5 ms·

I am good friends with 3 doctors, and talk to them a lot about the amazing science behind the vaccines and the incredible speed with which those were designed a

I am good friends with 3 doctors, and talk to them a lot about the amazing science behind the vaccines and the incredible speed with which those were designed and developed. All agree it was done at pretty much the software speed - custom designed on the computer in weeks and then built to order - and both them and I think it's pretty neat. It is very refreshing to talk to them because they, being good doctors, deal calmly and reasonably with probabilities rather than absolutes. Very early, even before general public could get vaccines, all 3 of them told me to expect something like that - the virus mutates, it is expected to develop, the mutation for reproductive number going up is likely to occur - and it did - and the vaccines will likely be needing to adjust. Even the highest levels of vaccination are no protection, and I am pretty tiny Israel in a sea of the largely unvaccinated is going to be swamped.

graderjs 5y ago
I don't know if we have this, but it would be good if we had a technology that enhanced your body's immune system to identify and kill viruses, rather than prime it to respond to a particular viral signal, that then may need to be updated as the virus changes (that's how I understand how vaccines work, but that could be false). You might think it's a subtle difference, but I think the former technology would be leaning into the body's existing ability to form a variety of antigens for viruses it encounters, and boosting its defense/offense against those, rather than 'handing out a series of police composite sketches', and saying 'Be On the Look Out for this specific guy, he might be coming through here.' The former could be more alike to enhancing predictive policing and profiling abilities, and beefing up response and enforcement capabilities.
- thatguy0900 5y ago
  Beefing up the immune system without garunteeing it something to do seems like a recipe for autoimmune disorders, no?
  - graderjs 5y ago
    Yeah, agree. It would be tricky. I'm hoping that by 'enhancing' the immune system you lean into its natural self-regulation equilibrium system and avoid that mostly--but then again autoimmune disorders seemingly emerge from those stasis systems going haywire, maybe without external poking...so it would be tricky for sure. I guess the intuition is that the human immune system is an incredibly sophisticated, evolving capability that over time, and over the mass population, can respond to become resilient against a wide array of pathogens. So if you could somehow capture the best of that (like, for illustration, take the immune system of the healthiest, most resilient person, 30 generations from now in the future) and convey that benefit to many other people, that would be truly awesome. Sort of like an idea of training an AI, more iterations are better, the immune system of any one person at any one point in time, might not be so great, but the best immune system of the population after encountering many pathogens, is going to be really great. How can we short circuit that "natural training" process and enhance the immune system? But I agree that attempts to do so might run the risk of creating or exacerbating autoimmune diseases...But I still think it's worth it.
- lamontcg 5y ago
  The immune system already does that and its the responsibility of CD4+ helper T-cells. The 2009 pandemic was significantly blunted because people born before 1957 had partial immunity from cross-reactive T-cells to H1N1 which was endemic in humans from 1918-1957. So after mutating in probably billions of pigs for 50 years the H1N1 virus that hopped back to humans was still sufficiently recognized by the immune system of older people to take any edge off of that pandemic. I'm also fairly skeptical of the data coming out of Israel about waning immunity. Everyone is taking that data at face value while entirely ignoring the disclaimer: "(Potential confounders include the fact that the very oldest Israelis, with the weakest immune systems, were vaccinated first.)". We really need a lot better data on much better matched cohorts to determine actual immune waning in the presence of the same viral variant.
