A poster in India. Photo: Satish Bate/Hindustan Times via Getty

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? Itās so exciting!
This week, of course, it was the Oxford/AstraZeneca vaccine, one week after Moderna announced their results and two weeks after Pfizerās.Ā
The headline efficacy results of the Oxford trial are lower than for the other two vaccines. But itās 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 ā 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 Pfizerās offerings. Except itās 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 havenāt just chopped the data up after the fact to make things look good. (EDIT: Although it is all quite complicated; see here.)Ā
The vaccine appears to have been 62% effective in the first lot, and 90% effective in the second. But if youāre 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 itāll either be about 62% effective or about 90% effective, assuming those numbers are accurate.
Of course, āassuming those numbers are accurateā 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 vaccine.Ā But only about 30 or so were in the half-dose group, and the smaller sample size means greater uncertainty.
Incidentally, itās 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 āprimedā the immune response in some way. Iāve seen other scientists wondering whether itās because the larger dose pushes the body to develop an immunity to the genetically modified virus thatās used to deliver the antigen. The immune system is complicated; I imagine weāll find out more about whatās going on in the coming weeks.
Thereās another point, which is that the headline figure also doesnāt tell us the impact on asymptomatic cases. The Pfizer and Moderna trials only looked at symptomatic cases: theĀ Oxford trial, on the other hand, asks all its subjects to swab themselves in the throat and nose every week (Iām on it, so I can vouch for this particular unpleasant duty), so it should catch anyone whoās got the virus, symptoms or no. The results donāt affect the headline figures ā those only refer to symptomatic cases ā but they are used to establish the effect of the vaccine on transmission.Ā
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 thatās the case. All we know so far is that there is an impact on transmission, but until all the data has been released, we wonāt know how big that effect is; again, even Prof Ewer of Oxford hadnāt seen those numbers, and nor had Pollard, when he spoke to the SMC briefing.
Thereās another level, as well, which is that no one who had had the actual vaccine ā whether they got the half-dose or the full-dose regimen ā got a āsevereā case of Covid. Admittedly āsevereā 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. Hereās what we know: the vaccine, if administered correctly, probably works about 90% of the time on symptomatic cases, but we canāt be all that sure; it has some effect on asymptomatic cases, but we donāt know what; and no one who took it ended up in hospital, although we donāt know yet whether that means everyone just had a mild case of the sniffles or something more. Itās all good news, but very vague good news.
So here are some bits of good news that are not vague. First, several million doses of this vaccine ā which, as weāve seen, definitely works, by the targets set ā 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 dosesā worth of material ready worldwide by the same time.
By the end of the first quarter of next year ā so the beginning of April ā 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 worldās biggest vaccine manufacturer, has a licence to manufacture it, so thatās a plausible number. Ewer said that it is estimated that something like two-thirds of the worldās children have received a vaccine made by the Serum Institute: āThey are manufacturing on an enormous scale,ā she said. āThis is exactly what they specialise in, and thatās why we worked so hard to get them on board, because they can do large-scale cheap manufacture.ā
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.
Thatās nowhere near enough for herd immunity, especially if the efficacy is on the lower end of the estimate, but itās 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 ā between 2° and 8°C. Itās 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 Ā£2-3 a dose, according to Ewer. Pfizer is expected to sell its vaccine at about Ā£15 and Moderna at more like Ā£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 ā Johnson & Johnson has one for Ebola which is already being usedĀ ā so āall the background work on deployment has been doneā, while the mRNA vaccines are entirely novel (if exciting).
I donāt 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 thatās 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 theyāve 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 anyoneās 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 Britainās response, and the worldās, and Iām really excited by it.
Now, I just canāt wait to find out what we get next Vaccine Candidate Announcement Day. See you next Monday!
Ā
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