5 ms·

SARS-CoV-2 Vaccines, Breakthrough Infections and Lasting Natural Immunity

29 points by hudon 5y ago

fifthofhisname 5y ago
It was clear from the start that SARS-CoV-2 would become endemic. Very interesting write up + data here. > Cure-Hub's data shows less antibody diversity in vaccinated individuals than naturally infected individuals. Fewer unique antibodies provide the virus with an avenue for immune escape through S protein mutations. The data compares natural immunity vs vaccinated immunity. I'm curious to see this data compared against individuals who were infected and were then vaccinated vs. individuals who were vaccinated then infected.
- criticaltinker 5y ago
  I have no primary sources to offer regarding this question. But here's some pure speculation if you're interested - assuming immunological memory operates in a 'most recently used' fashion, then it would follow that individuals will develop an immune response that trends toward being most effective at neutralizing the viral profile that was last seen. Consequently, the studies and data that evaluate natural immunity vs vaccinated immunity could be fairly applicable. In practice I'm sure you'd see a blending of the two immune responses, but timing of exposure could play a big factor in weighting that balance.
criticaltinker 5y ago
This blog post from Cure-Hub LLC is not a peer-reviewed primary source, but the claims made within do cite the literature fairly appropriately and accurately. Here I've outlined the most important claims, and where citations were provided, I included excerpts from the cited literature to support the claim. > "multiple studies show that reinfection in people with natural immunity is rare" - "A previous history of SARS-CoV-2 infection was associated with an 84% lower risk of infection, with median protective effect observed 7 months following primary infection. This study shows that previous infection with SARS-CoV-2 induces effective immunity to future infections in most individuals." [1] - "Reinfection is rare in the young and international population of Qatar. Natural infection appears to elicit strong protection against reinfection with an efficacy ~95% for at least seven months." [2] - "To our knowledge, this is the first systematic review to synthesise the evidence on the risk of SARS‐CoV‐2 reinfection over time. [...] Reinfection was an uncommon event (absolute rate 0%–1.1%), with no study reporting an increase in the risk of reinfection over time. [...] These data suggest that naturally acquired SARS‐CoV‐2 immunity does not wane for at least 10 months post‐infection. However, the applicability of these studies to new variants or to vaccine‐induced immunity remains uncertain." [3] - "Cumulative incidence of COVID-19 was examined among 52238 employees in an American healthcare system. COVID-19 did not occur in anyone over the five months of the study among 2579 individuals previously infected with COVID-19, including 1359 who did not take the vaccine. [...] Individuals who have had SARS-CoV-2 infection are unlikely to benefit from COVID-19 vaccination, and vaccines can be safely prioritized to those who have not been infected before." [4] > "Data also suggests that natural immunity is more protective than vaccine related immunity" > "The most significant difference between vaccinated and naturally infected individuals is the antibody response against nucleocapsid (N) protein" The author is basing this claim on the Cure-Hub data, but did not cite any literature on this. The finding is consistent with other papers, for example see [5]. - "The nucleocapsid protein (NP) is an immunodominant antigen for which the antibody response increases in concordance with natural exposure (Figure 2A,3A and 4)." [5] - "However, nucleocapsid is not a component of the mRNA vaccines and consequently there is no vaccine-induced increase in Ab against this antigen. Accordingly, anti-spike antibody levels increased in vaccinees while the nucleocapsid protein Ab level remained constant." [5] > "Cure-Hub's data shows less antibody diversity in vaccinated individuals than naturally infected individuals." > "Fewer unique antibodies provide the virus with an avenue for immune escape through S protein mutations." The author did not cite any literature on this claim either, so I'm providing an