  - graderjs 5y ago
    Oh yeah definitely of course the immune system that already does that, the idea is just enhance its ability so that everyone has sort of Best in class defence against these viruses. it can be kind of slow on an individual level, but on a population level you will have some people who have evolved better defenses, or more resilient immune systems. If we can share that around that's the idea. It's very interesting though about that immunity thing you say. People born then.
    - grepfru_it 5y ago
      I think that was the idea that spurred monoclonal antibodies https://en.wikipedia.org/wiki/Monoclonal_antibody https://en.wikipedia.org/wiki/Monoclonal_antibody
      - graderjs 5y ago
        Interesting, thanks. :)
criticaltinker 5y ago
> all 3 of them told me to expect something like that - the virus mutates ... and the vaccines will likely be needing to adjust Your doctor friends were informing you about a phenomenon commonly referred to as "immune escape". The current mRNA based SARS-CoV-2 vaccines are effective at preventing severe outcomes like hospitalization and death. However, they do not necessarily prevent infection or transmission - and they induce an immune response highly targeted toward the spike protein RBD [1]. Combined with mass vaccination strategies, these factors contribute to a situation that exerts tremendous selective pressure on the virus, and can result in convergent mutations that are advantageous for the virus in a large population of people [1][2]. These mutations can lead to partial or complete immune escape, which manifests as increased transmission or virulence, reduced vaccine efficacy, and reduced immunity in naturally infected individuals. > Even the highest levels of vaccination are no protection It's not quite accurate to say "are no protection". I would rephrase as: Strategies for viral elimination should therefore be diversified across molecular targets and therapeutic modalities [1] [1] Risk of rapid evolutionary escape from biomedical interventions targeting SARS-CoV-2 spike protein https://pubmed.ncbi.nlm.nih.gov/33909660/ https://pubmed.ncbi.nlm.nih.gov/33909660/ [2] SARS-CoV-2 immune evasion by the B.1.427/B.1.429 variant of concern https://science.sciencemag.org/content/early/2021/06/30/science.abi7994 https://science.sciencemag.org/content/early/2021/06/30/scie...
- maxerickson 5y ago
  The Delta variant emerged prior to widespread vaccination.
  - criticaltinker 5y ago
    Yes the delta variant may have originated prior to widespread vaccination, but the dominance of the delta variant (and other VOCs) did coincide with mass vaccination campaigns. Please see the first source I cited if you're interested in these ideas and want to hear more straight from the experts: > "The spike protein receptor-binding domain (RBD) of SARS-CoV-2 is the molecular target for many vaccines and antibody-based prophylactics aimed at bringing COVID-19 under control." [1] > "Such a narrow molecular focus raises the specter of viral immune evasion as a potential failure mode for these biomedical interventions. With the emergence of new strains of SARS-CoV-2 with altered transmissibility and immune evasion potential, a critical question is this: how easily can the virus escape neutralizing antibodies (nAbs) targeting the spike RBD?" [1] > "Our modeling suggests that SARS-CoV-2 mutants with one or two mildly deleterious mutations are expected to exist in high numbers due to neutral genetic variation, and consequently resistance to vaccines or other prophylactics that rely on one or two antibodies for protection can develop quickly -and repeatedly- under positive selection." [1] > "The speed at which nAb resistance develops in the population increases substantially as the number of infected individuals increases, suggesting that complementary strategies to prevent SARS-CoV-2 transmission that exert specific pressure on other proteins (e.g., antiviral prophylactics) or that do not exert a specific selective pressure on the virus (e.g., high-efficiency air filtration, masking, ultraviolet air purification) are key to reducing the risk of immune escape" [1] > "Strategies for viral elimination should therefore be diversified across molecular targets and therapeutic modalities" [1]
deleted 5y ago
[deleted]

