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Reference [1] is applicable to how our body handles an immune response to the viral infection in general: i.e. whether naturally acquired, or through controlled

by bmer 5y ago

Reference [1] is applicable to how our body handles an immune response to the viral infection in general: i.e. whether naturally acquired, or through controlled vaccination. Natural infections were, naturally focused upon, in order to understand the baseline dynamics of viral infection. Reference [2] is...it says just as much about the efficacy of vaccination as the efficacy of natural immunity: > The cumulative incidence of SARS-CoV-2 infection remained almost zero among previously infected unvaccinated subjects, previously infected subjects who were vaccinated, and previously uninfected subjects who were vaccinated, compared with a steady increase in cumulative incidence among previously uninfected subjects who remained unvaccinated. Read reference [3] to understand why natural immunity doesn't cut it. Note that widespread natural immunity causes the same positive selection pressure as widespread vaccine deployment, and: > Finally, our work suggests that immune evasion requiring one to two mutations occurs within months, raising the prospect that this phenomenon will further shorten the duration of natural immunity... The paper goes on to provide (under Discussion) a series of strategies for developing a vaccination system that takes into account modelled viral evolution. Can't come up with strategies like that for natural immunity, apart from: "periodically re-infect individual"...which is exactly what vaccines do, in a controlled manner. Reference [4] and [5] are research tabulating mutations the virus is undergoing to counter both natural acquired and vaccine-mediated immune responses. It is not an indictment against vaccines, but just like paper [3], provide strategies on how to update vaccines. That updates will be required is not a surprise to anyone. Viral evolution has long been known of, and no one expected the emergency COVID-19 vaccines to be effective until the end of time. Reference [6]...did you read it? It's about vaccines which protect the host(keep them alive), but still keep them infectious (capable of transmission). None of the COVID-19 vaccines do that...

