7 ms·

I thought it was sort of the other way around; that your immune system is keying into some fairly random and subjective set of dna features on the specific vira

I thought it was sort of the other way around; that your immune system is keying into some fairly random and subjective set of dna features on the specific viral strain you've been infected with. But that with the mRNA vaccines, your body is being explicitly taught about the spike protein, nothing more, nothing less. So provided any future infection employs a spike protein, you have immunity. The question is, what are the odds that sars-cov2 would evolve an entirely different mechanism from the spike protein? My impression was that's pretty unlikely, and why there's so much confidence the mRNA vaccines are robust against variants. I know absolutely nothing about this subject and frankly am unqualified to even participate in this discussion. I'm just hoping someone who is can clarify/correct my understanding if it's totally misinformed.

vmception 5y ago
Its unlikely to evolve an infection mechanism besides the spike protein. There will be plenty of mutant evolutionary deadends that live and die in a few days.
hanklazard 5y ago
Based on work from similar coronaviruses, the spike protein was quickly identified at the beginning of the pandemic as an important component for viral binding to the ACE-2 receptor. It is one protein component of the viral shell, but has proven to be an excellent target, given its induced immune response to the mRNA vaccines. Covid will not be able to mutate away from using the spike protein, but it will continue to evolve mutations within the protein as it responds to selective pressure. Fortunately, when the body creates an adaptive immune response through antibody or the T-cell receptor, this response is polyclonal. Think of it as not a single antibody to spike but rather a population of antibodies, all targeting a variety of residues on the protein. This is why most immunologists are not terribly worried about the variants that have emerged wrecking all of our immunization efforts—those variants are usually based on just a couple of mutant residues and so will not (generally speaking) be able to evade the population of antibody and t-cell responses that have been generated. You may have heard about monoclonal antibody therapies to covid ... those, unfortunately, are very susceptible to mutation because if a critical targeted residue mutates, you could lose all efficacy of the drug. The only answer to rapidly mutating pathogens is an entire inducible population of neutralizing proteins in each of us and it’s no coincidence that we have this defense. If we didn’t, our species could not be here right now.
- Scoundreller 5y ago
  > You may have heard about monoclonal antibody therapies to covid ... those, unfortunately, are very susceptible to mutation because if a critical targeted residue mutates, you could lose all efficacy of the drug. Depends if the therapy works on the virus itself, or your body's response to the infection. I think most of the monoclonal antibodies are working on your body's (over)response, so mutations shouldn't change much. Same with corticosteroids. But Nucloside/tide analogues on the other hand or anything else working against viral processes/replication, oh yeah.
  - hanklazard 5y ago
    I should have been more clear about the monoclonals I was referring to, which are those targeting the virus itself (1). You may be thinking of the targeted immune modulators against inflammatory cytokines like TNF-alpha (2) and IL-6 (3). Some of those are antibodies, others are pieces of antibody fused to other proteins. Regardless, those types of treatments would not be affected directly by viral mutation, whereas the first type I described above have already been shown to be less effective with existing mutations (4). 1. https://en.m.wikipedia.org/wiki/Casirivimab/imdevimab https://en.m.wikipedia.org/wiki/Casirivimab/imdevimab 2. https://en.m.wikipedia.org/wiki/Casirivimab/imdevimab https://en.m.wikipedia.org/wiki/Casirivimab/imdevimab 3. https://www.covid19treatmentguidelines.nih.gov/immunomodulators/interleukin-6-inhibitors/ https://www.covid19treatmentguidelines.nih.gov/immunomodulat... 4. https://science.sciencemag.org/content/371/6531/850 https://science.sciencemag.org/content/371/6531/850

vmception 5y ago

Its unlikely to evolve an infection mechanism besides the spike protein. There will be plenty of mutant evolutionary deadends that live and die in a few days.

hanklazard 5y ago

Based on work from similar coronaviruses, the spike protein was quickly identified at the beginning of the pandemic as an important component for viral binding to the ACE-2 receptor. It is one protein component of the viral shell, but has proven to be an excellent target, given its induced immune response to the mRNA vaccines. Covid will not be able to mutate away from using the spike protein, but it will continue to evolve mutations within the protein as it responds to selective pressure. Fortunately, when the body creates an adaptive immune response through antibody or the T-cell receptor, this response is polyclonal. Think of it as not a single antibody to spike but rather a population of antibodies, all targeting a variety of residues on the protein. This is why most immunologists are not terribly worried about the variants that have emerged wrecking all of our immunization efforts—those variants are usually based on just a couple of mutant residues and so will not (generally speaking) be able to evade the population of antibody and t-cell responses that have been generated. You may have heard about monoclonal antibody therapies to covid ... those, unfortunately, are very susceptible to mutation because if a critical targeted residue mutates, you could lose all efficacy of the drug. The only answer to rapidly mutating pathogens is an entire inducible population of neutralizing proteins in each of us and it’s no coincidence that we have this defense. If we didn’t, our species could not be here right now.

Scoundreller 5y ago
> You may have heard about monoclonal antibody therapies to covid ... those, unfortunately, are very susceptible to mutation because if a critical targeted residue mutates, you could lose all efficacy of the drug. Depends if the therapy works on the virus itself, or your body's response to the infection. I think most of the monoclonal antibodies are working on your body's (over)response, so mutations shouldn't change much. Same with corticosteroids. But Nucloside/tide analogues on the other hand or anything else working against viral processes/replication, oh yeah.
- hanklazard 5y ago
  I should have been more clear about the monoclonals I was referring to, which are those targeting the virus itself (1). You may be thinking of the targeted immune modulators against inflammatory cytokines like TNF-alpha (2) and IL-6 (3). Some of those are antibodies, others are pieces of antibody fused to other proteins. Regardless, those types of treatments would not be affected directly by viral mutation, whereas the first type I described above have already been shown to be less effective with existing mutations (4). 1. https://en.m.wikipedia.org/wiki/Casirivimab/imdevimab https://en.m.wikipedia.org/wiki/Casirivimab/imdevimab 2. https://en.m.wikipedia.org/wiki/Casirivimab/imdevimab https://en.m.wikipedia.org/wiki/Casirivimab/imdevimab 3. https://www.covid19treatmentguidelines.nih.gov/immunomodulators/interleukin-6-inhibitors/ https://www.covid19treatmentguidelines.nih.gov/immunomodulat... 4. https://science.sciencemag.org/content/371/6531/850 https://science.sciencemag.org/content/371/6531/850