: a million monkeys not on typewriters but on text editors with copy/paste. Who fire new code, aimlessly mashed up from their library of previous experience, at a test fixture. Any change to unrelated previous experience can increase or decrease their chance of finding something that sticks.
- _benedict 4y ago
  No, they then followed up with an influenza vaccine delivered by mRNA. This study assessed the relative quality of immune response in those that had previously received a sham vaccine delivered by LNP, or no prior vaccine (or LNP). > Two weeks later, the mice were injected in the same area with 2.5 μg of mRNA-LNP coding for PR8 influenza hemagglutinin (HA)
- visarga 4y ago
  Apparently our T-cells learn from unlicensed data just like our AIs.
xienze 4y ago
> Also: this is purely in mice. They have zero data on whether this is true for humans. Out of curiosity, how do you feel about the new bivalent BA4/BA5 booster? It's only been tested on... eight mice [0]: > So what data specific to the BA.4/BA.5 boosters, did the FDA use to expand the EUAs to include the BA.4/BA.5 boosters? Well, the answer is at least in part very “mice.” Apparently, both Moderna and Pfizer-BioNTech have provided non-human animal data on the BA.4/BA.5 boosters to the FDA to state their case for the EUA. But they haven’t yet shown this data to the rest of the scientific community or the public. This data have reportedly included some preliminary findings from eight mice. Hey, if that's good enough for emergency use authorization, why aren't the findings in this paper up to snuff? 0: https://www.forbes.com/sites/brucelee/2022/09/12/have-the-new-bivalent-covid-19-vaccine-boosters-been-tested-on-humans/?sh=2b249b573838 https://www.forbes.com/sites/brucelee/2022/09/12/have-the-ne...
- ceejayoz 4y ago
  A reminder that anyone can be a "Forbes contributor" (https://www.niemanlab.org/2022/02/an-incomplete-history-of-forbes-com-as-a-platform-for-scams-grift-and-bad-journalism/ https://www.niemanlab.org/2022/02/an-incomplete-history-of-f...), and "reportedly" is thrown in there with zero evidence. It's highly unlikely the booster trials were on eight mice. edit: Found the source of the eight mouse thing; it's a misreading of https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2022-09-01/06-COVID-Miller-508.pdf https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-..., page 21. It's not the safety trial, it's the immunogenicity comparison on a small population of older mice previously given the primary vaccine. (The previous slide, #20, has a heading of "Pre-Clinical Studies"; #21 is describing the early studies before the human trials.) Page six debunks the idea it's only been tested on mice entirely; it cites a trial of 512 human adults for the Moderna BA.4/BA.5 Omicron booster.
  - orange_fritter 4y ago
    Page six labels the 512 BA.4/BA.5 test as "Part H" > Part H enrolled Aug 10-23, 2022 These people entered the study less than a month ago? https://www.npr.org/sections/health-shots/2022/08/18/1117778748/whats-behind-the-fdas-controversial-strategy-for-evaluating-new-covid-boosters https://www.npr.org/sections/health-shots/2022/08/18/1117778...
airstrike 4y ago
More importantly, it’s unclear whether this tradeoff also happens with exposure to the actual virus
easytiger 4y ago
> It sounds to me as though the tradeoff being made here is: a slightly decreased immune response generally, but a better immune response to the thing you've been immunized against. No compromise was posited, it is a consequence not a trade off. Not remotely the same
candiddevmike 4y ago
Someone made a good log scale representation on how effective the vaccines are: https://www.reddit.com/r/dataisbeautiful/comments/pjmeqh/oc_side_effect_risks_from_getting_an_mrna_vaccine/ https://www.reddit.com/r/dataisbeautiful/comments/pjmeqh/oc_...
mark_l_watson 4y ago
I agree with you. Also, a problem with the vaccinations is inflammation. A well planned and implemented diet can reduce inflammation. Indeed, my wife and I always tune up our diets to decrease inflammatory foods while eating as many anti-inflammatory foods as possible, and we have been doing this since long before Covid-19.
nikolay 4y ago
Not a good tradeoff for RNA viruses that mutate so widely.

