THE blueprint for the Oxford Covid vaccine was already on standby even before the World Health Organisation’s China office was first notified of a mysterious new ‘Wuhan pneumonia’ on New Year’s Eve last year.

By January 3, 44 cases of the disease had been reported, with some of the patients - 11 of whom were were “severely ill” - identified as dealers or vendors at Huanan Seafood market.

Thousands of miles away in Oxford, Professor Sarah Gilbert believed the world could be witnessing the long-awaited emergence of Disease X - and her team were ready for it.

Prof Gilbert had been working on vaccine technology since the 1990s, initially trying to develop an inoculation for malaria and then a universal flu vaccine capable of protecting against all strains of influenza.

The Herald: Sarah Gilbert, professor of vaccinology at Oxford University and co-founder of its spin-out company Vaccitech, which specialises in developing novel vaccinesSarah Gilbert, professor of vaccinology at Oxford University and co-founder of its spin-out company Vaccitech, which specialises in developing novel vaccines

In 2014 she led the first trial of an Ebola vaccine, and when a previous novel coronavirus - Middle East respiratory syndrome (Mers) - began claiming lives she headed to the epicentre of the outbreak in Saudi Arabia to study the virus.

Mers, which spread from camels to humans in 2012, is more deadly that the coronavirus which causes Covid-19, but much less able to pass from person to person.

Cases have been reported in 27 countries, including the UK, and there have been 858 known deaths.

However, it was Mers which paved the way to a Covid vaccine by spurring Prof Gilbert and her team develop the ChAdOx-1 vaccine - short for Chimpanzee Adenovirus Oxford One.

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This was a cutting edge ‘plug and play’ vaccine created by taking an adenovirus which causes the common cold in chimps, genetically modifying it so that it cannot cause an infection in humans, and using that as an all-purpose building block for future vaccines.

The scientists have compared it to a sort of “genetic postman” in the sense that all they need to do is alter its contents so that it can recognise and attack a new virus.

The fact that Mers and SARS-CoV-2 - the virus which causes Covid-19 - are both coronaviruses also put the researchers at an advantage, because both have the distinctive spike protein which ChAdOx-1 had been designed to identify and attack.

“We had a huge head start,” Professor Andrew Pollard, the director of the Oxford Vaccine Group told the BBC last week.

“If this had been a completely unknown virus, then we’d have been in a very different position.”

By the time alarm bells started ringing over ‘Wuhan pneumonia’, 330 people had been given ChAdOx1-based vaccines for diseases ranging from flu to Zika virus, and human trials on the version for Mers were just beginning.

By January 11, scientists in China had untangled and published the genetic code for the novel coronavirus which by then had caused its first known fatality.

“We’d been planning for disease X, we’d been waiting for disease X, and I thought this could be it,” Prof Gilbert said, referring to the term used by the WHO to describe a hypothetical future pathogen with epidemic or pandemic potential.

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Over the course of a weekend, the team in Oxford took the genetic code and used it to reboot their ChAdOx-1 vaccine with a new genetic instruction manual - this time designed to recognise and attack the coronavirus behind Covid-19.

Trialling a vaccine requires three stages before it can go to regulators.

In Phase One - following initial animal tests - the vaccine is tested on a small number of healthy volunteers to check that it is safe.

In Phase Two, the trial is expanded to include a larger number of people in order to further assess the safety. A placebo will also be introduced to determine whether the vaccine is effective.

In the case of the Oxford vaccine trial, participants from centres across the UK - including Glasgow and Edinburgh - were randomly placed into groups where some were given the Covid vaccine and some an existing vaccine against meningitis.

The study was “single-blinded”, meaning that the researchers knew which group was getting which vaccine - but participants did not.

In Phase Three, the trial is ramped up to include thousands of volunteers from different countries. In total, 24,000 people from the UK, Brazil and South Africa have taken part to date in the Oxford vaccine trial.

This stage enables scientists to identify any side effects (none serious) and gauge the correct dosing.

One of the surprising findings has been that the vaccine appears to be more effective - possibly up to 90% effective - when participants receive a half dose followed by a full dose weeks later.

The Herald: The building block, or 'vector', of the Oxford vaccine is a modified cold virus which normally infects chimpanzees The building block, or 'vector', of the Oxford vaccine is a modified cold virus which normally infects chimpanzees

This discovery was a “lucky accident” according to Dr Mene Pangalos, head of biopharmaceutical research at AstraZeneca - the commercial partner behind the Oxford vaccine.

The researchers realised they had inadvertently given some volunteers a half dose when they noticed that this sub-group were reporting much milder side effects, such as fatigue, headaches and arm aches.

“That, in essence, is how we stumbled upon doing half dose-full dose (group),” Dr Panglos told Reuters. “Yes, it was a mistake.”

Despite the error, the team decided to retain the half-dose group and to administer the second, full dose booster as scheduled.

The results showed 90% efficacy at one and a half doses compared to 62% for the two full doses.

It is not yet clear exactly why the half dose works better but one theory is that the full dose primes the body’s immune system to attack the vector - the chimp adenovirus - so that when the second dose is given it is less effective.

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Participants have blood drawn to check whether the vaccine has triggered the production of antibodies and T cells (it did) and anyone who develops possible Covid symptoms (as a result of acquiring the infection naturally in the environment) is given a PCR test.

In this way, the scientists can establish whether participants vaccinated against Covid are less likely to develop the disease than those given a placebo.

On this measure, those inoculated with the one and a half Covid dose were 90% less likely to develop the disease.

That does not necessarily mean they are 90% less likely to contract the infection, but it means they do not become ill - which is key for reducing pressure on health services.

However, there was some tantalising evidence that the Oxford vaccine might also curb transmission, potentially “stopping the virus in its tracks”.

Work is ongoing to enrol thousands more trial participants from Japan, Russia and the United States, up to a target of 60,000, but on Friday the UK's Medicines and Regulatory Agency (MHRA) confirmed that it had received a formal request from the Department of Health to review the vaccine's safety and effectiveness - the final step before it is approved for use.

The process seems fast - the vaccine only entered human trials on April 23 - but in reality it has already completed all the necessary steps.

Funding for Covid vaccine research poured in as the virus swept the globe, so far killing at least 1.4 million people and - probably just as pertinent to investors - ravaging western economies.

Money ensured that the normal delays associated with vaccine research - such as applying for grants or securing a manufacturer - were swept aside, while the prevalence of the virus and its publicity ensured swift recruitment of the thousands of volunteers needed.

At one point, the Oxford researchers were even able to afford to charter a private jet to travel to Italy - where vaccine batches were being manufactured - to collect stocks and fly back in time for the next day's clinic.

Four million doses of the Oxford vaccine are complete and ready to be rolled out.

Along the way, the MHRA has been tracking data from the trial on a staggered basis so the review will not start from scratch, as it would normally.

A spokeswoman for the MHRA said: "The total review time therefore should be quicker than usual.

"However, should the MHRA authorise the vaccine the overall data will have been sufficient to conclude on its safety, quality and efficacy, and the necessary robust requirements are not compromised."

As millions - rather than thousands - are immunised, very rare side effects may emerge.

But the same is true of any medicine and must be balanced against the harm already wreaked by Covid.