Thread by @LauringLab

With the news of this new variant and discussions of what it means for vaccines, keep thinking about this article from @SCOTTeHENSLEY and Yewdell (who very much needs a Twitter account). Short thread.

science.sciencemag.org/content/326/59…

First question from ID docs and many virologists I know is “OMG, what does this mean for vaccines.” We grow up in this pathogen vs. immune system paradigm that is sometimes distracting from issues at play. (2)

Many variants have been reported to escape this serum or that monoclonal. But large scale selection of a variant at this point is probably not driven by immune system (just not that much immunity around). (3)

If a variant becomes more transmissible on the other hand, there’s a big payoff as it can spread quickly and dominate other variants. IMO this is why new variant is more concerning. Unlike D614G which arose when there wasn’t as much competition (founder effects) (4)

This one arose and took over from a lot of other variants that were already around. Suggests it is doing something better than the rest. Again, I do not think this has to do with immune escape and does not immediately suggest issues with vaccine. (5)

Which gets us back to spike, the protein that mediates attachment to cells and is also a major target of antibodies that neutralize the virus. If a mutation in spike makes the virus better at attaching to or getting in to cells, one can say variant might be more transmissible (6)

Now, those mutations *may* also make the virus less sensitive to antibody neutralization. But it's not nec antibody escape that is driving the variant. The Hensley paper gets at this a bit. And one needs to be careful. Testing with a few sera might not give the whole picture (7).

Viral glycoproteins like spike (and influenza HA) are also subject to trade-offs - cue eye roll from people who hear me talk about this a lot. A mutation that makes the virus better at one thing (binding to receptor) can sometimes make it worse at doing another (escaping Ab). (8)

So, it is entirely possible that mutations in spike that are *good* for virus right now, could also make it less fit in the face of large-scale immune pressure in the future. It's hard, but we can't get over the tips of our skis here. (9)

Unfortunately, we're going to have to wait to learn how this plays out . Sit tight. This variant could have implications for vaccines, but it could go either way. I'm way more concerned about its spread right now than what are at this point hypothetical impacts on vaccines. (10)