4 ms·

Infection-enhancing antibodies have been detected in symptomatic Covid-19 among the vaccinated. It's no longer theoretical that antibody dependent enhancement

Infection-enhancing antibodies have been detected in symptomatic Covid-19 among the vaccinated. It's no longer theoretical that antibody dependent enhancement (ADE) is a concern for the vaccinated. The enhancing antibodies recognize both the Wuhan strain and Delta variants. ADE of Delta variants is a potential risk for current vaccines. Vaccine formulations lacking ADE epitope are suggested, but the majority of people are already vaccinated with problematic formulations.

PaulHoule 5y ago
Is it really a problem, at least with the Delta variant? It seems quite a few vaccinated people get COVID-19 but it seems very few get seriously ill. The protective effect seems to outweigh any infection-enhancing effect.
- willmadden 5y ago
  >It seems quite a few vaccinated people get COVID-19 but it seems very few get seriously ill. You need to skate where the puck is going. If you look at the data coming out of Israel, which is ahead of everyone else on the curve with vaccinations (and also releases data without manipulating it first, unlike the US - which uses exponentially looser rules for diagnosing COVID in the unvaccinated versus the vaccinated), you get a very different story. https://www.visiontimes.com/2021/08/08/israel-hospital-vaccinated.html https://www.visiontimes.com/2021/08/08/israel-hospital-vacci... Wait two months and the US and other countries will be where Israel is today. The risk with ADE increases as antibody levels from the vaccinations wane. That's happening now.
  - jimmyswimmy 5y ago
    Not thrilled with that source. But given that Israel has such a high rate of vaccination, it seems reasonable to expect that most of those admitted to hospital at this point will have had the vaccine.
    - willmadden 5y ago
      According to the source, the rate of hospitalizations and critical cases is higher amongst the vaccinated, even adjusting for the higher overall vaccination rates. You could make the claim that it isn't age adjusted, but it's hard to make that case when almost all (90%+) of the people being hospitalized are vaccinated, when the general population is ~70% vaccinated. I agree the source isn't great, but it's hard finding information that hasn't been spun by tech companies at this point. It's worth watching the data coming out of Israel.
  - wlesieutre 5y ago
    > She said, “This battle is not between the right and the left, it’s not between conservatives and liberals or Republicans and Democrats.” Rather, “this is a battle between Our Lord and the devil,” and every person must choose a side. ... > She said, “If we treat them early – early is the ticket – with ivermectin and hydroxychloroquine, 80% of the people will not have to go to the hospital.” I was under the impression that neither invermectin or hydroxychloroquine has been demonstrated to be effective. https://www.medrxiv.org/content/10.1101/2021.02.18.21252037v1 https://www.medrxiv.org/content/10.1101/2021.02.18.21252037v... However you feel about vaccines being foisted on us by the devil, that article looks pretty shaky to me as a source of public health advice.
    - dave_sullivan 5y ago
      > Requiring COVID-19 jabs has become a way to exercise “total control” over people. “They want to force an experimental compound that we really don’t know the long-term effects [of]. Then they want to, on top of that, make sure everyone has a [vaccine] passport. So, it’s total control of a populace. And that’s communism. We’re headed that way,” she said. This gave me a chuckle and did not inspire confidence.
      - willmadden 5y ago
        France is on the brink of a revolution over vaccine passports. Police are inspecting peoples' "papers" at restaurants, and there are anti-passport protests with police leading the parade. There are full blown brownshirt squads in Australia. Police are beating protesters in Canada. It's not only reasonable to hypothesize this is about control, to me it's irrational to think otherwise at this point.
    - willmadden 5y ago
      Ivermectin is incredibly effective. It's just not profitable. Here is a meta analysis of 63 (so far) randomized double blind trials: https://ivmmeta.com/ https://ivmmeta.com/
      - lucd 5y ago
  - sorethescore 5y ago
    So far we haven't seen any evidence of ADE in-vivo. Until that data shows up we shouldn't be jumping to any conclusions based on in-vitro or other computational models.
    - willmadden 5y ago
