5 ms·

For the vaccine to lose effectiveness, the mutation would have to drastically alter the spike protein of the virus. This is effectively impossible as the virus

For the vaccine to lose effectiveness, the mutation would have to drastically alter the spike protein of the virus. This is effectively impossible as the virus is dependent on a functioning spike protein in order to infect cells, and the machinery involved with the mechanics of the spike are extremely delicate. Errant mutations that would cause compositional changes to the shape of the protein are almost guaranteed to cause functional failure. Using terminology, this is what we call a highly conserved area. In both cases for the South African or UK strain, if you take a look at the areas where mutations have occurred, you’ll see that the code responsible for generating the spike protein is basically completely unaffected. This will generally hold true for any successive future strains.

enchiridion 6y ago
While that may be true, I think that scale plays a role here. The ancestors of this virus were bouncing around between a relatively small set of humans and animals for a while before becoming SARS-CoV-2. Now with a significant portion of the world infected, it does not seem unreasonable that it would mutate. Although at that point it probably would not be considered the same virus anymore.
deleted 6y ago
[deleted]
hn_throwaway_99 6y ago
This doesn't make much sense to me, given that coronaviruses, with spike proteins, have existed for eons, and humans have had lots of time to build up immunity to previous coronaviruses (ones that cause colds, for example). So there was something about the Covid-19 coronavirus spike proteins that was different enough where it didn't look like "familiar" coronaviruses, so I see no reason why it couldn't evolve further to evade whatever antibodies humans are able to build up to the vaccines.
- sudosysgen 6y ago
  You can make multiple spike proteins that target the same receptor. This generally happens when a virus from another animal (and thus with a slightly different version of the receptor) adapts to humans. Basically, a gradient descent from a very different starting point ending up in a different local minima. The question is, is the spike protein at a local minima (very probably quite close to it), and could it jump to another local minima then? Most likely not. It's possible it will evolve to make our antibodies slightly less effective, likely as a trade off for infectiousness, but incredibly unlikely the spike protein would evolve to be unrecognizable to our immune systems. Historically, this doesn't happen all that often, except for viruses with chronic infections over years that can do a deeper search over the gradient, but even then it generally takes years to decades.
  - dimgl 6y ago
    This is extremely interesting. Thanks for this context. Detailed and thoughtful explanations like this help to understand the news.
  - lawrenceyan 6y ago
    Given the non-linear dynamics that proteins must live under, I like the usage of local minima as an analogy. It feels apt. Generally though, within the context of machine learning, one of the benefits of gradient descent, especially when stochastic, is that we can get past those local minima humps. Does this hold less true with respect to the process of sequence mutation that viruses go through?
    - sudosysgen 6y ago
      The difference in viruses is that if you get on the hump, you are outcompeted by other viruses that stayed in the minimum, which makes it a lot more difficult.
      - lawrenceyan 6y ago
        That makes a lot of sense. Thanks!
alevskaya 6y ago
This isn't correct. The constraints placed upon epitopes by the cell receptor vs antibodies aren't the same. Rhinoviruses and Influenza viruses escape past immunity without fundamentally altering their biology all the time! The 2nd paper cited does in fact show functional virus with a charge-shifting E->K mutation in its receptor binding domain that escape many antibodies raised against earlier strains. I used to engineer viruses and human immune cells for a living - maybe read a little more virology/immunology.
rolph 6y ago
you are speaking about a general case scenario, there is conservation of sequence region and variation of sequence region. to wit one protien encoding sequence has separate regions corresponding to regions of the product protien, the receptor binding domain[RBD] is a moderately conserved region ; the ImmunoAntigenic regions are not tightly linked to the protiens receptor binding function thus may vary at a greater rate than the RBD regions

enchiridion 6y ago

While that may be true, I think that scale plays a role here. The ancestors of this virus were bouncing around between a relatively small set of humans and animals for a while before becoming SARS-CoV-2. Now with a significant portion of the world infected, it does not seem unreasonable that it would mutate. Although at that point it probably would not be considered the same virus anymore.

deleted 6y ago

[deleted]

hn_throwaway_99 6y ago

This doesn't make much sense to me, given that coronaviruses, with spike proteins, have existed for eons, and humans have had lots of time to build up immunity to previous coronaviruses (ones that cause colds, for example). So there was something about the Covid-19 coronavirus spike proteins that was different enough where it didn't look like "familiar" coronaviruses, so I see no reason why it couldn't evolve further to evade whatever antibodies humans are able to build up to the vaccines.

sudosysgen 6y ago
You can make multiple spike proteins that target the same receptor. This generally happens when a virus from another animal (and thus with a slightly different version of the receptor) adapts to humans. Basically, a gradient descent from a very different starting point ending up in a different local minima. The question is, is the spike protein at a local minima (very probably quite close to it), and could it jump to another local minima then? Most likely not. It's possible it will evolve to make our antibodies slightly less effective, likely as a trade off for infectiousness, but incredibly unlikely the spike protein would evolve to be unrecognizable to our immune systems. Historically, this doesn't happen all that often, except for viruses with chronic infections over years that can do a deeper search over the gradient, but even then it generally takes years to decades.
- dimgl 6y ago
  This is extremely interesting. Thanks for this context. Detailed and thoughtful explanations like this help to understand the news.
- lawrenceyan 6y ago
  Given the non-linear dynamics that proteins must live under, I like the usage of local minima as an analogy. It feels apt. Generally though, within the context of machine learning, one of the benefits of gradient descent, especially when stochastic, is that we can get past those local minima humps. Does this hold less true with respect to the process of sequence mutation that viruses go through?
  - sudosysgen 6y ago
    The difference in viruses is that if you get on the hump, you are outcompeted by other viruses that stayed in the minimum, which makes it a lot more difficult.
    - lawrenceyan 6y ago
      That makes a lot of sense. Thanks!

alevskaya 6y ago

This isn't correct. The constraints placed upon epitopes by the cell receptor vs antibodies aren't the same. Rhinoviruses and Influenza viruses escape past immunity without fundamentally altering their biology all the time! The 2nd paper cited does in fact show functional virus with a charge-shifting E->K mutation in its receptor binding domain that escape many antibodies raised against earlier strains. I used to engineer viruses and human immune cells for a living - maybe read a little more virology/immunology.

rolph 6y ago

you are speaking about a general case scenario, there is conservation of sequence region and variation of sequence region. to wit one protien encoding sequence has separate regions corresponding to regions of the product protien, the receptor binding domain[RBD] is a moderately conserved region ; the ImmunoAntigenic regions are not tightly linked to the protiens receptor binding function thus may vary at a greater rate than the RBD regions