15 ms·

High genetic barrier to SARS-CoV-2 polyclonal neutralizing antibody escape

72 points by SubiculumCode 5y ago

eightysixfour 5y ago
This is interesting! > By aggregating VOC-associated and antibody-selected spike substitutions into a single polymutant spike protein, we show that 20 naturally occurring mutations in SARS-CoV-2 spike are sufficient to generate pseudotypes with near-complete resistance to the polyclonal neutralizing antibodies generated by convalescents or mRNA vaccine recipients So there are 20 known potential mutations which, when all put together, creates a virus that would be nearly completely resistant to existing vaccinations. > however, plasma from individuals who had been infected and subsequently received mRNA vaccination, neutralized pseudotypes bearing this highly resistant SARS-CoV-2 polymutant spike, or diverse sarbecovirus spike proteins. So, perhaps unsurprisingly, if you've had the virus and then received a vaccine, it appears that you have a very high level of immunity, including to future potential variants. I cannot pull the paper itself, did they test people who were breakthrough cases following vaccination (instead of infection then vaccination)?
- neurobashing 5y ago
  I think we need the denominator here to put '20' into context. 20 out of 100 million possible mutations is, meh, I'll take those odds. 20 out of 100, well, that's something else entirely, isn't it.
  - eightysixfour 5y ago
    Edited because a correction by another user helps to clarify - it is not about the 20 mutations (which they created a mutant spike will all 20 of them!) though, it is more about what was and was not effective in defendening against the mutant spike.
    - hadlock 5y ago
      Coronaviruses are RNA viruses, so there's only a single copy of the genetic material, vs DNA with two copies. The result of RNA viruses is that they typically mutate at a much higher rate than DNA viruses. There are viruses that mutate faster than Coronaviruses, though.
- twofornone 5y ago
  >So, perhaps unsurprisingly, if you've had the virus and then received a vaccine, it appears that you have a very high level of immunity Why would someone get vaccinated post infection?
  - gameswithgo 5y ago
    For more robust immunity, many people do this.
    - ngvrnd 5y ago
      it is in fact recommended.
      - scoot 5y ago
        But apparently not effective in all cases. A friend of mine in their early 20s has Covid a second time, having been vaccinated after their first infection. (To catch it once is unfortunate...)
        rednerrus 5y ago
        But these are outliers, right?
        amirhirsch 5y ago
        I don't know why your comment bothers me so much, but... No, your friend didn't have COVID a second time after being vaccinated after their first infection. Especially lacking any clarification that they were in fact tested positive both times, you are merely contributing to noise on the internet. 1) "a friend of yours" is not a data point on which others should base their worldview (unless their testicles got huge and their fiance called it off, why even share?) 2) reinfection is rare 3) it is likely the first time they think they had covid, they weren't tested, and actually had the flu. Here is the CDC information on reinfection: https://www.cdc.gov/coronavirus/2019-ncov/your-health/reinfection.html https://www.cdc.gov/coronavirus/2019-ncov/your-health/reinfe... As of August 6, 2021, the CDC has nothing conclusive to say on the matter: "Cases of reinfection with COVID-19 have been reported, but remain rare . " Anecdotes are noise, and I would encourage you to do no further research.
- zmmmmm 5y ago
  You chopped off a crucial part of the sentence that completely changes its meaning. The real sentence is: > By aggregating VOC-associated and antibody-selected spike substitutions into a single polymutant spike protein, we show that 20 naturally occurring mutations Aggregating ... into a polymutant spike. That means they put all 20 mutations together, each of them carefully selected from variants of concern or antibody attachment sites, into one single spike protein. Basically they created the most crazy supermutant resistent spike they could. The chance of which would be astronomically small in nature. And their conclusion is that even then a good dose of vaccine allows the body to eliminate it.
  - eightysixfour 5y ago
    Thanks, you're right and I've updated it to clarify. > And their conclusion is that even then a good dose of vaccine allows the body to eliminate it. That's not the same thing I got from the conclusion, it sounded like you needed to have a previous infection + the vaccine to clear it. What am I missing?
  - robrenaud 5y ago
    Did I misread? This super spike protein defeats merely the vaccinated, but not the naturally infected and then vaccinated, AFAIU.
  - openasocket 5y ago
    Additionally, could that even happen naturally? Since viruses only reproduce asexually, there's no way for multiple strain's mutations to somehow be combined together, right?
    - xbkingx 5y ago
      I think it's more of an emergent pattern. Mutant ABC is the target. First Mutant A becomes the predominant strain. There might be some Mutant AB or AC in the population, but the controlling factor is currently Mutant A. Eventually, Mutant A therapies/vaccines are introduced and Mutant A starts to lose its hold. Mutant AB isn't treated by the new treatments (or they're less effective, or Mutant AB goes undetected longer, etc.). Mutant AB becomes king of the hill. Repeat with Mutant ABC. All this would assume that there's no Mutant B or Mutant BC or Mutant AC that increases in prevalence. All the mutations would have to build up over time or occur simultaneously by coincidence (or you could get a combination). It's just basic evolution - organism follows the niche. We have a hard time recognizing it because generation turnover is so rapid. Instead of taking ~30 years for 2.5 offspring, it's a few days for millions of offspring. I don't think mode of reproduction matters much when we're talking at this scale. While the virus creates stable clones across generations, I would think they're more susceptible to mutations and any viable mutation is quickly amplified exponentially. Just like the old high school bio experiment to demonstrate antibiotic resistance, only your respiratory mucus membranes are the medium. Those bacteria reproduced asexually.
