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rosyatrandom10

It might be useful to draw up the happy pathway to developing mRNA vaccines against spike proteins, and examining all the issues along the way.

My (very limited). understanding:

  • Coronaviruses use spike proteins to enter target cells
  • The immune system can
    • learn to recognise these proteins as foreign, then
    • generate a response when it encounters them
  • mRNA vaccines can
    • cause host tissue to display identified spike proteins
    • initiate the same immune response mechanism above
  • Mutations to spike proteins can
    • occasionally increase/not-decrease virus fitness (transmissibility etc.)
    • evade existing immune responses as they are no longer recognised

So, what are the issues that prevent

  1. strain with distinct spike proteins identified
  2. mRNA vaccine altered to display new spike proteins and initiate immune recognition

Is it

  • identifying the new spike proteins
  • replicating them via mRNA with enough fidelity
  • getting the host cells to display them
  • getting the host immune system to identify them as foreign
  • getting the host immune system to mount a sufficient response
  • preventing false positives from arising, with the immune system targeting incorrect entities

Or other things?

On the face of it, it seems almost like a trivial problem... but this is biology, so of course it isn't.

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by ChristianKl
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Delta and Delta Plus evade the antibody response:

Delta and Delta Plus were less well inhibited (neutralized) by antibodies from infected and vaccinated individuals as compared to the original virus and this likely contributed to the rapid spread of Delta.

It seems to me relatively straightforward that if we would update the vaccine to the spike protein of the delta varient that would help with protecting against it. When talking to people on Facebook I heared strange arguments such as the "vaccine working well" against delta with seems like a really bogus statement given the need for booster shots and many vaccinated spreading the virus. Yes, the vaccine helps but that's no reason not to update it to make it help more. 

Can anyone make sense of this?

Covid-19
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Why don't our vaccines get updated to the delta spike protein?
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evhub

00

One major reason may be because it wouldn't actually be very effective to do so due to original antigenic sin. See my comment here.

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[-]jimv60

It looks like for Omicron at least Modena, and possibly Pfizer too, will be working on vaccine updates, according to tweets:

https://mobile.twitter.com/moderna_tx/status/1464332834211045380

https://mobile.twitter.com/andrew_croxford/status/1464251996630831109

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[-]rosyatrandom10

It might be useful to draw up the happy pathway to developing mRNA vaccines against spike proteins, and examining all the issues along the way.

My (very limited). understanding:

  • Coronaviruses use spike proteins to enter target cells
  • The immune system can
    • learn to recognise these proteins as foreign, then
    • generate a response when it encounters them
  • mRNA vaccines can
    • cause host tissue to display identified spike proteins
    • initiate the same immune response mechanism above
  • Mutations to spike proteins can
    • occasionally increase/not-decrease virus fitness (transmissibility etc.)
    • evade existing immune responses as they are no longer recognised

So, what are the issues that prevent

  1. strain with distinct spike proteins identified
  2. mRNA vaccine altered to display new spike proteins and initiate immune recognition

Is it

  • identifying the new spike proteins
  • replicating them via mRNA with enough fidelity
  • getting the host cells to display them
  • getting the host immune system to identify them as foreign
  • getting the host immune system to mount a sufficient response
  • preventing false positives from arising, with the immune system targeting incorrect entities

Or other things?

On the face of it, it seems almost like a trivial problem... but this is biology, so of course it isn't.

Reply
[-]Yair Halberstadt10

Given that

  1. Developing a new version of the vaccine would probably face significant regulatory hurdle, and thus take time.
  2. There's an expectation for new variants to become dominant every few months.
  3. The vaccine industry is either way going to sell as many vaccines as it can produce for the foreseeable future.

There doesn't seem to be a huge incentive for vaccine companies to go through the pain and expense of developing a new vaccine version, which would only be useful for a few months, and which just displaces sales from its existing vaccine instead of creating new sales.

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[-]ChristianKl*40

Developing a new version of the vaccine would probably face significant regulatory hurdle, and thus take time.

According to Pfizer, it should take 100 days. If they would have started that when it become clear that Delta will be soon the prevailing variant, we would have had access to the updated vaccine for a few months.

There's an expectation for new variants to become dominant every few months.

The best prediction seems to be those new variants will be varients of what's currently the most common variant and thus a vaccine that's updated against delta will be nearer to new variants.

The vaccine industry is either way going to sell as many vaccines as it can produce for the foreseeable future.

That's an argument why the companies don't want to do it on their own but not one for the lack of political pressure on them. It would be one of the main things a politician like Biden could do to actually fight the pandemic if that would be a political priority.

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[-]Max Hoyer20
  1. might be true, but about the other points:
  2. I'm not an immunologist, but if new variants develop from the last new dominant strain (i.e. a new dominant strain would evolve from delta as a start-off point), would that not still give a delta-specific vaccine an edge against future variants as compared to the original vaccines?
  3. This argument doesn't really track for me. The vaccine industry is not a monolith and normal market competition should provide plenty incentives to produce a better vaccine than your competitors. Not to mention that the researchers and executives there likely have other motives than pure profit as well.
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[-]Jonathan_Graehl20

Trying to push out a revision costs money and doesn't earn any expected money. And everyone knows this is so. Unofficial market collusion regularly manages to solve harder problems; you don't need explicit comms at all.

I'll grant that we'll hear some competitive "ours works better on variant X" marketing but a new even faster approval track would be needed if we really wanted rapid protein updates.

As evhub mentions, the antibodies you make given the first vaccine you're exposed to are what will get manufactured every time you see a similar-enough provocation. It may be impossible to switch the learned immune response without some specially designed "different enough" protein that's hoped to also be protective against the latest variant. I buy the 'original antigenic sin' concept - there has to be a reason we're not naturally immune to flu and corona-colds already after many previous encounters.

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