      I disagree that we should wait until we see ADE in the general public before addressing it as a risk. If ADE hits the vaccinated population and is as serious as it was with other viruses, like SARS-1, it will be a catastrophe of biblical proportions.
  - dtwest 5y ago
    Could you elaborate on how the US data is manipulated or why it is lower quality than Israel's?
    - willmadden 5y ago
      I would be happy to. The CDC changed their guidance with PCR testing so a "breakthrough case" (i.e. a vaccinated person testing positive for COVID) is defined as 28 cycles or fewer, but gave no guidance about changing the PCR cycle count for unvaccinated (which remains in the 35-40 range most places). This means it takes thousands of times less material to make an unvaccinated person a COVID "case" than a vaccinated person. https://www.cdc.gov/vaccines/covid-19/health-departments/breakthrough-cases.html https://www.cdc.gov/vaccines/covid-19/health-departments/bre... They constantly stealth-edit the page, so it's helpful to look at archived versions here: https://archive.is/https://www.cdc.gov/vaccines/covid-19/health-departments/breakthrough-cases.html https://archive.is/https://www.cdc.gov/vaccines/covid-19/hea... Here's an article about it: https://washingtonwatch.org/caught-red-handed-cdc-changes-test-thresholds-to-virtually-eliminate-new-covid-cases/ https://washingtonwatch.org/caught-red-handed-cdc-changes-te...
criticaltinker 5y ago
> It's no longer theoretical that antibody dependent enhancement (ADE) is a concern for the vaccinated IMO this is too strongly worded and doesn't paint an accurate picture. First of all, ADE is a concern for anyone infected by a virus, whether through vaccination or natural infection. Second, there is substantial literature showing that immune responses can still be protective even in the presence of ADE [1]. Third, OP uses a molecular modelling approach which places it mostly in the realm of theory and far from conclusive clinical evidence. Some quotes from [1] to support my point: > It is clear that after many years, and considerable attention, the understanding of ADE of disease after either vaccination or administration of antiviral antibodies is insufficient to confidently predict that a given immune intervention for a viral infection will have negative outcomes in humans. > Despite the importance that such information would have in the COVID-19 pandemic, in vitro assays do not predict ADE of disease. > Most animal models of vaccines and antibody interventions show protection, whereas those that suggest potential ADE of disease are not definitive and the precise mechanisms have not been defined. > Although ADE is a concern, it is also clear that antibodies are a fundamentally important component of protective immunity to all of the pathogens discussed here > Even when vaccine formulations such as formalin inactivation have shown disease enhancement, neutralizing antibodies with optimized properties have been protective. [1] A perspective on potential antibody-dependent enhancement of SARS-CoV-2 https://www.nature.com/articles/s41586-020-2538-8 https://www.nature.com/articles/s41586-020-2538-8
- raphlinus 5y ago
  More background, well written and accessible to a wider audience: https://blogs.sciencemag.org/pipeline/archives/2021/02/12/antibody-dependent-enhancement-and-the-coronavirus-vaccines https://blogs.sciencemag.org/pipeline/archives/2021/02/12/an... An interesting fact: concern about ADE is a significant reason all the vaccines target the spike protein rather than any of the others, such as N (nucleoprotein).
  - willmadden 5y ago
    That article is from February 2021. If the author updated the article to include the paper I linked, he could no longer make this claim: "...and (so far) no sign of ADE even with the variant strains in different parts of the world. We have things to worry about in this pandemic, but as far as I can tell today, antibody-dependent enhancement does not seem to be one of them. I understand why people would worry about it, and want to avoid it. But if you’re coming across reports that say that it’s a real problem right now and that you should avoid getting vaccinated because of it, well, I just don’t see it. Some of that is well-intentioned caution, and some of it is probably flat-out anti-vaccine scaremongering. Anyone with different data or different impressions, well, that’s why the comments are open around here!" I'ld be curious to see how the author would update the article based on what we see from the molecular modeling in the paper that broke this week.