- dougmwne 5y ago
  They only tested the plasma from people who were infected, people vaccinated with Pfizer, and people who were infected, then vaccinated. The 20 mutations they mention was a set of 20 mutations to a single spike protein that they then attached to a carrier virus to test plasma neutralization. It's not the full space of possible mutations that could cause immunity escape, but it is one that they found with a plausibly low number of mutations that it could occur in the wild that would result is almost total escape for vaccinated or previously infected. An interesting result was that the infected then vaccinated individuals developed antibodies that targeted a very broad range of coronaviruses, including their engineered virus, delta, many other variants, and the original SARS. It's suggested that future vaccines could be engineered to produce this broad immunity. The immune system is almost terrifyingly complex.
  - devin 5y ago
    > An interesting result was that the infected then vaccinated individuals developed antibodies that targeted a very broad range of coronaviruses, including their engineered virus, delta, many other variants, and the original SARS. Glad you brought this up, but from what I understand this isn't actually all that interesting (read: surprising). mRNA vaccines target the spike protein because it's functional and well-conserved. Natural infection means your immune system sees many more proteins.
    - dougmwne 5y ago
      Yes, but natural infection did not produce this broad immunity in their samples, only infected then vaccinated developed this special kind of broad immunity. That is supprising in a way, that we could coax the immune system into producing a special kind of immunity that wouldn't otherwise be likely to occur naturally. It opens an area of research into what mRNA sequence or dosing regimen could reproduce this immunity for a future super vaccine.
      - angelzen 5y ago
        Natural infection was one event vs. natural infection + vaccine being two events separated by a time interval. It may be that we are stumbling upon a natural mechanism that makes recurring infections almost impossible past 2nd event.
- bpodgursky 5y ago
  Given the... possible... origins of this virus, I hope they are being exceedingly careful about actually synthesizing a virus with all of these mutations at once. Or they stand a very high risk of creating and releasing the doomsday variant they are worried about in the first place...
  - kmeisthax 5y ago
    I think they only synthesized the spike proteins, not the whole virus. You don't need a whole virus to check if a protein is neutralized or not. (For the record, if spike proteins were themselves in any way harmful to life on their own, Moderna and Pfizer wouldn't be the primary vaccine vendors for the US right now.)
    - nomel 5y ago
      > in any way harmful to life on their own I think it's fairly well accepted that they can cause myocarditis [1], which has killed some [2]. Better than getting the virus, but they appear to be capable of harm. I've naively wondered if the young men are getting jabbed in veins, rather than muscle tissue. 1. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/myocarditis.html https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/my... 2. https://www.bbc.com/news/world-asia-58380867 https://www.bbc.com/news/world-asia-58380867
      - nomel 5y ago
        No need to downvote. I'm not anti-vax, but I'm also not anti-science. The virologist, Vincent Racaniello, has a great podcast on YouTube. He has talked about this a few times. From my understanding of what he said, the spike protein created by infection, and with the vaccines, can "bind" proteins together, causing the myocarditis. There's speculation that this might be related to some of the cognitive problems of coronavirus, also. Approval doesn't mean absolute safety, since that's absolutely impossible to achieve. This is considered acceptable (as shown by the CDC page listing it as a risk), since an actual infection is worse, for most.
eganist 5y ago
> Thus, optimally elicited human polyclonal antibodies against SARS-CoV-2 should be resilient to substantial future SARS-CoV-2 variation and may confer protection against potential future sarbecovirus pandemics. So if I'm extrapolating correctly: any vaccine which can stimulate production of this or similar polyclonal antibodies should prove exceptionally difficult for the virus to overcome through evolutionary pressure. Anyone more intelligent than me on this topic able to help me understand how likely this is to come to fruition?
- eightysixfour 5y ago
  My, admittedly limited, understanding is that the immuno response to a natural infection is "broader" and targets more of the viral proteins ("we show that multiple neutralizing epitopes, within and outside the receptor binding domain (RBD), are variably targeted by human polyclonal antibodies") while the vaccine only introduces a single or small number of proteins for the immune system to respond to. If that is the case then we would want vaccines that include more mRNA instructions for creating more unique viral proteins to expand the number our immune system has been exposed to. I have no idea how challenging that is.
  - gatronicus 5y ago
