6 ms·

Note this is to inform public health / prioritization in the short term. (Which is less necessary places like the US where there is excess vaccine supply). We

by mlyle 5y ago

Note this is to inform public health / prioritization in the short term. (Which is less necessary places like the US where there is excess vaccine supply). We know that past infection greatly reduces risk (and this helps quantify it). At the same time, vaccination is thought to cause a much broader and more durable immune response than natural infection. We'd like people who were previously infected to get vaccinated eventually for these benefits, but they're not who you'd want to vaccinate first.

tomp 5y ago
> vaccination is thought to cause a much broader and more durable immune response than natural infection Why? Is there any data to support this assertion? If anything, being ill (symptomatic) means the viral load was high in the body, so the immune system response should be as well, and in addition, infection should cause the immune system to produce antibodies to all parts of the virus, not just the spike protein, as with mRNA vaccines.
- jjgreen 5y ago
  "it is thought" I guess comes from nonsense like this: https://www.huffingtonpost.co.uk/entry/does-the-vaccine-give-better-protection-than-having-fought-off-the-virus_uk_601c0663c5b62bf30754c563 https://www.huffingtonpost.co.uk/entry/does-the-vaccine-give...
  - mlyle 5y ago
    It comes from nonsense like this: https://www.nejm.org/doi/full/10.1056/NEJMc2032195 https://www.nejm.org/doi/full/10.1056/NEJMc2032195
- akomtu 5y ago
  If there was evidence, that "is thought to" would've been replaced with "is proven to".
  - mlyle 5y ago
    https://www.nejm.org/doi/full/10.1056/NEJMc2032195 https://www.nejm.org/doi/full/10.1056/NEJMc2032195 Shows a slow decay in neutralizing antibody titers in those vaccinated, with a greater degree of viral inhibition months later than convalescent plasma at a month. "At day 119, the binding and neutralizing GMTs exceeded the median GMTs in a panel of 41 controls who were convalescing from Covid-19, with a median of 34 days since diagnosis (range, 23 to 54)." There's also data showing much higher neutralization titers against variants in those vaccinated vs. those naturally infected. Of course, this is only one measure of immune response. Many other things are more difficult to measure, so we don't know too much about e.g. T cell responses from natural infection vs. vaccination. So it's hardly proven but there is some highly suggestive evidence.
- mlyle 5y ago
  Yes! https://www.nejm.org/doi/full/10.1056/NEJMc2032195 https://www.nejm.org/doi/full/10.1056/NEJMc2032195 Shows a slow decay in neutralizing antibody titers, with a greater degree of viral inhibition months later than convalescent plasma at a month. "At day 119, the binding and neutralizing GMTs exceeded the median GMTs in a panel of 41 controls who were convalescing from Covid-19, with a median of 34 days since diagnosis (range, 23 to 54)." Note that antibodies to all parts of the virus aren't necessarily equally beneficial, because only a few functional areas are neutralizing.
  - rolph 5y ago
    neutralizing antibodies will give protection against cell entry to the degree they saturate the binding kinetics between receptor and ligand. non neutralizing does not mean ineffective, as ^any^ antibody is a lable that will provoke a complement based immune response, further leading to Tcell based production of antibodies that also include Ab that will bind to domains of spike that are essential to cell entry
    - mlyle 5y ago
      Sure, non-neutralizing binding antibodies are also useful. I think you maybe meant to respond to the parent of my comment. The paper shows high binding affinities and high neutralization titers in comparison to convalescent plasma.
- mlyle 5y ago
  Just a little more data-- For a long time (from the phase 2 trials of the vaccines) we knew that they generated a very large immune response compared to natural infection: https://www.nejm.org/na101/home/literatum/publisher/mms/journals/content/nejm/2020/nejm_2020.383.issue-20/nejmoa2022483/20201106/images/img_xlarge/nejmoa2022483_f2.jpeg https://www.nejm.org/na101/home/literatum/publisher/mms/jour... And recent research shows vaccination far outperforming past history of natural infection wrt: variants--https://www.nature.com/articles/s41586-021-03324-6/figures/1 https://www.nature.com/articles/s41586-021-03324-6/figures/1
mikedilger 5y ago
Not that I have any knowledge on this subject, but why would a vaccine that stimulates the creation of a bit of spike protein create a "much broader and more durable immune response" than the actual virus which I presume creates a hell of a lot more of that exact same spike protein? Genuinely curious, because my simpleton assumption would be the opposite.
- sdflhasjd 5y ago
  Also no knowledge on the subject, but I can image a case where it is more durable: If the spike protein is absolutely critical to the virus, but can't change too much without affecting function, an immune response that is specifically targetted against it would be better than an immune response against any other protein that could change without affecting the function.
- microtherion 5y ago
  My mental model of this (and I'm not a medical expert) is that (a) for a given amount of spike protein, the immune response is similar, whether the protein originates from the vaccine or the actual virus, but (b) since the vaccine is lacking the actual health threatening properties of the virus, you can expose people to massive doses of it without incurring much risk.
  - roody15 5y ago
    My place employment had almost 280 people get vaccinated (myself included). On the second dose well over 50 percent came down with flu like symptoms about 12 hours later. I was sick for 3 days and my wife was sick for 2. Would be curious on this forum on how many people got sick from Moderna.
    - mlyle 5y ago
      30 percent+ have significant side effects on the second dose. This is more significant in people in their early 20's. My wife and I are in our 40s. I had a really sore arm (like, the whole arm, not the injection site) and we were both tired for a day afterwards.