criticaltinker 5y ago
Are you trying to refute the claim that natural infection confers immunity that is at least equally as protective as vaccination? It's not clear to me that you've presented any counter evidence. I will try to outline my thoughts on your comment to help the discussion. [1] is another primary source beyond the OP that demonstrates the durability of the immune response from natural infection. We are in agreement that in principle the immune response from vaccination should also be durable due to relying on the same underlying mechanisms of the immune system - in fact I am unaware of any literature which demonstrates otherwise. So your point about [1] doesn't seem particularly relevant to me. > Reference [2] is...it says just as much about the efficacy of vaccination as the efficacy of natural immunity Yes you're right, and that is a relevant quote you pulled from the abstract. Again, I think we're actually in agreement here - the findings support my original claims. > Read reference [3] to understand why natural immunity doesn't cut it. Note that widespread natural immunity causes the same positive selection pressure as widespread vaccine deployment You seem to be missing the central thesis of [3], here are the relevant excerpts: - "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." - "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?" - "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." - "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" - "Strategies for viral elimination should therefore be diversified across molecular targets and therapeutic modalities" We are in agreement [4] and [5] are not an indictment against vaccines - but again you seem to be missing the most important and highly relevant findings which support my claims. For example from [4]: - "The acquisition of the L452R substitution by multiple lineages across multiple continents, including the B.1.617.1 and B.1.617.2 lineages emerging in India (54), is suggestive of positive selection, which might result from the selective pressure of RBD-specific neutralizing Abs" - "Our data support that the SARS-CoV-2 NTD evolved a compensatory mechanism to form an alternative disulfide bond and that mutations of the S signal peptide occur in vivo in a clinical setting to promote immune evasion." - "Understanding the newly found mechanism of immune evasion in emerging SARS-CoV-2 variants, such as the signal peptide modification described herein, is as important as sequence surveillance itself to successfully counter the ongoing pandemic." For example from [5]: - "different individuals immunized with the Moderna (mRNA-1273) or Pfizer–BioNTech (BNT162b2) vaccines produce closely related, and nearly identical, antibodies." - "To avert selection and escape, antibody therapies should be composed of combinations of antibodies that target non-overlapping or highly conserved epitopes" - "We speculate that these mutations emerged in response to immune selection in individuals with nonsterilizing immunity." > Reference [6]...did you read it? It's about vaccines which protect the host(keep them alive), but still keep them infectious (capable of transmission). None of the COVID-19 vaccines do that... You are incorrect - the current spike protein focused mRNA based vaccines do not guarantee sterilizing immunity - that means you can be vaccinated yet still get infected and transmit the virus to others. Please cite your sources if you're going to make such claims.
- bmer 5y ago
  I don't see how I'm missing the central thesis of [3]. If a strategy X develops for eliminating a virus Y, Y will undergo positive selection to escape targeting by X. X can be whatever target scheme our immune systems first fixate on, or a narrow targeting emergency vaccine. It really doesn't matter. The researchers focus on the defense mechanism kickstarted by the vaccine, because their point is we cannot be complacent. Point well taken, to be sure, but no one was being complacent anyway (I've seen a fair number of presentations on vaccine design at this point, and no one is touting anything as the silver bullet). Where I'm living, other mechanisms for managing the infection have not disappeared just because vaccination is now in play. The emergency vaccine is first and foremost, a way to generate herd immunity quickly. It will need to be supplemented with other strategies, both in the short term, and in the long term. The researchers have done valuable work in helping us better quantify the timespan over which we can expect escape, and thus allow us to better estimate the time by which we'll need the next wave of solutions in play. THE RESEARCHERS DO NOT ARGUE THAT THE EMERGENCY VACCINE IS USELESS. I said it the first time, and I'll repeat it again: that a more comprehensive vaccine design will need to supplement the emergency vaccine was a given from day 1. For that same reason, design of "upgrades" to the vaccination program began a long time ago. The papers you're citing are collecting data which help such designs. None of them advocated that the emergency vaccination is useless. > You are incorrect - the current spike protein focused mRNA based vaccines do not guarantee sterilizing immunity - that means you can be vaccinated yet still get infected and transmit the virus to others. Please cite your sources if you're going to make such claims. Do you realize that the extent to which vaccinations stop transmission is on a continuum? It is not "on", or "off" in exact terms. The current COVID-19 vaccines immunize to an extent that the re-transmission rate is negligible. A leaky vaccine (the kind studied in the paper) barely makes a dent to the transmission rate, and if it does, only mildly. COVID-19 vaccinations are far from leaky, even if they are not 100% water-tight. I'm not sure why you're using that paper either, to be honest. There are better ones, but they don't suit your point as well, probably? Here's one that directly talks about COVID-19, and openly acknowledges the risk that exists due to the ACTUAL leakiness of the COVID-19 vaccine, but also shows why this does not prevent herd immunity from emerging, and why it in fact poses a greater risk to those who choose to stubbornly remain unvaccinated, or (and more seriously) those who lack the resources to be vaccinated: https://www.medrxiv.org/content/10.1101/2020.12.01.20241836v2 https://www.medrxiv.org/content/10.1101/2020.12.01.20241836v... I'm not going to continue on this conversation, as I went through your other posts, and I have a fair grasp on what your position is. Continuing on trying to talk to you would be extremely stupid on my part. Have fun doing whatever it is you want to, and good luck.