    > I have no idea how challenging that is. Technically it's easy, Moderna already has multi target vaccines (for other diseases), one with 7 different targets. It can be as easy as literally creating 7 different vaccine liquids and then mixing them all in a single vial. The problem is deciding what to put in, what ratio, possible side effects, etc... Lots of combinations which can mean lots of expensive and slow clinical trials.
  - esyir 5y ago
    That's roughly my understanding of this as well, pulling from whatever I remember from old immunology classes. The human adaptive immune response is massively parallel, and you can liken it to multiple progressive selection rounds for antibody candidates. As such, it is intuitive that this process would create a set of antibodies that targets not just a single antigen in multiple ways, but multiple antigens in multiple ways, resulting in more robust response (see polyclonal b-cell response) As for the latter, the issue, as already stated, is in understanding the side effects and efficacy profiles of said vaccine. Clinical trials are long and expensive processes.
spywaregorilla 5y ago
So... sort of like the inverse of crop monoculture problems?
walterbell 5y ago
This Rockefeller University study is about blood/serum antibodies. It would be good to compare with the efficacy of nasal/mucosal antibodies in individuals who recovered from Covid infection, which could stop infection in the upper respiratory tract before reaching blood.
- tomrod 5y ago
  Do they typically differ?
  - walterbell 5y ago
    From a recent BBC article on immunity, https://www.bbc.com/news/health-58270098 https://www.bbc.com/news/health-58270098 > There is a whole different suite of antibodies (known as immunoglobulin As) in the nose and lungs, compared with those (immunoglobulin Gs) that we measure in the blood. The former is more important as a barrier to infection. Natural infection, because it is in the nose rather than a jab in the arm, may be a better route to those antibodies, and nasal vaccines are being investigated too. Existing vaccines prioritize reducing the risk of illness after infection, rather than stopping infection in the first place. CDC updated their vaccine definition in Sept. 2021, to make this distinction clearer.
polishdude20 5y ago
Slightly off topic but are there any books one can recommend for understanding how this stuff works biologically?
- rolph 5y ago
  any human immunology text [e.g.] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872131/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872131/ molecular biology specific to coronavirus https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7131312/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7131312/ sars specific literature https://www.dovepress.com/understanding-the-molecular-biology-of-sars-cov-2-and-the-covid-19-pan-peer-reviewed-fulltext-article-IDR https://www.dovepress.com/understanding-the-molecular-biolog... https://www.nature.com/articles/s41579-020-00468-6?error=cookies_not_supported&code=e270ded1-920c-4388-8a01-b363630fca17 https://www.nature.com/articles/s41579-020-00468-6?error=coo...
- walterbell 5y ago
  For edutainment, there's a manga/anime called Cells at Work (https://mangarock.to/manga/1684/cells-at-work/first-chapter#lg=1&slide=0 https://mangarock.to/manga/1684/cells-at-work/first-chapter#...) whose final (June 2021) installment covers Covid-19. Includes a character called Killer T Cell, https://cellsatwork.fandom.com/wiki/Killer_T_Cell_(Squad_Leader) https://cellsatwork.fandom.com/wiki/Killer_T_Cell_(Squad_Lea... > Killer T Cell is loud, obnoxious, and quick-tempered, resulting in rivalries with many cells. He also despises it when a non-white blood cell forms a friendship or relationship with one of his kind. As an immature thymocyte he went through training at Thymus school, where apprentice cells like himself learn to become Mature Thymocytes. Season 1 is streaming: https://www.netflix.com/title/81028791 https://www.netflix.com/title/81028791
- esyir 5y ago
  I enjoyed Janeway's Immunology back when I was in university. It's towards the more technical side of the spectrum (textbook), but I remember it being fairly comprehensive for the early bits.
elromulous 5y ago
Can someone who's more knowledgeable on the topic comment on the following: if natural immunity is more robust (as one would expect - the immune system is exposed to many spikes that way, as opposed to just the one), why don't we first immunize with the vaccine, and then expose people to the alpha variant, so as to develop a more robust (i.e. natural) response without the risk.
- Larrikin 5y ago
  No vaccine is 100% effective and it is unethical to purposefully expose people to disease.
  - gfodor 5y ago
    Huh? The ethics of therapies that expose people to pathogens is complicated - many examples where exposure can be ethical as long as patient is aware of the risks. Arguably all vaccines fall into this ethical framework, and other immunizations which involve exposure.
  - dcow 5y ago
    Under what ethical framework?
    - sasquatch69 5y ago
      10x to 100x less likely but still a distinct possibility you kill someone that would've lived if they weren't inoculated with a live virus. That's messed up by itself, but also cases like that would likely discourage the people on the fence about vaccination. https://www.nytimes.com/interactive/2021/08/10/us/covid-breakthrough-infections-vaccines.html https://www.nytimes.com/interactive/2021/08/10/us/covid-brea... Minor live infections to build immunity is called variolation, it's a tactic that was used effectively historically against smallpox, but effectively got obsoleted by vaccination, which doesn't kill as many people. https://en.wikipedia.org/wiki/Variolation https://en.wikipedia.org/wiki/Variolation
      - 5y ago
astockwell 5y ago
Maybe… maybe we _don’t_ deliberately try to create super-mutant-covid right now guys?

