Why is the Oxford vaccine more effective at a lower dose?

‘When we use vaccines in babies, if you use different doses for priming, you can get a better or a worse boost’

Work on developing a vaccine against coronavirus at Oxford University (John Cairns)

The news from Oxford University on Monday that its coronavirus vaccine was effective has been widely welcomed, but it also caused some mystery after the trial results reported two different sets of numbers over whether the vaccine was effective.

Overall its effectiveness was rated at 70 per cent, but this was made up of two separate results looking at what happened when the vaccine was given in different doses.

When volunteers received two full doses of the vaccine, the medication, which is made from a modified chimpanzee cold virus, was 62 per cent effective at stopping infection.

But when participants were given a half dose followed weeks later by a full dose, the effectiveness increased substantially to 90 per cent.

How can a lower dose be more effective?

Professor Andrew Pollard, director of the Oxford vaccine group and chief investigator of the Oxford vaccine trial, explained: “In terms of what’s going on with immune response we think that by giving a smaller first dose we’re priming the immune system differently, we’re setting it up better to respond.

“What we don’t know at this moment is whether that difference is in the quality, or the quantity of the immune response and that’s something we're going to be digging into over the next weeks. We’ve already started some work to try to answer some of those questions, having only seen these results in detail over the weekend.”

He added: “It’s not a total surprise to find this. The best evidence we have that priming has an impact is from babies who are naive to these different germs. When we use vaccines in babies, if you use different doses for priming, you can get a better or a worse boost.”

Professor Sarah Gilbert, whose team have created the new vaccine, added the effect could be better because it actually mimics the way the body responds to an infection.

She said: “What we've tried to do with the vaccine is fool the immune system into thinking that there’s a dangerous infection there that it needs to respond to but doing it in a very safe way. So we get the immune response and we get the immune memory, and that’s there waiting and ready if the pathogen itself is then encountered.

“It could be that by giving a small amount of the vaccine to start with and following up with a bigger amount, that’s a better way of kicking the immune system into action and giving us the strongest immune response, and the most effective immune response.”

In all, around 10,000 volunteers received a full two-dose inoculation, with a smaller group, around 3,000 people getting the half dose, full dose jab.

Prof Pollard said that despite the smaller numbers, confidence was high, adding: “It’s still a highly significant result.”

He said more results and data would continue to come in over the next few weeks as the latest results were collected before 4 November.

The effect of the half dose on supply of the vaccine will not cause much trouble for AstraZeneca, which says it can flex the supply chain to provide both options.

Should the half-dose vaccine be the preferred option this could effectively double the amount of vaccines available to the UK by the end of this year from four million to eight million first doses.

The next full doses would not be needed until January, with AstraZeneca hopeful it can deliver 40 million doses by the end of March.