example here [6]. - "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." [6] - "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?" [6] - "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." [6] - "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" [6] - "Strategies for viral elimination should therefore be diversified across molecular targets and therapeutic modalities" [6] [1] SARS-CoV-2 infection rates of antibody-positive compared with antibody-negative health-care workers in England: a large, multicentre, prospective cohort study (SIREN) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040523/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040523/ [2] SARS-CoV-2 antibody-positivity protects against reinfection for at least seven months with 95% efficacy https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(21)00141-3/fulltext https://www.thelancet.com/journals/eclinm/article/PIIS2589-5... [3] Quantifying the risk of SARS‐CoV‐2 reinfection over time https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209951/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209951/ [4] Necessity of COVID-19 vaccination in previously infected individuals https://www.medrxiv.org/content/10.1101/2021.06.01.21258176v3 https://www.medrxiv.org/content/10.1101/2021.06.01.21258176v... [5] Distinct SARS-CoV-2 Antibody Responses Elicited by Natural Infection and mRNA Vaccination https://www.biorxiv.org/content/10.1101/2021.04.15.440089v4 https://www.biorxiv.org/content/10.1101/2021.04.15.440089v4 [6] 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/
mikem170 5y ago
This seems to be confirmed by data collected in Israel: [0] > More than 7,700 new cases of the virus have been detected during the most recent wave starting in May, but just 72 of the confirmed cases were reported in people who were known to have been infected previously – that is, less than 1% of the new cases. > Roughly 40% of new cases – or more than 3,000 patients – involved people who had been infected despite being vaccinated. They calculated that Israelis who were vaccinated were 6.72 times more likely to get infected after the shot than after natural infection. [0] https://www.israelnationalnews.com/News/News.aspx/309762 https://www.israelnationalnews.com/News/News.aspx/309762
- criticaltinker 5y ago
  This has been shared in other discussions on HN but no one has been able to find a peer-reviewed publication or official source supporting the data. Unless you can provide a reference to a primary source, your comment must be dismissed as misinformation.
  - kbelder 5y ago
    "Coronavirus patients who recovered from the virus were far less likely to become infected during the latest wave of the pandemic than people who were vaccinated against COVID, according to numbers presented to the Israeli Health Ministry." Nobody is making the claim it came from an academic journal. It was supposedly in data released by an Israeli government agency. Now, I don't know if that's true or not; but it's wrong to suggest anything that doesn't come from a peer-reviewed paper is misinformation.
    - criticaltinker 5y ago
      > it's wrong to suggest anything that doesn't come from a peer-reviewed paper is misinformation I agree with you - I updated my comment to be more clear in this regard. > It was supposedly in data released by an Israeli government agency Correct and no one has been able to find an official public source for this data. Unless someone can provide such a reference, I hope you agree that we must consider it misinformation.
ericb 5y ago
I wonder if a V2 of the vaccine with multiple independent targets is where we'll end up? Right now, covid is winning the math-war, with more mutation at-bats on average than it needs to hit a home run with its batting average. Say the chance of any one area of attack being evaded is 1%. If successful variant candidates must hit two simultaneous mutations, now it is 0.01%. Throw in a third at 0.0001%. At a certain point, it would seem like you can make the math unfavorable to the virus, especially if your targets are against these more optimized strains--in order to mutate, it might be stuck with less-optimized mutations to get off the local maxima. Anyone know the status of any multi-valent vaccines?
Veliladon 5y ago
Uhhh... They only used 10 people?

