Pfizer vaccine: can it handle new variants?

How concerned should we be about new coronavirus variants? The evidence is still coming in. They all seem to spread faster, and there are hints that a couple may possibly be more lethal, or make serious illness more common. The real question, though, is whether vaccines still work against them. That’s what University of Texas biologist Pei-Yong Shi is trying to answer - as he told Phil Sansom...

Pei-Yong - Based on all the data so far we've accumulated, we think that, at this point, the vaccine still works quite well against the mutant viruses we've tested so far.

Phil - That's a relief...

Pei-Yong - Yes. Using what we call the reverse genetic system, you can make the virus, and then manipulate it at any position you want; and then through animal models and the cells, we can really look at their properties.

Phil - Pei-Yong’s team pioneered this “reverse genetic system”, a method for rapidly generating viruses with exactly the mutations you want to study. They’ve partnered with Pfizer and are receiving samples of blood from people who got the Pfizer vaccine. They then test the blood on their engineered viruses to see if the immune response still works. The first thing they’re comparing is individual mutations rather than the combinations of them you get in these variants.

Pei-Yong - There are prominent mutations such as the 501Y mutation. And that mutation is very particular because it's not only recovered from the UK variants, but also it was recovered from the South African strain and the Brazilian strain. And what we found is that mutation doesn't seem to affect the inhibition of the viruses by the immunised blood.

Phil - Basically no difference with this new mutation.

Pei-Yong - Yeah, very, very minor differences, yeah. If there is any.

Phil - That’s a relief, because N501Y is one of two crucial mutations found in the bit of the coronavirus that binds to human cells. The name is referring to amino acids, which are the building blocks of proteins that the genes are coding for. Here, thanks to the mutation, amino acid number 501 has changed from a type called N to a type called Y. Pei-Yong has also tested the second of the two crucial mutations.

Pei-Yong - In the South Africa strain there is this mutation '484'. And this change has been well documented before: that once you have this change, the virus will reduce its sensitivity to monoclonal antibodies. And that is a very worrisome mutation. In order to study that, we did a similar kind of trick. We do see it very modestly reduces the inhibition activities of the blood; but this reduction decrease is very minor and modest.

Phil - Right, so in combination, how much are they reducing the vaccine's power by?

Pei-Yong - In the South African strain, you can consistently see there are seven mutations or deletions. Just now we're just talking about one by one. The question is, if you put them all together, what is the total effect? That is still ongoing; maybe next week we'll get all the answers to that. Which what we did is: we made a virus that has all those seven mutations, and then we are now testing how that is going to affect the total inhibition by the vaccinated blood.

Phil - Wow, this is a quite a big job, isn't it? Because there's a bunch of variants out now. Do you have to test all of them?

Pei-Yong - Well, that's what keeps us very, very... whether they add together or they are counteractive... this the only way we'll be able to get to the bottom of these functions.

Phil - And then do you have to test each version against each type of vaccine as well?

Pei-Yong - I would think the results can be generalised to the different vaccine platforms, because they're all encoding the same sequence of the spike protein. But at the same time, we should be very cautious.

Phil - And then what's the point where you see something that makes you go, "oh boy, time for a new vaccine"?

Pei-Yong - Before we can reach that consensus or decision, there are still a lot of questions we don't know. For example, what is the minimum antibody level that is required to protect us from being infected? That minimum bar, that number, has not been defined at all. And this is a very, very important number. Let's say after people get vaccinated by Pfizer's vaccine, they have an average antibody level of '600'. Now let's say with the new variants, 600 becomes 200. 200, I think, is still way above the minimum requirement to get us protected. So there is a misconception: if the antibody level is reduced by threefold, that doesn't mean the efficacy is going to drop by threefold. But unfortunately right now don't know what is the minimum bar required.

Since recording Pei-Yong Shi has reported in the New England Journal of Medicine the work testing the full combination of mutations in the crucial part of variant B.1.351, the variant from South Africa. Pfizer’s vaccine works only a third as well against it compared to other variants.