by mlyle 5y ago

tomp 5y ago

> vaccination is thought to cause a much broader and more durable immune response than natural infection Why? Is there any data to support this assertion? If anything, being ill (symptomatic) means the viral load was high in the body, so the immune system response should be as well, and in addition, infection should cause the immune system to produce antibodies to all parts of the virus, not just the spike protein, as with mRNA vaccines.

jjgreen 5y ago
"it is thought" I guess comes from nonsense like this: https://www.huffingtonpost.co.uk/entry/does-the-vaccine-give-better-protection-than-having-fought-off-the-virus_uk_601c0663c5b62bf30754c563 https://www.huffingtonpost.co.uk/entry/does-the-vaccine-give...
- mlyle 5y ago
  It comes from nonsense like this: https://www.nejm.org/doi/full/10.1056/NEJMc2032195 https://www.nejm.org/doi/full/10.1056/NEJMc2032195
akomtu 5y ago
If there was evidence, that "is thought to" would've been replaced with "is proven to".
- mlyle 5y ago
  https://www.nejm.org/doi/full/10.1056/NEJMc2032195 https://www.nejm.org/doi/full/10.1056/NEJMc2032195 Shows a slow decay in neutralizing antibody titers in those vaccinated, with a greater degree of viral inhibition months later than convalescent plasma at a month. "At day 119, the binding and neutralizing GMTs exceeded the median GMTs in a panel of 41 controls who were convalescing from Covid-19, with a median of 34 days since diagnosis (range, 23 to 54)." There's also data showing much higher neutralization titers against variants in those vaccinated vs. those naturally infected. Of course, this is only one measure of immune response. Many other things are more difficult to measure, so we don't know too much about e.g. T cell responses from natural infection vs. vaccination. So it's hardly proven but there is some highly suggestive evidence.
mlyle 5y ago
Yes! https://www.nejm.org/doi/full/10.1056/NEJMc2032195 https://www.nejm.org/doi/full/10.1056/NEJMc2032195 Shows a slow decay in neutralizing antibody titers, with a greater degree of viral inhibition months later than convalescent plasma at a month. "At day 119, the binding and neutralizing GMTs exceeded the median GMTs in a panel of 41 controls who were convalescing from Covid-19, with a median of 34 days since diagnosis (range, 23 to 54)." Note that antibodies to all parts of the virus aren't necessarily equally beneficial, because only a few functional areas are neutralizing.
- rolph 5y ago
  neutralizing antibodies will give protection against cell entry to the degree they saturate the binding kinetics between receptor and ligand. non neutralizing does not mean ineffective, as ^any^ antibody is a lable that will provoke a complement based immune response, further leading to Tcell based production of antibodies that also include Ab that will bind to domains of spike that are essential to cell entry
  - mlyle 5y ago
    Sure, non-neutralizing binding antibodies are also useful. I think you maybe meant to respond to the parent of my comment. The paper shows high binding affinities and high neutralization titers in comparison to convalescent plasma.
mlyle 5y ago
Just a little more data-- For a long time (from the phase 2 trials of the vaccines) we knew that they generated a very large immune response compared to natural infection: https://www.nejm.org/na101/home/literatum/publisher/mms/journals/content/nejm/2020/nejm_2020.383.issue-20/nejmoa2022483/20201106/images/img_xlarge/nejmoa2022483_f2.jpeg https://www.nejm.org/na101/home/literatum/publisher/mms/jour... And recent research shows vaccination far outperforming past history of natural infection wrt: variants--https://www.nature.com/articles/s41586-021-03324-6/figures/1 https://www.nature.com/articles/s41586-021-03324-6/figures/1

mikedilger 5y ago

Not that I have any knowledge on this subject, but why would a vaccine that stimulates the creation of a bit of spike protein create a "much broader and more durable immune response" than the actual virus which I presume creates a hell of a lot more of that exact same spike protein? Genuinely curious, because my simpleton assumption would be the opposite.

sdflhasjd 5y ago
Also no knowledge on the subject, but I can image a case where it is more durable: If the spike protein is absolutely critical to the virus, but can't change too much without affecting function, an immune response that is specifically targetted against it would be better than an immune response against any other protein that could change without affecting the function.
microtherion 5y ago
My mental model of this (and I'm not a medical expert) is that (a) for a given amount of spike protein, the immune response is similar, whether the protein originates from the vaccine or the actual virus, but (b) since the vaccine is lacking the actual health threatening properties of the virus, you can expose people to massive doses of it without incurring much risk.
- roody15 5y ago
  My place employment had almost 280 people get vaccinated (myself included). On the second dose well over 50 percent came down with flu like symptoms about 12 hours later. I was sick for 3 days and my wife was sick for 2. Would be curious on this forum on how many people got sick from Moderna.
  - mlyle 5y ago
    30 percent+ have significant side effects on the second dose. This is more significant in people in their early 20's. My wife and I are in our 40s. I had a really sore arm (like, the whole arm, not the injection site) and we were both tired for a day afterwards.