72 points by SubiculumCode 5y ago

This is interesting! > By aggregating VOC-associated and antibody-selected spike substitutions into a single polymutant spike protein, we show that 20 naturally occurring mutations in SARS-CoV-2 spike are sufficient to generate pseudotypes with near-complete resistance to the polyclonal neutralizing antibodies generated by convalescents or mRNA vaccine recipients So there are 20 known potential mutations which, when all put together, creates a virus that would be nearly completely resistant to existing vaccinations. > however, plasma from individuals who had been infected and subsequently received mRNA vaccination, neutralized pseudotypes bearing this highly resistant SARS-CoV-2 polymutant spike, or diverse sarbecovirus spike proteins. So, perhaps unsurprisingly, if you've had the virus and then received a vaccine, it appears that you have a very high level of immunity, including to future potential variants. I cannot pull the paper itself, did they test people who were breakthrough cases following vaccination (instead of infection then vaccination)?

neurobashing 5y ago
I think we need the denominator here to put '20' into context. 20 out of 100 million possible mutations is, meh, I'll take those odds. 20 out of 100, well, that's something else entirely, isn't it.
- eightysixfour 5y ago
  Edited because a correction by another user helps to clarify - it is not about the 20 mutations (which they created a mutant spike will all 20 of them!) though, it is more about what was and was not effective in defendening against the mutant spike.
  - hadlock 5y ago
    Coronaviruses are RNA viruses, so there's only a single copy of the genetic material, vs DNA with two copies. The result of RNA viruses is that they typically mutate at a much higher rate than DNA viruses. There are viruses that mutate faster than Coronaviruses, though.
twofornone 5y ago
>So, perhaps unsurprisingly, if you've had the virus and then received a vaccine, it appears that you have a very high level of immunity Why would someone get vaccinated post infection?
- gameswithgo 5y ago
  For more robust immunity, many people do this.
  - ngvrnd 5y ago
    it is in fact recommended.
    - scoot 5y ago
      But apparently not effective in all cases. A friend of mine in their early 20s has Covid a second time, having been vaccinated after their first infection. (To catch it once is unfortunate...)
      - rednerrus 5y ago
        But these are outliers, right?
      - amirhirsch 5y ago
        I don't know why your comment bothers me so much, but... No, your friend didn't have COVID a second time after being vaccinated after their first infection. Especially lacking any clarification that they were in fact tested positive both times, you are merely contributing to noise on the internet. 1) "a friend of yours" is not a data point on which others should base their worldview (unless their testicles got huge and their fiance called it off, why even share?) 2) reinfection is rare 3) it is likely the first time they think they had covid, they weren't tested, and actually had the flu. Here is the CDC information on reinfection: https://www.cdc.gov/coronavirus/2019-ncov/your-health/reinfection.html https://www.cdc.gov/coronavirus/2019-ncov/your-health/reinfe... As of August 6, 2021, the CDC has nothing conclusive to say on the matter: "Cases of reinfection with COVID-19 have been reported, but remain rare . " Anecdotes are noise, and I would encourage you to do no further research.
zmmmmm 5y ago
You chopped off a crucial part of the sentence that completely changes its meaning. The real sentence is: > By aggregating VOC-associated and antibody-selected spike substitutions into a single polymutant spike protein, we show that 20 naturally occurring mutations Aggregating ... into a polymutant spike. That means they put all 20 mutations together, each of them carefully selected from variants of concern or antibody attachment sites, into one single spike protein. Basically they created the most crazy supermutant resistent spike they could. The chance of which would be astronomically small in nature. And their conclusion is that even then a good dose of vaccine allows the body to eliminate it.
- eightysixfour 5y ago
  Thanks, you're right and I've updated it to clarify. > And their conclusion is that even then a good dose of vaccine allows the body to eliminate it. That's not the same thing I got from the conclusion, it sounded like you needed to have a previous infection + the vaccine to clear it. What am I missing?
- robrenaud 5y ago
  Did I misread? This super spike protein defeats merely the vaccinated, but not the naturally infected and then vaccinated, AFAIU.
- openasocket 5y ago
  Additionally, could that even happen naturally? Since viruses only reproduce asexually, there's no way for multiple strain's mutations to somehow be combined together, right?
  - xbkingx 5y ago