PaulHoule 5y ago

Is it really a problem, at least with the Delta variant? It seems quite a few vaccinated people get COVID-19 but it seems very few get seriously ill. The protective effect seems to outweigh any infection-enhancing effect.

willmadden 5y ago
>It seems quite a few vaccinated people get COVID-19 but it seems very few get seriously ill. You need to skate where the puck is going. If you look at the data coming out of Israel, which is ahead of everyone else on the curve with vaccinations (and also releases data without manipulating it first, unlike the US - which uses exponentially looser rules for diagnosing COVID in the unvaccinated versus the vaccinated), you get a very different story. https://www.visiontimes.com/2021/08/08/israel-hospital-vaccinated.html https://www.visiontimes.com/2021/08/08/israel-hospital-vacci... Wait two months and the US and other countries will be where Israel is today. The risk with ADE increases as antibody levels from the vaccinations wane. That's happening now.
- jimmyswimmy 5y ago
  Not thrilled with that source. But given that Israel has such a high rate of vaccination, it seems reasonable to expect that most of those admitted to hospital at this point will have had the vaccine.
  - willmadden 5y ago
    According to the source, the rate of hospitalizations and critical cases is higher amongst the vaccinated, even adjusting for the higher overall vaccination rates. You could make the claim that it isn't age adjusted, but it's hard to make that case when almost all (90%+) of the people being hospitalized are vaccinated, when the general population is ~70% vaccinated. I agree the source isn't great, but it's hard finding information that hasn't been spun by tech companies at this point. It's worth watching the data coming out of Israel.
- wlesieutre 5y ago
  > She said, “This battle is not between the right and the left, it’s not between conservatives and liberals or Republicans and Democrats.” Rather, “this is a battle between Our Lord and the devil,” and every person must choose a side. ... > She said, “If we treat them early – early is the ticket – with ivermectin and hydroxychloroquine, 80% of the people will not have to go to the hospital.” I was under the impression that neither invermectin or hydroxychloroquine has been demonstrated to be effective. https://www.medrxiv.org/content/10.1101/2021.02.18.21252037v1 https://www.medrxiv.org/content/10.1101/2021.02.18.21252037v... However you feel about vaccines being foisted on us by the devil, that article looks pretty shaky to me as a source of public health advice.
  - dave_sullivan 5y ago
    > Requiring COVID-19 jabs has become a way to exercise “total control” over people. “They want to force an experimental compound that we really don’t know the long-term effects [of]. Then they want to, on top of that, make sure everyone has a [vaccine] passport. So, it’s total control of a populace. And that’s communism. We’re headed that way,” she said. This gave me a chuckle and did not inspire confidence.
    - willmadden 5y ago
      France is on the brink of a revolution over vaccine passports. Police are inspecting peoples' "papers" at restaurants, and there are anti-passport protests with police leading the parade. There are full blown brownshirt squads in Australia. Police are beating protesters in Canada. It's not only reasonable to hypothesize this is about control, to me it's irrational to think otherwise at this point.
  - willmadden 5y ago
    Ivermectin is incredibly effective. It's just not profitable. Here is a meta analysis of 63 (so far) randomized double blind trials: https://ivmmeta.com/ https://ivmmeta.com/
    - lucd 5y ago
- sorethescore 5y ago
  So far we haven't seen any evidence of ADE in-vivo. Until that data shows up we shouldn't be jumping to any conclusions based on in-vitro or other computational models.
  - willmadden 5y ago
    I disagree that we should wait until we see ADE in the general public before addressing it as a risk. If ADE hits the vaccinated population and is as serious as it was with other viruses, like SARS-1, it will be a catastrophe of biblical proportions.
- dtwest 5y ago
  Could you elaborate on how the US data is manipulated or why it is lower quality than Israel's?
  - willmadden 5y ago
    I would be happy to. The CDC changed their guidance with PCR testing so a "breakthrough case" (i.e. a vaccinated person testing positive for COVID) is defined as 28 cycles or fewer, but gave no guidance about changing the PCR cycle count for unvaccinated (which remains in the 35-40 range most places). This means it takes thousands of times less material to make an unvaccinated person a COVID "case" than a vaccinated person. https://www.cdc.gov/vaccines/covid-19/health-departments/breakthrough-cases.html https://www.cdc.gov/vaccines/covid-19/health-departments/bre... They constantly stealth-edit the page, so it's helpful to look at archived versions here: https://archive.is/https://www.cdc.gov/vaccines/covid-19/health-departments/breakthrough-cases.html https://archive.is/https://www.cdc.gov/vaccines/covid-19/hea... Here's an article about it: https://washingtonwatch.org/caught-red-handed-cdc-changes-test-thresholds-to-virtually-eliminate-new-covid-cases/ https://washingtonwatch.org/caught-red-handed-cdc-changes-te...

criticaltinker 5y ago

> It's no longer theoretical that antibody dependent enhancement (ADE) is a concern for the vaccinated IMO this is too strongly worded and doesn't paint an accurate picture. First of all, ADE is a concern for anyone infected by a virus, whether through vaccination or natural infection. Second, there is substantial literature showing that immune responses can still be protective even in the presence of ADE [1]. Third, OP uses a molecular modelling approach which places it mostly in the realm of theory and far from conclusive clinical evidence. Some quotes from [1] to support my point: > It is clear that after many years, and considerable attention, the understanding of ADE of disease after either vaccination or administration of antiviral antibodies is insufficient to confidently predict that a given immune intervention for a viral infection will have negative outcomes in humans. > Despite the importance that such information would have in the COVID-19 pandemic, in vitro assays do not predict ADE of disease. > Most animal models of vaccines and antibody interventions show protection, whereas those that suggest potential ADE of disease are not definitive and the precise mechanisms have not been defined. > Although ADE is a concern, it is also clear that antibodies are a fundamentally important component of protective immunity to all of the pathogens discussed here > Even when vaccine formulations such as formalin inactivation have shown disease enhancement, neutralizing antibodies with optimized properties have been protective. [1] A perspective on potential antibody-dependent enhancement of SARS-CoV-2 https://www.nature.com/articles/s41586-020-2538-8 https://www.nature.com/articles/s41586-020-2538-8

raphlinus 5y ago
More background, well written and accessible to a wider audience: https://blogs.sciencemag.org/pipeline/archives/2021/02/12/antibody-dependent-enhancement-and-the-coronavirus-vaccines https://blogs.sciencemag.org/pipeline/archives/2021/02/12/an... An interesting fact: concern about ADE is a significant reason all the vaccines target the spike protein rather than any of the others, such as N (nucleoprotein).
- willmadden 5y ago
  That article is from February 2021. If the author updated the article to include the paper I linked, he could no longer make this claim: "...and (so far) no sign of ADE even with the variant strains in different parts of the world. We have things to worry about in this pandemic, but as far as I can tell today, antibody-dependent enhancement does not seem to be one of them. I understand why people would worry about it, and want to avoid it. But if you’re coming across reports that say that it’s a real problem right now and that you should avoid getting vaccinated because of it, well, I just don’t see it. Some of that is well-intentioned caution, and some of it is probably flat-out anti-vaccine scaremongering. Anyone with different data or different impressions, well, that’s why the comments are open around here!" I'ld be curious to see how the author would update the article based on what we see from the molecular modeling in the paper that broke this week.