by mabbo 4y ago

sawyna 4y ago

Well, the paper quotes unexpected changes in your adaptive immune response. What's observed is a slight decrease of immune response in mice for a highly specific condition. We don't know how the overall immune response changes. For all you know, small decreases in immune response to diseases might bubble up to be a significant decrease.

lazyier 4y ago

I donno. Seems like white blood cells are kinda important. We have a huge number of interactions with bacteria and viruses and all sorts of microorganisms. Hundreds? Thousands times a day? Scratches in the kitchen while preparing food, for example, floods our body with stuff that white blood cells are required to deal with. Giving up some of the ability to deal with those for a small reduction in the symptoms associated with a specific disease doesn't seem like a useful trade off.

dangerlibrary 4y ago
Over a million people, in the U.S. alone, died in under two years after being infected with this virus. Even granting the unlikely possibility that this mouse model is reflective of the immune response in humans, whatever other microorganisms people were encountering were demonstrably less dangerous than SARS-CoV-2. Unless you know of some other highly infectious microorganism that rapidly spread to hundreds of millions of people and killed 1-2% of those it infected?
- taolegal 4y ago
  > Even granting the genuinely unlikely possibility that this mouse model is reflective of the immune response in humans, whatever other microorganisms people were encountering were demonstrably less dangerous than SARS-CoV-2. The mouse model is apparently enough for the new booster.
  - peter422 4y ago
    So they ran the phase 2/3 trial in >1000 humans for fun? The problem with anti-vaxxers is you just imagine a world in which everything is underhanded and a conspiracy when all the science and data is out there in the open, just ignored.
    - taolegal 4y ago
      Anti-vax? You have no clue what my beliefs are on this, I'm not anti-vaccine. I remember just last year the Biden administration forced through the booster shots (after a propaganda campaign predicated one & done, that then extended into mandates, which Biden, Pelosi & others said were never on the table or illegal, later to be proven unconstitutional by the supreme court). Senior officials at the FDA resigned over the insufficient evidence of efficacy. Not only was it unclear that they should be approved for seniors, they just opened it up to everyone. It's only gotten worse now. It's not even remotely clear to me that the average healthy person (not on the standard American diet, chronically ill with the typical stuff like diabetes & obesity) needs upwards of 4 vaccines, and counting, for a virus that's much more attenuated & practically everyone has some form of immunity at this point. Also: to answer your question, from what I can tell the studies haven't shown efficacy. They only show that antibodies rose, which we know isn't absolute proof of efficacy with regards to infection or disease.
      - peter422 4y ago
        I never said the trials showed efficacy, though there are multiple high quality trials which do show serious benefits of 3rd/4th shots in various age groups. I just say they ran human trials, which your comment implied they didn’t. Also: - no good evidence the virus is attenuated (lower hospitalizations/mortality likely driven by increased population immunity) - a lot of FDA/CDC officials agreed with the decision too, and I think on the whole were proved right to offer to the booster to older populations before all the studies were completed. - nobody is forcing you to get the 3rd/4th shots, why do you want to prevent other people from getting them if they want them? You are sooo sure they are bad?
deleted 4y ago
[deleted]
mabbo 4y ago
But the thing is we ran a massive experiment on this called "The covid-19 pandemic". What we saw was no serious increase in mortality for the immunized, and a significant increase in mortality for the non-immunized. Seems like the data from that experiment should be taken into consideration when deciding if the tradeoff is worthwhile, right?
- origin_path 4y ago
  Two problems: 1. That wasn't a controlled experiment. Observational data < RCTs. 2. You are mixing up mortality and mortality attributed to COVID. It's a common error. For overall mortality the picture is far less clear. For example in the Pfizer trials there were more deaths overall in the vaccinated arm than the unvaccinated arm i.e. RCT evidence = no mortality benefit. Also, we now have excess deaths above the expected baseline for long periods in 2022, which is unprecedented. Governments are highly reluctant to split these deaths out by vaccine status, but the increase seems mostly attributed to heart and blood clotting related deaths. So the data from the "experiment" is not obviously positive.
