November 24, 2020

Like you, every Monday, I wake up giddy with excitement to discover which vaccine candidate has announced interim results. Will it be Novavax this week? Imperial? Which door in my little vaccine-candidate calendar will I get to open? Will there be a little lipid nanoparticle full of lengths of mRNA behind it? Or a modified chimpanzee adenovirus? It’s so exciting!

This week, of course, it was the Oxford/AstraZeneca vaccine, one week after Moderna announced their results and two weeks after Pfizer’s

The headline efficacy results of the Oxford trial are lower than for the other two vaccines. But it’s still great news, and it may be the case that the headline result is not the thing we ought to be looking at. And, most important, the Oxford vaccine, compared to the other two, can be made in far larger quantities far more quickly, can be stored and distributed much more easily, and will be available at a fraction of the cost.

The team is submitting its data to a journal probably around the time you read this, and it will be in the public domain in a week or so. At the moment we have no real data to look at — and, in fact, even the scientists who worked on it have not had access to all of it. So I thought it might be useful to try to collate what we can know, so far.

First, that headline result. The Oxford vaccine is, apparently, 70% effective (the announced result is 70.4%), compared to the 90% or higher for Moderna and Pfizer’s offerings. Except it’s simply not.

There were two groups in the vaccine study: one of about 9,000 people who were given a standard dose and then a booster shot of the same volume a month later; and a second group of about 3,000 people who were given a half-sized dose, and then a standard-sized booster. We should note at this point that the plan to divide the trial like this was in the original trial protocol, so we can be pretty confident that they haven’t just chopped the data up after the fact to make things look good. (EDIT: Although it is all quite complicated; see here.) 

The vaccine appears to have been 62% effective in the first lot, and 90% effective in the second. But if you’re given the vaccine, it will be either a full-dose/full-dose regimen or a half-dose/full-dose one, not some average of the two. So it’ll either be about 62% effective or about 90% effective, assuming those numbers are accurate.

Of course, “assuming those numbers are accurate” is the key phrase. We know there were 131 cases in total in the trial, and we know that there were 100 cases in the control group, and 31 among people who had the real vaccineBut only about 30 or so were in the half-dose group, and the smaller sample size means greater uncertainty.

Incidentally, it’s not completely clear why the smaller dose first is more effective. Andrew Pollard, the chief investigator, speculated in a Science Media Centre briefing on Monday morning that the smaller dose may have “primed” the immune response in some way. I’ve seen other scientists wondering whether it’s because the larger dose pushes the body to develop an immunity to the genetically modified virus that’s used to deliver the antigen. The immune system is complicated; I imagine we’ll find out more about what’s going on in the coming weeks.

There’s another point, which is that the headline figure also doesn’t tell us the impact on asymptomatic cases. The Pfizer and Moderna trials only looked at symptomatic cases: the  Oxford trial, on the other hand, asks all its subjects to swab themselves in the throat and nose every week (I’m on it, so I can vouch for this particular unpleasant duty), so it should catch anyone who’s got the virus, symptoms or no. The results don’t affect the headline figures — those only refer to symptomatic cases — but they are used to establish the effect of the vaccine on transmission. 

It is theoretically possible (but not very likely) that a vaccine could stomp heavily on the symptoms of a disease, so almost no one gets sick, but not stop people from actually getting the virus. By regularly swabbing asymptomatic people the study can see whether that’s the case. All we know so far is that there is an impact on transmission, but until all the data has been released, we won’t know how big that effect is; again, even Prof Ewer of Oxford hadn’t seen those numbers, and nor had Pollard, when he spoke to the SMC briefing.

There’s another level, as well, which is that no one who had had the actual vaccine — whether they got the half-dose or the full-dose regimen — got a “severe” case of Covid. Admittedly “severe” is defined as requiring hospitalisation, and obviously you can have quite a nasty case of Covid without ending up in hospital; but given how lethal this disease can be, it is nonetheless good news that no one ended up dying or in the ICU.

You may rightly say that all this sounds a bit woolly, and it kind of is. Here’s what we know: the vaccine, if administered correctly, probably works about 90% of the time on symptomatic cases, but we can’t be all that sure; it has some effect on asymptomatic cases, but we don’t know what; and no one who took it ended up in hospital, although we don’t know yet whether that means everyone just had a mild case of the sniffles or something more. It’s all good news, but very vague good news.

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So here are some bits of good news that are not vague. First, several million doses of this vaccine — which, as we’ve seen, definitely works, by the targets set — have already been made, and there is lots and lots more on the way. According to Pam Cheng of AstraZeneca (again speaking on the SMC briefing), by the end of December there will be enough actual vaccine to make about 20 million doses for the UK alone, of which about 4 million will already be in vials, ready to go. She thinks there will be about 200 million doses’ worth of material ready worldwide by the same time.

By the end of the first quarter of next year — so the beginning of April — she says there will be enough material for about 700 million doses worldwide, and about 40 million doses ready to go in the UK. And by the end of the year, they expect to have made 3 billion doses. The Serum Institute in India, the world’s biggest vaccine manufacturer, has a licence to manufacture it, so that’s a plausible number. Ewer said that it is estimated that something like two-thirds of the world’s children have received a vaccine made by the Serum Institute: “They are manufacturing on an enormous scale,” she said. “This is exactly what they specialise in, and that’s why we worked so hard to get them on board, because they can do large-scale cheap manufacture.”

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Better still, if the half-dose/full-dose regimen gets licensed, then that means it takes 25% less vaccine per patient. So your 40 million doses would vaccinate about 26 million Britons, instead of 20 million. Your 3 billion doses at the end of 2020 would vaccinate 2 billion people worldwide, not 1.5 billion.

That’s nowhere near enough for herd immunity, especially if the efficacy is on the lower end of the estimate, but it’s enough to vaccinate a huge chunk of at-risk groups and essential workers such as healthcare staff. And AstraZeneca and the manufacturers it has licensed the vaccine to will continue to churn out hundreds of millions more a month.

On top of this the Oxford vaccine, as has been widely reported, can be stored at normal fridge temperatures — between 2° and 8°C. It’s not that it would have been impossible to get huge amounts of the Moderna and Pfizer vaccines to, say, rural Malawi, with their -20°C and -80°C storage requirements, but it will be a damn sight easier with this one.

And, perhaps best of all, the Oxford vaccine looks as though it will sell at something like £2-3 a dose, according to Ewer. Pfizer is expected to sell its vaccine at about £15 and Moderna at more like £25. It is simply much more plausible that this can be bought and distributed in the large numbers required for use in the developing world. This is, says Ewer, partly because the viral vector vaccine technology is older – Johnson & Johnson has one for Ebola which is already being used — so “all the background work on deployment has been done”, while the mRNA vaccines are entirely novel (if exciting).

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I don’t know what this will mean for Britain in the short term. I was speaking recently to a senior scientist who helps advise the government about the mass testing that’s been piloted in Liverpool, and he mentioned that one possibility is that people who test positive have to isolate for a week, but then get a six-month passport saying they’ve had the disease and are safe. He suggested that the same system could be used for vaccines; it sounds plausible to me, with caveats, but whether it actually happens is anyone’s guess.

But the takeaway is that this, like the Pfizer and Moderna announcements in previous weeks, is fantastic news. More vaccines will come, and may be better in various ways, but this is a mass-availability, cheap, effective, easily-stored candidate that does everything you want. It will form the backbone of Britain’s response, and the world’s, and I’m really excited by it.

Now, I just can’t wait to find out what we get next Vaccine Candidate Announcement Day. See you next Monday!

 

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