29 points by hudon 5y ago

It was clear from the start that SARS-CoV-2 would become endemic. Very interesting write up + data here. > Cure-Hub's data shows less antibody diversity in vaccinated individuals than naturally infected individuals. Fewer unique antibodies provide the virus with an avenue for immune escape through S protein mutations. The data compares natural immunity vs vaccinated immunity. I'm curious to see this data compared against individuals who were infected and were then vaccinated vs. individuals who were vaccinated then infected.

criticaltinker 5y ago
I have no primary sources to offer regarding this question. But here's some pure speculation if you're interested - assuming immunological memory operates in a 'most recently used' fashion, then it would follow that individuals will develop an immune response that trends toward being most effective at neutralizing the viral profile that was last seen. Consequently, the studies and data that evaluate natural immunity vs vaccinated immunity could be fairly applicable. In practice I'm sure you'd see a blending of the two immune responses, but timing of exposure could play a big factor in weighting that balance.

criticaltinker 5y ago

This blog post from Cure-Hub LLC is not a peer-reviewed primary source, but the claims made within do cite the literature fairly appropriately and accurately. Here I've outlined the most important claims, and where citations were provided, I included excerpts from the cited literature to support the claim. > "multiple studies show that reinfection in people with natural immunity is rare" - "A previous history of SARS-CoV-2 infection was associated with an 84% lower risk of infection, with median protective effect observed 7 months following primary infection. This study shows that previous infection with SARS-CoV-2 induces effective immunity to future infections in most individuals." [1] - "Reinfection is rare in the young and international population of Qatar. Natural infection appears to elicit strong protection against reinfection with an efficacy ~95% for at least seven months." [2] - "To our knowledge, this is the first systematic review to synthesise the evidence on the risk of SARS‐CoV‐2 reinfection over time. [...] Reinfection was an uncommon event (absolute rate 0%–1.1%), with no study reporting an increase in the risk of reinfection over time. [...] These data suggest that naturally acquired SARS‐CoV‐2 immunity does not wane for at least 10 months post‐infection. However, the applicability of these studies to new variants or to vaccine‐induced immunity remains uncertain." [3] - "Cumulative incidence of COVID-19 was examined among 52238 employees in an American healthcare system. COVID-19 did not occur in anyone over the five months of the study among 2579 individuals previously infected with COVID-19, including 1359 who did not take the vaccine. [...] Individuals who have had SARS-CoV-2 infection are unlikely to benefit from COVID-19 vaccination, and vaccines can be safely prioritized to those who have not been infected before." [4] > "Data also suggests that natural immunity is more protective than vaccine related immunity" > "The most significant difference between vaccinated and naturally infected individuals is the antibody response against nucleocapsid (N) protein" The author is basing this claim on the Cure-Hub data, but did not cite any literature on this. The finding is consistent with other papers, for example see [5]. - "The nucleocapsid protein (NP) is an immunodominant antigen for which the antibody response increases in concordance with natural exposure (Figure 2A,3A and 4)." [5] - "However, nucleocapsid is not a component of the mRNA vaccines and consequently there is no vaccine-induced increase in Ab against this antigen. Accordingly, anti-spike antibody levels increased in vaccinees while the nucleocapsid protein Ab level remained constant." [5] > "Cure-Hub's data shows less antibody diversity in vaccinated individuals than naturally infected individuals." > "Fewer unique antibodies provide the virus with an avenue for immune escape through S protein mutations." The author did not cite any literature on this claim either, so I'm providing an example here [6]. - "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." [6] - "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?" [6] - "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." [6] - "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" [6] - "Strategies for viral elimination should therefore be diversified across molecular targets and therapeutic modalities" [6] [1] SARS-CoV-2 infection rates of antibody-positive compared with antibody-negative health-care workers in England: a large, multicentre, prospective cohort study (SIREN) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040523/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040523/ [2] SARS-CoV-2 antibody-positivity protects against reinfection for at least seven months with 95% efficacy https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(21)00141-3/fulltext https://www.thelancet.com/journals/eclinm/article/PIIS2589-5... [3] Quantifying the risk of SARS‐CoV‐2 reinfection over time https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209951/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209951/ [4] Necessity of COVID-19 vaccination in previously infected individuals https://www.medrxiv.org/content/10.1101/2021.06.01.21258176v3 https://www.medrxiv.org/content/10.1101/2021.06.01.21258176v... [5] Distinct SARS-CoV-2 Antibody Responses Elicited by Natural Infection and mRNA Vaccination https://www.biorxiv.org/content/10.1101/2021.04.15.440089v4 https://www.biorxiv.org/content/10.1101/2021.04.15.440089v4 [6] 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/

mikem170 5y ago

This seems to be confirmed by data collected in Israel: [0] > More than 7,700 new cases of the virus have been detected during the most recent wave starting in May, but just 72 of the confirmed cases were reported in people who were known to have been infected previously – that is, less than 1% of the new cases. > Roughly 40% of new cases – or more than 3,000 patients – involved people who had been infected despite being vaccinated. They calculated that Israelis who were vaccinated were 6.72 times more likely to get infected after the shot than after natural infection. [0] https://www.israelnationalnews.com/News/News.aspx/309762 https://www.israelnationalnews.com/News/News.aspx/309762

criticaltinker 5y ago
This has been shared in other discussions on HN but no one has been able to find a peer-reviewed publication or official source supporting the data. Unless you can provide a reference to a primary source, your comment must be dismissed as misinformation.
- kbelder 5y ago
  "Coronavirus patients who recovered from the virus were far less likely to become infected during the latest wave of the pandemic than people who were vaccinated against COVID, according to numbers presented to the Israeli Health Ministry." Nobody is making the claim it came from an academic journal. It was supposedly in data released by an Israeli government agency. Now, I don't know if that's true or not; but it's wrong to suggest anything that doesn't come from a peer-reviewed paper is misinformation.
  - criticaltinker 5y ago
    > it's wrong to suggest anything that doesn't come from a peer-reviewed paper is misinformation I agree with you - I updated my comment to be more clear in this regard. > It was supposedly in data released by an Israeli government agency Correct and no one has been able to find an official public source for this data. Unless someone can provide such a reference, I hope you agree that we must consider it misinformation.

ericb 5y ago

I wonder if a V2 of the vaccine with multiple independent targets is where we'll end up? Right now, covid is winning the math-war, with more mutation at-bats on average than it needs to hit a home run with its batting average. Say the chance of any one area of attack being evaded is 1%. If successful variant candidates must hit two simultaneous mutations, now it is 0.01%. Throw in a third at 0.0001%. At a certain point, it would seem like you can make the math unfavorable to the virus, especially if your targets are against these more optimized strains--in order to mutate, it might be stuck with less-optimized mutations to get off the local maxima. Anyone know the status of any multi-valent vaccines?

Veliladon 5y ago

Uhhh... They only used 10 people?