  - ttpphd 4y ago
    [flagged]
    - logic_beats_pro 4y ago
      As you see in the article, this is a mathematical model which indicates vaccines saved 20,000,000 lives. It is completely unprovable and only serves as a nice sounding talking point. I also could claim 20,000,000 lives were saved by natural immunity. Or vitamin D from sunshine. Or the placebo effect. All of those mentioned are also not provable.
      - blackbear_ 4y ago
        Do you have specific reasons not to believe the model and/or data in that article, beyond "all models are wrong by definition"?
dragontamer 4y ago
You're welcome to post the other pandemics that occurred in 2020 through 2022. Flu was practically wiped out for example. COVID19 was more fit, and many people were taking precautions (ie: masks) that also hampered the spread of Flu. If mRNA vaccines really inhibited general immune response to other viruses / bacteria, it should be demonstrable. Just line up the number of people who died / got sick of non-COVID19 diseases in 2020 through 2022 and compare them to the COVID19 vaccine patients, stratified for age/sex/race.
- zionic 4y ago
  >Just line up the number of people who died / got sick of non-COVID19 diseases in 2020 This is _extremely_ difficult to do, as a mix of both incentive structures and poor policy lead to any death with a positive PCR test being counted as a COVID death. It's practically impossible now to go back and figure out how many were _actually_ "killed by COVID" vs "died _with_ COVID".
  - peter422 4y ago
    Most people who had covid and died probably wouldn’t have died so quickly if they didn’t have covid. Why you do the mental gymnastics to pretend this isn’t true is so baffling.
    - spookthesunset 4y ago
      I’m sure George Floyd would have lived a little longer if he wasn’t Covid positive when he died. It doesn’t matter anyway. The data required to support our mitigations stopped mattering a long long time ago. ..Sometime back when the “4% kill rate” predicted by the imperial college paper turned out to be very very wrong and when all those temporary military hospital things got closed because they weren’t being used. That might have been a good time to reevaluate what the fuck we were doing but instead of celebrating the fact that Covid wasn’t nearly as bad as predicted we just doubled down for a year and a half more instead. Honestly it’s best to just take the numbers at face value and assume any overcount is balanced by undercounts.
manwe150 4y ago
As another commented pointed out, we have hundreds of millions of data points in people now post-vaccination and post-boosters, which haven’t detected a problem, and only 12 here in mice, that the authors suggest warrants further study. Which hypothesis are you saying has “no data”?
- junofan 4y ago
  It took only 12 mice to find unexpected effects? How was the vaccine tested again?
  - Sohcahtoa82 4y ago
    > It took only 12 That's a very small sample size. Also, it's mice.
  - yojo 4y ago
    You’d be amazed at the number of unexpected effects I could find studying just a single mouse! Having a small number data points means that a single outlier can impact your results. And since “no results” typically doesn’t get published, the rare events end up disproportionately represented in journals. The smaller the sample size, the more likely the “effect” you’re seeing is just random chance.
- FollowingTheDao 4y ago
  It is hard to see a problem if you are not looking for it or if the cause is distant from the reaction. An Example: My friend had undiagnosed alpha gal for months because the anaphylactic reaction happened to him more than 12 hours after eating red meat so they did not know the connection. Is Long Covid actually not from COVID but from this weekend immune system having to fight off old latent viruses it once had not problem with?
canoebuilder 4y ago
I donno. Seems like white blood cells are kinda important. Relevant: https://nitter.ca/AlexBerenson/status/1568951911084072960#m https://nitter.ca/AlexBerenson/status/1568951911084072960#m

usrusr 4y ago

Had those mice been immunized against influenza? That's not what I read, but I might have miss it. What I read is that they used the vector without any payload, and it turned out that influenza is an example of something nominally unrelated where resistance was slightly increased while candida albicans (no idea what that is, not a native speaker) are an example for slightly lessened resistance. Lines up well with my mental model of how the immune system deals with the unknown: a million monkeys not on typewriters but on text editors with copy/paste. Who fire new code, aimlessly mashed up from their library of previous experience, at a test fixture. Any change to unrelated previous experience can increase or decrease their chance of finding something that sticks.