    I think it's more of an emergent pattern. Mutant ABC is the target. First Mutant A becomes the predominant strain. There might be some Mutant AB or AC in the population, but the controlling factor is currently Mutant A. Eventually, Mutant A therapies/vaccines are introduced and Mutant A starts to lose its hold. Mutant AB isn't treated by the new treatments (or they're less effective, or Mutant AB goes undetected longer, etc.). Mutant AB becomes king of the hill. Repeat with Mutant ABC. All this would assume that there's no Mutant B or Mutant BC or Mutant AC that increases in prevalence. All the mutations would have to build up over time or occur simultaneously by coincidence (or you could get a combination). It's just basic evolution - organism follows the niche. We have a hard time recognizing it because generation turnover is so rapid. Instead of taking ~30 years for 2.5 offspring, it's a few days for millions of offspring. I don't think mode of reproduction matters much when we're talking at this scale. While the virus creates stable clones across generations, I would think they're more susceptible to mutations and any viable mutation is quickly amplified exponentially. Just like the old high school bio experiment to demonstrate antibiotic resistance, only your respiratory mucus membranes are the medium. Those bacteria reproduced asexually.
dougmwne 5y ago
They only tested the plasma from people who were infected, people vaccinated with Pfizer, and people who were infected, then vaccinated. The 20 mutations they mention was a set of 20 mutations to a single spike protein that they then attached to a carrier virus to test plasma neutralization. It's not the full space of possible mutations that could cause immunity escape, but it is one that they found with a plausibly low number of mutations that it could occur in the wild that would result is almost total escape for vaccinated or previously infected. An interesting result was that the infected then vaccinated individuals developed antibodies that targeted a very broad range of coronaviruses, including their engineered virus, delta, many other variants, and the original SARS. It's suggested that future vaccines could be engineered to produce this broad immunity. The immune system is almost terrifyingly complex.
- devin 5y ago
  > An interesting result was that the infected then vaccinated individuals developed antibodies that targeted a very broad range of coronaviruses, including their engineered virus, delta, many other variants, and the original SARS. Glad you brought this up, but from what I understand this isn't actually all that interesting (read: surprising). mRNA vaccines target the spike protein because it's functional and well-conserved. Natural infection means your immune system sees many more proteins.
  - dougmwne 5y ago
    Yes, but natural infection did not produce this broad immunity in their samples, only infected then vaccinated developed this special kind of broad immunity. That is supprising in a way, that we could coax the immune system into producing a special kind of immunity that wouldn't otherwise be likely to occur naturally. It opens an area of research into what mRNA sequence or dosing regimen could reproduce this immunity for a future super vaccine.
    - angelzen 5y ago
      Natural infection was one event vs. natural infection + vaccine being two events separated by a time interval. It may be that we are stumbling upon a natural mechanism that makes recurring infections almost impossible past 2nd event.
bpodgursky 5y ago
Given the... possible... origins of this virus, I hope they are being exceedingly careful about actually synthesizing a virus with all of these mutations at once. Or they stand a very high risk of creating and releasing the doomsday variant they are worried about in the first place...
- kmeisthax 5y ago
  I think they only synthesized the spike proteins, not the whole virus. You don't need a whole virus to check if a protein is neutralized or not. (For the record, if spike proteins were themselves in any way harmful to life on their own, Moderna and Pfizer wouldn't be the primary vaccine vendors for the US right now.)
  - nomel 5y ago
    > in any way harmful to life on their own I think it's fairly well accepted that they can cause myocarditis [1], which has killed some [2]. Better than getting the virus, but they appear to be capable of harm. I've naively wondered if the young men are getting jabbed in veins, rather than muscle tissue. 1. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/myocarditis.html https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/my... 2. https://www.bbc.com/news/world-asia-58380867 https://www.bbc.com/news/world-asia-58380867
    - nomel 5y ago
      No need to downvote. I'm not anti-vax, but I'm also not anti-science. The virologist, Vincent Racaniello, has a great podcast on YouTube. He has talked about this a few times. From my understanding of what he said, the spike protein created by infection, and with the vaccines, can "bind" proteins together, causing the myocarditis. There's speculation that this might be related to some of the cognitive problems of coronavirus, also. Approval doesn't mean absolute safety, since that's absolutely impossible to achieve. This is considered acceptable (as shown by the CDC page listing it as a risk), since an actual infection is worse, for most.

