3 ms·

A broader set of antibodies does not necessarily have to be beneficial. They might be targeting parts of the virus that could change without it losing its funct

A broader set of antibodies does not necessarily have to be beneficial. They might be targeting parts of the virus that could change without it losing its function. The spike protein seems to be close to indispensable for this virus. Targetting it specifically instead of just 'something', might therefore be the preferable thing.

anonuser123456 5y ago
Right, but it is harder for an organism to make multiple adaptations at once. Natural infection produces antibodies that target the spike protein as well as other sites. To evade immunity, the virus would need to change both sites. It is very clear that the vaccine is putting selective pressure on spike protein evolution. Having alternative targets makes it harder to escape. We currently don’t know if those other sites are beneficial or not. Sometimes they can even be counter productive (ADE, but we don’t really see that yet?)
- ithkuil 5y ago
  (genuine question) What does prevent us from creating mRNA vaccines that target multiple sites and not only the spike protein?
  - raphlinus 5y ago
    https://theconversation.com/covid-vaccines-focus-on-the-spike-protein-but-heres-another-target-150315 https://theconversation.com/covid-vaccines-focus-on-the-spik... is probably relevant to your question. The short answer (this was also discussed recently on TWiV) is that spike is the earliest interaction with cells, so focusing on it hopefully causes the immune response to mount earlier as well. But, as described in the link, other proteins may be viable targets as well.
    - anonuser123456 5y ago
      Another issue is, other targets may not provide neutralizing immunity and may facilitate ADE. I don't think we've seen ADE in natural infection yet, so it may just be a theoretical issue, but I also don't know if we've really looked for ADE in natural infection either. We do know that other similar coronavirus vaccine candidates (a candidate for SARS-COV-1) exhibited ADE in primate studies. So since the spike protein appears effective currently, maybe it's best to stick with that.
      - raphlinus 5y ago
        For people curious about ADE (a fascinating topic that so far doesn't seem to have caused problems with SARS-CoV-2), here is some excellent background reading that covers many of the points made in the above comment, with citations and deeper discussion: https://blogs.sciencemag.org/pipeline/archives/2021/02/12/antibody-dependent-enhancement-and-the-coronavirus-vaccines https://blogs.sciencemag.org/pipeline/archives/2021/02/12/an...
        anonuser123456 5y ago
        I remember when this whole thing originally broke out, ADE was my biggest fear. Even when China was talking about a 2-3% infection fatality rate, it's like ok.. well that's not going to shatter society. But ADE... the prospect that getting it a 2nd time would raise the IFR to who knows... 20+%? That was scary.

anonuser123456 5y ago

Right, but it is harder for an organism to make multiple adaptations at once. Natural infection produces antibodies that target the spike protein as well as other sites. To evade immunity, the virus would need to change both sites. It is very clear that the vaccine is putting selective pressure on spike protein evolution. Having alternative targets makes it harder to escape. We currently don’t know if those other sites are beneficial or not. Sometimes they can even be counter productive (ADE, but we don’t really see that yet?)

ithkuil 5y ago
(genuine question) What does prevent us from creating mRNA vaccines that target multiple sites and not only the spike protein?
- raphlinus 5y ago
  https://theconversation.com/covid-vaccines-focus-on-the-spike-protein-but-heres-another-target-150315 https://theconversation.com/covid-vaccines-focus-on-the-spik... is probably relevant to your question. The short answer (this was also discussed recently on TWiV) is that spike is the earliest interaction with cells, so focusing on it hopefully causes the immune response to mount earlier as well. But, as described in the link, other proteins may be viable targets as well.
  - anonuser123456 5y ago
    Another issue is, other targets may not provide neutralizing immunity and may facilitate ADE. I don't think we've seen ADE in natural infection yet, so it may just be a theoretical issue, but I also don't know if we've really looked for ADE in natural infection either. We do know that other similar coronavirus vaccine candidates (a candidate for SARS-COV-1) exhibited ADE in primate studies. So since the spike protein appears effective currently, maybe it's best to stick with that.
    - raphlinus 5y ago
      For people curious about ADE (a fascinating topic that so far doesn't seem to have caused problems with SARS-CoV-2), here is some excellent background reading that covers many of the points made in the above comment, with citations and deeper discussion: https://blogs.sciencemag.org/pipeline/archives/2021/02/12/antibody-dependent-enhancement-and-the-coronavirus-vaccines https://blogs.sciencemag.org/pipeline/archives/2021/02/12/an...
      - anonuser123456 5y ago
        I remember when this whole thing originally broke out, ADE was my biggest fear. Even when China was talking about a 2-3% infection fatality rate, it's like ok.. well that's not going to shatter society. But ADE... the prospect that getting it a 2nd time would raise the IFR to who knows... 20+%? That was scary.