_benedict 4y ago
No, they then followed up with an influenza vaccine delivered by mRNA. This study assessed the relative quality of immune response in those that had previously received a sham vaccine delivered by LNP, or no prior vaccine (or LNP). > Two weeks later, the mice were injected in the same area with 2.5 μg of mRNA-LNP coding for PR8 influenza hemagglutinin (HA)
visarga 4y ago
Apparently our T-cells learn from unlicensed data just like our AIs.

xienze 4y ago

> Also: this is purely in mice. They have zero data on whether this is true for humans. Out of curiosity, how do you feel about the new bivalent BA4/BA5 booster? It's only been tested on... eight mice [0]: > So what data specific to the BA.4/BA.5 boosters, did the FDA use to expand the EUAs to include the BA.4/BA.5 boosters? Well, the answer is at least in part very “mice.” Apparently, both Moderna and Pfizer-BioNTech have provided non-human animal data on the BA.4/BA.5 boosters to the FDA to state their case for the EUA. But they haven’t yet shown this data to the rest of the scientific community or the public. This data have reportedly included some preliminary findings from eight mice. Hey, if that's good enough for emergency use authorization, why aren't the findings in this paper up to snuff? 0: https://www.forbes.com/sites/brucelee/2022/09/12/have-the-new-bivalent-covid-19-vaccine-boosters-been-tested-on-humans/?sh=2b249b573838 https://www.forbes.com/sites/brucelee/2022/09/12/have-the-ne...

ceejayoz 4y ago
A reminder that anyone can be a "Forbes contributor" (https://www.niemanlab.org/2022/02/an-incomplete-history-of-forbes-com-as-a-platform-for-scams-grift-and-bad-journalism/ https://www.niemanlab.org/2022/02/an-incomplete-history-of-f...), and "reportedly" is thrown in there with zero evidence. It's highly unlikely the booster trials were on eight mice. edit: Found the source of the eight mouse thing; it's a misreading of https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2022-09-01/06-COVID-Miller-508.pdf https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-..., page 21. It's not the safety trial, it's the immunogenicity comparison on a small population of older mice previously given the primary vaccine. (The previous slide, #20, has a heading of "Pre-Clinical Studies"; #21 is describing the early studies before the human trials.) Page six debunks the idea it's only been tested on mice entirely; it cites a trial of 512 human adults for the Moderna BA.4/BA.5 Omicron booster.
- orange_fritter 4y ago
  Page six labels the 512 BA.4/BA.5 test as "Part H" > Part H enrolled Aug 10-23, 2022 These people entered the study less than a month ago? https://www.npr.org/sections/health-shots/2022/08/18/1117778748/whats-behind-the-fdas-controversial-strategy-for-evaluating-new-covid-boosters https://www.npr.org/sections/health-shots/2022/08/18/1117778...

airstrike 4y ago

More importantly, it’s unclear whether this tradeoff also happens with exposure to the actual virus

easytiger 4y ago

> It sounds to me as though the tradeoff being made here is: a slightly decreased immune response generally, but a better immune response to the thing you've been immunized against. No compromise was posited, it is a consequence not a trade off. Not remotely the same

candiddevmike 4y ago

Someone made a good log scale representation on how effective the vaccines are: https://www.reddit.com/r/dataisbeautiful/comments/pjmeqh/oc_side_effect_risks_from_getting_an_mrna_vaccine/ https://www.reddit.com/r/dataisbeautiful/comments/pjmeqh/oc_...

mark_l_watson 4y ago

I agree with you. Also, a problem with the vaccinations is inflammation. A well planned and implemented diet can reduce inflammation. Indeed, my wife and I always tune up our diets to decrease inflammatory foods while eating as many anti-inflammatory foods as possible, and we have been doing this since long before Covid-19.

nikolay 4y ago

Not a good tradeoff for RNA viruses that mutate so widely.