eganist 5y ago

> Thus, optimally elicited human polyclonal antibodies against SARS-CoV-2 should be resilient to substantial future SARS-CoV-2 variation and may confer protection against potential future sarbecovirus pandemics. So if I'm extrapolating correctly: any vaccine which can stimulate production of this or similar polyclonal antibodies should prove exceptionally difficult for the virus to overcome through evolutionary pressure. Anyone more intelligent than me on this topic able to help me understand how likely this is to come to fruition?

eightysixfour 5y ago
My, admittedly limited, understanding is that the immuno response to a natural infection is "broader" and targets more of the viral proteins ("we show that multiple neutralizing epitopes, within and outside the receptor binding domain (RBD), are variably targeted by human polyclonal antibodies") while the vaccine only introduces a single or small number of proteins for the immune system to respond to. If that is the case then we would want vaccines that include more mRNA instructions for creating more unique viral proteins to expand the number our immune system has been exposed to. I have no idea how challenging that is.
- gatronicus 5y ago
  > I have no idea how challenging that is. Technically it's easy, Moderna already has multi target vaccines (for other diseases), one with 7 different targets. It can be as easy as literally creating 7 different vaccine liquids and then mixing them all in a single vial. The problem is deciding what to put in, what ratio, possible side effects, etc... Lots of combinations which can mean lots of expensive and slow clinical trials.
- esyir 5y ago
  That's roughly my understanding of this as well, pulling from whatever I remember from old immunology classes. The human adaptive immune response is massively parallel, and you can liken it to multiple progressive selection rounds for antibody candidates. As such, it is intuitive that this process would create a set of antibodies that targets not just a single antigen in multiple ways, but multiple antigens in multiple ways, resulting in more robust response (see polyclonal b-cell response) As for the latter, the issue, as already stated, is in understanding the side effects and efficacy profiles of said vaccine. Clinical trials are long and expensive processes.

spywaregorilla 5y ago

So... sort of like the inverse of crop monoculture problems?