graderjs 5y ago

I don't know if we have this, but it would be good if we had a technology that enhanced your body's immune system to identify and kill viruses, rather than prime it to respond to a particular viral signal, that then may need to be updated as the virus changes (that's how I understand how vaccines work, but that could be false). You might think it's a subtle difference, but I think the former technology would be leaning into the body's existing ability to form a variety of antigens for viruses it encounters, and boosting its defense/offense against those, rather than 'handing out a series of police composite sketches', and saying 'Be On the Look Out for this specific guy, he might be coming through here.' The former could be more alike to enhancing predictive policing and profiling abilities, and beefing up response and enforcement capabilities.

thatguy0900 5y ago
Beefing up the immune system without garunteeing it something to do seems like a recipe for autoimmune disorders, no?
- graderjs 5y ago
  Yeah, agree. It would be tricky. I'm hoping that by 'enhancing' the immune system you lean into its natural self-regulation equilibrium system and avoid that mostly--but then again autoimmune disorders seemingly emerge from those stasis systems going haywire, maybe without external poking...so it would be tricky for sure. I guess the intuition is that the human immune system is an incredibly sophisticated, evolving capability that over time, and over the mass population, can respond to become resilient against a wide array of pathogens. So if you could somehow capture the best of that (like, for illustration, take the immune system of the healthiest, most resilient person, 30 generations from now in the future) and convey that benefit to many other people, that would be truly awesome. Sort of like an idea of training an AI, more iterations are better, the immune system of any one person at any one point in time, might not be so great, but the best immune system of the population after encountering many pathogens, is going to be really great. How can we short circuit that "natural training" process and enhance the immune system? But I agree that attempts to do so might run the risk of creating or exacerbating autoimmune diseases...But I still think it's worth it.
lamontcg 5y ago
The immune system already does that and its the responsibility of CD4+ helper T-cells. The 2009 pandemic was significantly blunted because people born before 1957 had partial immunity from cross-reactive T-cells to H1N1 which was endemic in humans from 1918-1957. So after mutating in probably billions of pigs for 50 years the H1N1 virus that hopped back to humans was still sufficiently recognized by the immune system of older people to take any edge off of that pandemic. I'm also fairly skeptical of the data coming out of Israel about waning immunity. Everyone is taking that data at face value while entirely ignoring the disclaimer: "(Potential confounders include the fact that the very oldest Israelis, with the weakest immune systems, were vaccinated first.)". We really need a lot better data on much better matched cohorts to determine actual immune waning in the presence of the same viral variant.
- graderjs 5y ago
  Oh yeah definitely of course the immune system that already does that, the idea is just enhance its ability so that everyone has sort of Best in class defence against these viruses. it can be kind of slow on an individual level, but on a population level you will have some people who have evolved better defenses, or more resilient immune systems. If we can share that around that's the idea. It's very interesting though about that immunity thing you say. People born then.
  - grepfru_it 5y ago
    I think that was the idea that spurred monoclonal antibodies https://en.wikipedia.org/wiki/Monoclonal_antibody https://en.wikipedia.org/wiki/Monoclonal_antibody
    - graderjs 5y ago
      Interesting, thanks. :)

criticaltinker 5y ago

> all 3 of them told me to expect something like that - the virus mutates ... and the vaccines will likely be needing to adjust Your doctor friends were informing you about a phenomenon commonly referred to as "immune escape". The current mRNA based SARS-CoV-2 vaccines are effective at preventing severe outcomes like hospitalization and death. However, they do not necessarily prevent infection or transmission - and they induce an immune response highly targeted toward the spike protein RBD [1]. Combined with mass vaccination strategies, these factors contribute to a situation that exerts tremendous selective pressure on the virus, and can result in convergent mutations that are advantageous for the virus in a large population of people [1][2]. These mutations can lead to partial or complete immune escape, which manifests as increased transmission or virulence, reduced vaccine efficacy, and reduced immunity in naturally infected individuals. > Even the highest levels of vaccination are no protection It's not quite accurate to say "are no protection". I would rephrase as: Strategies for viral elimination should therefore be diversified across molecular targets and therapeutic modalities [1] [1] Risk of rapid evolutionary escape from biomedical interventions targeting SARS-CoV-2 spike protein https://pubmed.ncbi.nlm.nih.gov/33909660/ https://pubmed.ncbi.nlm.nih.gov/33909660/ [2] SARS-CoV-2 immune evasion by the B.1.427/B.1.429 variant of concern https://science.sciencemag.org/content/early/2021/06/30/science.abi7994 https://science.sciencemag.org/content/early/2021/06/30/scie...

maxerickson 5y ago
The Delta variant emerged prior to widespread vaccination.
- criticaltinker 5y ago
  Yes the delta variant may have originated prior to widespread vaccination, but the dominance of the delta variant (and other VOCs) did coincide with mass vaccination campaigns. Please see the first source I cited if you're interested in these ideas and want to hear more straight from the experts: > "The spike protein receptor-binding domain (RBD) of SARS-CoV-2 is the molecular target for many vaccines and antibody-based prophylactics aimed at bringing COVID-19 under control." [1] > "Such a narrow molecular focus raises the specter of viral immune evasion as a potential failure mode for these biomedical interventions. With the emergence of new strains of SARS-CoV-2 with altered transmissibility and immune evasion potential, a critical question is this: how easily can the virus escape neutralizing antibodies (nAbs) targeting the spike RBD?" [1] > "Our modeling suggests that SARS-CoV-2 mutants with one or two mildly deleterious mutations are expected to exist in high numbers due to neutral genetic variation, and consequently resistance to vaccines or other prophylactics that rely on one or two antibodies for protection can develop quickly -and repeatedly- under positive selection." [1] > "The speed at which nAb resistance develops in the population increases substantially as the number of infected individuals increases, suggesting that complementary strategies to prevent SARS-CoV-2 transmission that exert specific pressure on other proteins (e.g., antiviral prophylactics) or that do not exert a specific selective pressure on the virus (e.g., high-efficiency air filtration, masking, ultraviolet air purification) are key to reducing the risk of immune escape" [1] > "Strategies for viral elimination should therefore be diversified across molecular targets and therapeutic modalities" [1]

deleted 5y ago

[deleted]