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Since there are probably specialists out there, can you answer me a question? Since these vaccines are targeting spike proteins, shouldn't they work with every

Since there are probably specialists out there, can you answer me a question? Since these vaccines are targeting spike proteins, shouldn't they work with every variant? Is there (big) risk of a mutation actually changing the spike protein?

raphlinus 6y ago
I'm not a specialist, but I can link you to the answer: [1] Key quote: "B.1.1.7 is defined by 23 mutations from the original Wuhan strain, 8 of which are in the spike protein. The 3 mutations hypothesized to have the largest potential biological effect are N501Y, spike deletion 69-70del and P681H." The B.1.351 (South Africa) variant has N501Y but not the 69-70 deletion. We're still learning, but virologists I follow are concerned that N501Y may be a driver of higher transmission. But it's likely that multiple mutations contribute. [1]: https://asm.org/Articles/2021/January/B-1-1-7-What-We-Know-About-the-Novel-SARS-CoV-2-Va https://asm.org/Articles/2021/January/B-1-1-7-What-We-Know-A...
thehappypm 6y ago
When the immune system creates antibodies, they basically hug the spike protein and build antibodies on every nook and cranny they can find a way to bind an antibody. These regions are called epitopes, and the immune system creates many antibodies for each invader. If the spike protein mutates, it means that the structure of the spike is different. Obviously the spike can't change too much, because it needs to still be able to latch onto cells, and many changes would be irrelevant. Even if one antibody suddenly stops working because of a slight shift in the protein, there are other antibodies targeting different parts of the protein that would still be effective. Only if the spike changes so dramatically that literally none of the antibodies you had before are relevant anymore. That's why it's not super expected that we'll get a version of the virus that these vaccines won't at least produce some antibodies against.
- traveler01 6y ago
  Thank you. Basically they could just change the actual vaccine a bit to cover all those variants right?
CyanLite2 6y ago
ELI5: The spike protein itself is changing on the virus.
sjg007 6y ago
Yes there is a big risk that the vaccines won't work if the viral spike protein has sufficiently diverged from the one encoded by the vaccine's mRNA template. Viral proteins are constantly changing. They accumulate sequence mutations both naturally and due to selective pressure. There's a limited landscape of acceptable changes but we don't know what those are and how they relate to each other. All we can do is generate new mRNA templates to the more popular strains and revaccinate. This means that we will most likely we will end up taking a cocktail of mRNA vaccines and yearly boosters.. with new mRNA templates. "Won't work" in this case is defined on a spectrum. Moderna's vaccine is currently about 90% efficacious. Newer variants could reduce that down to say 60% or more. At some point the current vaccine could become useless.
- traveler01 6y ago
  But could they become useless before we "solve" this pandemic? Is actually my fear and other "noobs" in this matters.
  - sjg007 6y ago
    yep.

raphlinus 6y ago

I'm not a specialist, but I can link you to the answer: [1] Key quote: "B.1.1.7 is defined by 23 mutations from the original Wuhan strain, 8 of which are in the spike protein. The 3 mutations hypothesized to have the largest potential biological effect are N501Y, spike deletion 69-70del and P681H." The B.1.351 (South Africa) variant has N501Y but not the 69-70 deletion. We're still learning, but virologists I follow are concerned that N501Y may be a driver of higher transmission. But it's likely that multiple mutations contribute. [1]: https://asm.org/Articles/2021/January/B-1-1-7-What-We-Know-About-the-Novel-SARS-CoV-2-Va https://asm.org/Articles/2021/January/B-1-1-7-What-We-Know-A...

thehappypm 6y ago

When the immune system creates antibodies, they basically hug the spike protein and build antibodies on every nook and cranny they can find a way to bind an antibody. These regions are called epitopes, and the immune system creates many antibodies for each invader. If the spike protein mutates, it means that the structure of the spike is different. Obviously the spike can't change too much, because it needs to still be able to latch onto cells, and many changes would be irrelevant. Even if one antibody suddenly stops working because of a slight shift in the protein, there are other antibodies targeting different parts of the protein that would still be effective. Only if the spike changes so dramatically that literally none of the antibodies you had before are relevant anymore. That's why it's not super expected that we'll get a version of the virus that these vaccines won't at least produce some antibodies against.

traveler01 6y ago
Thank you. Basically they could just change the actual vaccine a bit to cover all those variants right?

CyanLite2 6y ago

ELI5: The spike protein itself is changing on the virus.

sjg007 6y ago

Yes there is a big risk that the vaccines won't work if the viral spike protein has sufficiently diverged from the one encoded by the vaccine's mRNA template. Viral proteins are constantly changing. They accumulate sequence mutations both naturally and due to selective pressure. There's a limited landscape of acceptable changes but we don't know what those are and how they relate to each other. All we can do is generate new mRNA templates to the more popular strains and revaccinate. This means that we will most likely we will end up taking a cocktail of mRNA vaccines and yearly boosters.. with new mRNA templates. "Won't work" in this case is defined on a spectrum. Moderna's vaccine is currently about 90% efficacious. Newer variants could reduce that down to say 60% or more. At some point the current vaccine could become useless.

traveler01 6y ago
But could they become useless before we "solve" this pandemic? Is actually my fear and other "noobs" in this matters.
- sjg007 6y ago
  yep.