walterbell 5y ago

This Rockefeller University study is about blood/serum antibodies. It would be good to compare with the efficacy of nasal/mucosal antibodies in individuals who recovered from Covid infection, which could stop infection in the upper respiratory tract before reaching blood.

tomrod 5y ago
Do they typically differ?
- walterbell 5y ago
  From a recent BBC article on immunity, https://www.bbc.com/news/health-58270098 https://www.bbc.com/news/health-58270098 > There is a whole different suite of antibodies (known as immunoglobulin As) in the nose and lungs, compared with those (immunoglobulin Gs) that we measure in the blood. The former is more important as a barrier to infection. Natural infection, because it is in the nose rather than a jab in the arm, may be a better route to those antibodies, and nasal vaccines are being investigated too. Existing vaccines prioritize reducing the risk of illness after infection, rather than stopping infection in the first place. CDC updated their vaccine definition in Sept. 2021, to make this distinction clearer.

polishdude20 5y ago

Slightly off topic but are there any books one can recommend for understanding how this stuff works biologically?

rolph 5y ago
any human immunology text [e.g.] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872131/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872131/ molecular biology specific to coronavirus https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7131312/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7131312/ sars specific literature https://www.dovepress.com/understanding-the-molecular-biology-of-sars-cov-2-and-the-covid-19-pan-peer-reviewed-fulltext-article-IDR https://www.dovepress.com/understanding-the-molecular-biolog... https://www.nature.com/articles/s41579-020-00468-6?error=cookies_not_supported&code=e270ded1-920c-4388-8a01-b363630fca17 https://www.nature.com/articles/s41579-020-00468-6?error=coo...
walterbell 5y ago
For edutainment, there's a manga/anime called Cells at Work (https://mangarock.to/manga/1684/cells-at-work/first-chapter#lg=1&slide=0 https://mangarock.to/manga/1684/cells-at-work/first-chapter#...) whose final (June 2021) installment covers Covid-19. Includes a character called Killer T Cell, https://cellsatwork.fandom.com/wiki/Killer_T_Cell_(Squad_Leader) https://cellsatwork.fandom.com/wiki/Killer_T_Cell_(Squad_Lea... > Killer T Cell is loud, obnoxious, and quick-tempered, resulting in rivalries with many cells. He also despises it when a non-white blood cell forms a friendship or relationship with one of his kind. As an immature thymocyte he went through training at Thymus school, where apprentice cells like himself learn to become Mature Thymocytes. Season 1 is streaming: https://www.netflix.com/title/81028791 https://www.netflix.com/title/81028791
esyir 5y ago
I enjoyed Janeway's Immunology back when I was in university. It's towards the more technical side of the spectrum (textbook), but I remember it being fairly comprehensive for the early bits.

elromulous 5y ago

Can someone who's more knowledgeable on the topic comment on the following: if natural immunity is more robust (as one would expect - the immune system is exposed to many spikes that way, as opposed to just the one), why don't we first immunize with the vaccine, and then expose people to the alpha variant, so as to develop a more robust (i.e. natural) response without the risk.

Larrikin 5y ago
No vaccine is 100% effective and it is unethical to purposefully expose people to disease.
- gfodor 5y ago
  Huh? The ethics of therapies that expose people to pathogens is complicated - many examples where exposure can be ethical as long as patient is aware of the risks. Arguably all vaccines fall into this ethical framework, and other immunizations which involve exposure.
- dcow 5y ago
  Under what ethical framework?
  - sasquatch69 5y ago
    10x to 100x less likely but still a distinct possibility you kill someone that would've lived if they weren't inoculated with a live virus. That's messed up by itself, but also cases like that would likely discourage the people on the fence about vaccination. https://www.nytimes.com/interactive/2021/08/10/us/covid-breakthrough-infections-vaccines.html https://www.nytimes.com/interactive/2021/08/10/us/covid-brea... Minor live infections to build immunity is called variolation, it's a tactic that was used effectively historically against smallpox, but effectively got obsoleted by vaccination, which doesn't kill as many people. https://en.wikipedia.org/wiki/Variolation https://en.wikipedia.org/wiki/Variolation
    - 5y ago

astockwell 5y ago

Maybe… maybe we _don’t_ deliberately try to create super-mutant-covid right now guys?