Oxford vaccine dosing error led to 90pc success rate by accident

Scientists surprised to see protection level improve to 90pc meaning vaccine stock will go further

A DOSING error during clinical trials led to the Oxford vaccine reaching 90 per cent efficacy by accident, it has emerged.

In the spring, scientists were left baffled as to why participants were experiencing much milder side effects than expected. When they checked, they found that they had received just half the dose given to 500 adults in earlier safety trials.

I nstead of restarting the t rial, researchers at Oxford University boosted the initial participants with a full dose while everyone who enrolled later received the full amount.

Trial results announced yesterday show that the “correct” vaccine dose achieved just 62 per cent efficacy while the “accidental” level was 90 per cent effective. “The reason we had the halfdose is serendipity,” said Mene Pangalos, a vice-president of Astrazeneca, the vaccine manufacturer. “We went back and checked... and we found out that they had underpredicted the dose of the vaccine by half.”

Once informed, regulators allowed the trial of more than 20,000 volunteers to continue, leading to results which were last night hailed by the Prime Minister as “incredibly exciting news”.

Prof Jonathan Van-tam, the deputy chief medical officer, yesterday said he shared “the euphoria” of scientists now that a third major vaccine had been shown to work.

Astrazeneca said 20 million doses could be available by the start of next year, with four million already waiting for use. The findings about the efficacy of the half-doses mean there could be enough for eight million people to begin their vaccination programme before Christmas.

In addition, up to five million doses of vaccines by Pfizer could be administered next month. Unlike the Pfizer jab, the vaccine from Astrazeneca can be kept at normal fridge temperatures, making it easier to store and distribute. Ministers hope that both jabs could begin being rolled out next month, with the NHS on standby to be ready to start administering vaccines from Dec 1.

The Medicines and Healthcare products Regulatory Agency is expected to be asked to begin assessing the AstraZeneca vaccine within days.

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THE news that Oxford University has succeeded in producing a vaccine which can protect up to 90 per cent of people is another step forward in the fight against coronavirus.

But in a curious development, it appears to work better if the first dose is halved.

The first interim Phase 3 trial data for the Oxford vaccine showed that two doses of vaccine protect about seven in 10 people, which is better than the seasonal flu jab, but worse than the Pfizer and Moderna jabs, which offer more than 90 per cent protection.

However, intriguing results show that for people who were given a half dose in the first round, the efficacy rises to 90 per cent.

Being able to use less vaccine for the first injection is good news, because it means the 100 million doses ordered by the UK government will go far further than previously thought. A smaller dose also has the added benefit of producing fewer side effects.

Prof Sarah Gilbert, lead researcher of the vaccine development programme, and professor of vaccinology at the University of Oxford, said: “We’ll be digging into the details of exactly why we get a better efficacy with a half dose but it may be because that better mimics what happens with a real infection.

“What we’ve always tried to do with the vaccine is fool the immune system into thinking that there’s a dangerous infection so we get new 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 big amount, that’s a better way of kicking the immune system into action and giving us the strongest and the most effective immune response.”

The vaccine also appears to reduce the likelihood of being admitted to hospital in people who get the virus, and there are early signs the jab prevents people transmitting the virus to others, which would make it the first vaccine to show it also stops the spread.

In contrast, results from the Pfizer and Moderna vaccines have only shown that they stop people from picking up the disease. The distinction is important as it will change how the vaccine is rolled out. Rather than vaccinating an entire population, or those most at risk, it may be possible to rapidly contain future outbreaks using “ring vaccination” where contacts of an infected person are rapidly immunised to prevent onward transmission. The strategy has been successfully used to beat Ebola outbreaks in Africa.

The Oxford vaccine, officially called Chadox1 ncov-19, is made from a virus (Chadox1), which is a weakened version of a common cold virus – or adenovirus – that causes infections in chimpanzees. It has been genetically changed so that it is impossible for it to grow in humans.

Scientists have also added genetic material to the harmless carrier virus so that it can make a specific type of coronavirus proteins, called “spike proteins”. These are found on the surface of the virus and play an essential role in latching on to receptors on human cells so the virus can gain entry and cause infection.

Once the spike proteins are produced in the body, the immune system will notice there is a foreign invader and mount a defence response. It means that the body will already be primed to fight off another infection if it comes across the real virus in future.

The Oxford “viral vector” jab is dif

‘We’ll be digging into the details of exactly why we get a better efficacy with a half dose’

ferent from the Pfizer and Moderna “messenger RNA” vaccines which work by sending genetic code into cells instructing them to make the spike protein themselves.

No vaccine has been successfully created in this way before, so it is far more expensive to produce.

And because the Pfizer vaccine relies on a live piece of RNA it needs to be kept at temperatures of -103F (-75C) to avoid the genetic code being destroyed.

In contrast the Oxford vaccine, and the Moderna version, can be stored at usual fridge temperatures of between 35F and 46F (2C and 8C). The Oxford vaccine is also likely to be far cheaper, costing just a few pounds compared with around £15 for Pfizer and £25 for Moderna.

Usually vaccines can take 10 to 15 years of development to reach the clinic, but scientists at Oxford had already started working on a platform which would allow speedy development for an unknown “Disease X”.

They began working on the jab in January and the human trials began in April.

Astrazeneca said there were four million doses already in vials ready for distribution, but regulators must give the green light before distribution can begin.

That process is likely to take several weeks but the first jabs are expected to take place in Britain this year.