by bmer 5y ago

criticaltinker 5y ago

Are you trying to refute the claim that natural infection confers immunity that is at least equally as protective as vaccination? It's not clear to me that you've presented any counter evidence. I will try to outline my thoughts on your comment to help the discussion. [1] is another primary source beyond the OP that demonstrates the durability of the immune response from natural infection. We are in agreement that in principle the immune response from vaccination should also be durable due to relying on the same underlying mechanisms of the immune system - in fact I am unaware of any literature which demonstrates otherwise. So your point about [1] doesn't seem particularly relevant to me. > Reference [2] is...it says just as much about the efficacy of vaccination as the efficacy of natural immunity Yes you're right, and that is a relevant quote you pulled from the abstract. Again, I think we're actually in agreement here - the findings support my original claims. > Read reference [3] to understand why natural immunity doesn't cut it. Note that widespread natural immunity causes the same positive selection pressure as widespread vaccine deployment You seem to be missing the central thesis of [3], here are the relevant excerpts: - "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." - "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?" - "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." - "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" - "Strategies for viral elimination should therefore be diversified across molecular targets and therapeutic modalities" We are in agreement [4] and [5] are not an indictment against vaccines - but again you seem to be missing the most important and highly relevant findings which support my claims. For example from [4]: - "The acquisition of the L452R substitution by multiple lineages across multiple continents, including the B.1.617.1 and B.1.617.2 lineages emerging in India (54), is suggestive of positive selection, which might result from the selective pressure of RBD-specific neutralizing Abs" - "Our data support that the SARS-CoV-2 NTD evolved a compensatory mechanism to form an alternative disulfide bond and that mutations of the S signal peptide occur in vivo in a clinical setting to promote immune evasion." - "Understanding the newly found mechanism of immune evasion in emerging SARS-CoV-2 variants, such as the signal peptide modification described herein, is as important as sequence surveillance itself to successfully counter the ongoing pandemic." For example from [5]: - "different individuals immunized with the Moderna (mRNA-1273) or Pfizer–BioNTech (BNT162b2) vaccines produce closely related, and nearly identical, antibodies." - "To avert selection and escape, antibody therapies should be composed of combinations of antibodies that target non-overlapping or highly conserved epitopes" - "We speculate that these mutations emerged in response to immune selection in individuals with nonsterilizing immunity." > Reference [6]...did you read it? It's about vaccines which protect the host(keep them alive), but still keep them infectious (capable of transmission). None of the COVID-19 vaccines do that... You are incorrect - the current spike protein focused mRNA based vaccines do not guarantee sterilizing immunity - that means you can be vaccinated yet still get infected and transmit the virus to others. Please cite your sources if you're going to make such claims.

bmer 5y ago
I don't see how I'm missing the central thesis of [3]. If a strategy X develops for eliminating a virus Y, Y will undergo positive selection to escape targeting by X. X can be whatever target scheme our immune systems first fixate on, or a narrow targeting emergency vaccine. It really doesn't matter. The researchers focus on the defense mechanism kickstarted by the vaccine, because their point is we cannot be complacent. Point well taken, to be sure, but no one was being complacent anyway (I've seen a fair number of presentations on vaccine design at this point, and no one is touting anything as the silver bullet). Where I'm living, other mechanisms for managing the infection have not disappeared just because vaccination is now in play. The emergency vaccine is first and foremost, a way to generate herd immunity quickly. It will need to be supplemented with other strategies, both in the short term, and in the long term. The researchers have done valuable work in helping us better quantify the timespan over which we can expect escape, and thus allow us to better estimate the time by which we'll need the next wave of solutions in play. THE RESEARCHERS DO NOT ARGUE THAT THE EMERGENCY VACCINE IS USELESS. I said it the first time, and I'll repeat it again: that a more comprehensive vaccine design will need to supplement the emergency vaccine was a given from day 1. For that same reason, design of "upgrades" to the vaccination program began a long time ago. The papers you're citing are collecting data which help such designs. None of them advocated that the emergency vaccination is useless. > You are incorrect - the current spike protein focused mRNA based vaccines do not guarantee sterilizing immunity - that means you can be vaccinated yet still get infected and transmit the virus to others. Please cite your sources if you're going to make such claims. Do you realize that the extent to which vaccinations stop transmission is on a continuum? It is not "on", or "off" in exact terms. The current COVID-19 vaccines immunize to an extent that the re-transmission rate is negligible. A leaky vaccine (the kind studied in the paper) barely makes a dent to the transmission rate, and if it does, only mildly. COVID-19 vaccinations are far from leaky, even if they are not 100% water-tight. I'm not sure why you're using that paper either, to be honest. There are better ones, but they don't suit your point as well, probably? Here's one that directly talks about COVID-19, and openly acknowledges the risk that exists due to the ACTUAL leakiness of the COVID-19 vaccine, but also shows why this does not prevent herd immunity from emerging, and why it in fact poses a greater risk to those who choose to stubbornly remain unvaccinated, or (and more seriously) those who lack the resources to be vaccinated: https://www.medrxiv.org/content/10.1101/2020.12.01.20241836v2 https://www.medrxiv.org/content/10.1101/2020.12.01.20241836v... I'm not going to continue on this conversation, as I went through your other posts, and I have a fair grasp on what your position is. Continuing on trying to talk to you would be extremely stupid on my part. Have fun doing whatever it is you want to, and good luck.