Thread by @kakape

Getting a lot of questions about vaccines and variants and why @moderna_tx is developing a booster based on variant discovered in South Africa if vaccines are thought to protect against it.
So a quick thread.
And story is up here:
sciencemag.org/news/2021/01/v…

@moderna_tx First of all, there are several ways in which new variants can worsen the situation:
They can be deadlier, more transmissible or more likely to infect people who have been infected already or received vaccines - or, of course, a combination of these.

@moderna_tx The biggest problem for the world RIGHT NOW are variants with increased transmissibility, because that means measures have to be stricter for the virus not to spread and if it does spread it means more disease and death before the world is vaccinated.

@moderna_tx But variants better able to escape immunity are important too and it is important here to distinguish between the situation now and what it means for the future.

@moderna_tx Right now, we have data showing that the virus has escaped immunity from some monoclonal antibodies.
This is not surprising: a monoclonal antibody is like that opponent in chess who always makes the same move.
It is easy to adapt to.

@moderna_tx This new preprint by David Ho’s group shows that 501Y.V2 already "is resistant to a major group of potent mAbs ..., including two authorized for emergency use”.
biorxiv.org/content/10.110…
As @JeremyFarrar told me: “We shouldn't be using single monoclonals."

@moderna_tx @JeremyFarrar The immunity humans develop from vaccines or infection is different: It consists of many different antibodies (polyclonal) and on top of that there are T cells.
So what is the picture, right now? I won’t go through it all, since @florian_krammer did so:

https://twitter.com/florian_krammer/status/1353900984209182720

@moderna_tx @JeremyFarrar @florian_krammer Short version: Evidence is accumulating that our antibodies are not as good at neutralising the South African variant as previous versions of the virus. Apart from Ho’s paper and the one by Moderna, there is a lot of work from South Africa, including this: medrxiv.org/content/10.110…

@moderna_tx @JeremyFarrar @florian_krammer But: The mRNA vaccines induce such high levels of antibodies that the drop may not matter much.
As @trvrb told me: "Given the high starting point, it’s conceivable [vaccine efficacy] could drop only slightly."

@moderna_tx @JeremyFarrar @florian_krammer @trvrb It’s important to remember that immunity is not black-and-white. For most people the drop in antibody neutralization may not matter, but for some on the margins it could push them into non-protected territory. Or the immunity could wane a little bit faster. We don’t know.

@moderna_tx @JeremyFarrar @florian_krammer @trvrb The other thing we don’t know: How will the virus evolve in the future?
For now the immune escape of the new variants seems to be mainly down to one mutation: E484K (again, read Ho’s paper).
“E484K is really the bad boy here,” @stgoldst told me.

@moderna_tx @JeremyFarrar @florian_krammer @trvrb @stgoldst The P.1 variant (spreading in Manaus) carries the same E484K mutation. Is that because the virus does not have that many ways to escape antibodies? Or does it have a lot of tricks and nasty surprises left? We just don’t know.

@moderna_tx @JeremyFarrar @florian_krammer @trvrb @stgoldst That is why preparing for variants that are even better at evading immunity is the right thing to do RIGHT NOW.
Moderna working on a third shot that could boost antibody levels is a good start because it will undoubtedly teach the company a lot about how that strategy works.

@moderna_tx @JeremyFarrar @florian_krammer @trvrb @stgoldst But it’s not just science, but also questions of regulatory approval, production etc. As @angie_rasmussen told me: "It’s also wise to begin thinking about how they will be distributed." For example: Will they be allocated to regions where the escape variants are circulating?

@moderna_tx @JeremyFarrar @florian_krammer @trvrb @stgoldst So all of this to say: When you see news of companies, regulators etc. working already on updating the vaccines, don’t let that scare you.
You should feel relieved!
For now, the vaccines are working and these efforts helps ensure they keep working!
sciencemag.org/news/2021/01/v…