December 4, 2020

Oxford coronavirus vaccine is safe and triggers robust immune response, phase 2 study finds – Daily Mail

https://www.dailymail.co.uk/news/article-8735759/Oxford-coronavirus-vaccine-safe-triggers-robust-immune-response-phase-2-study-finds.html

Oxford University’s coronavirus vaccine triggers a ‘robust’ response from the immune system and appears to work in older people, a study revealed today.

Scientists behind the project this morning published the results of an early trial of the jab, which found it created strong signs of immunity in 99 per cent of people.

The second-phase study included 560 people, most of whom were white and British, and showed that people across all age groups seemed to react equally well to the jab. It adds to data published in July suggesting it would work safely for under-55s.

It marks another breakthrough in the race to develop a vaccine to prevent Covid-19, after jabs made by Moderna and Pfizer and BioNTech were both revealed to be around 95 per cent effective within the past week.

Oxford’s results are from an earlier stage of testing so cannot estimate how well the vaccine protects against Covid, but are still a positive step. Detailed results about how well it works are expected within weeks, the university said.

The research showed that people in all age groups developed antibodies – virus-destroying substances made by the immune system – within 28 days of their first dose of the vaccine, and these were boosted further after the second dose.

It showed that the vaccine caused more side effects than a fake jab but that these were ‘mild’ and more common in young people than older participants.

Within the first week after having the injection more than eight out of 10 under-55s said their arm hurt and and they later experienced tiredness, muscle aches or headaches.

Britain has pre-ordered 100million doses of Oxford’s jab, which is being made with pharmaceutical firm AstraZeneca, so if it works and can be manufactured fast enough it could be used to protect the majority of the UK’s population. 

The jab could cost as little as £2 per dose, which makes it significantly cheaper than the £15-£28 for Pfizer and Moderna’s vaccines, which will cost the UK tens of millions of pounds.

Scientists today described the news as ‘promising’ and ‘positive’, adding that the UK’s order could be big enough to reach herd immunity if the vaccine comes good. Health Secretary Matt Hancock said in a tweet: ‘There is still much work to be done, but this is a really encouraging set of findings’.

Oxford University scientists published the results of their second-phase trial of the jab in medical journal The Lancet this morning, showing that it appears to work in adults of all ages

Oxford University scientists published the results of their second-phase trial of the jab in medical journal The Lancet this morning, showing that it appears to work in adults of all ages

Oxford University scientists published the results of their second-phase trial of the jab in medical journal The Lancet this morning, showing that it appears to work in adults of all ages

Oxford published the results from tests of its vaccine, named ChAdOx1 nCov-2019, in UK medical journal The Lancet today. 

Volunteers in the trial demonstrated similar immune responses across all three age groups – they had been split into 18-55, 56 to 69, and 70-plus. 

Observations of the 560 adults – including 240 over the age of 70 – found the vaccine was actually better tolerated and caused fewer side effects in older people.

The news that the jab appears to be safe and effective for older people is a huge step forward for the project, because this is the group most at risk of severe Covid-19 and death.

Health officials in the UK have suggested that vaccines for younger adults and children are lower priority, and that vaccinating the over-50s and people with serious health conditions would cover the vast majority of people likely to die.

Professor Deborah Dunn-Walters, chair of the British Society for Immunology, described the announcement as ‘positive’.

She said: ‘While this is an ongoing study, the initial results are encouraging.

‘The vaccine appears to be well tolerated in all age groups, with older individuals reporting fewer side-effects.’

The Faculty of Pharmaceutical Medicine’s Dr Gillies O’Bryan-Tear explained: ‘The ageing of the immune system in older people can lead to lower efficacy of vaccines. 

‘This is especially important as Covid has much higher lethality in older people. 

‘One clue to this from the current study is that older people reacted less to the vaccine – fewer fevers, less injection site pain and swelling – but encouragingly, the immune responses in the older patients were indistinguishable from those in younger patients. 

‘This suggests, but does not prove, that the protection against the illness will be similar in the elderly and the young.’ 

And Dr Michael Tildesley, a Warwick University epidemiologist who advises SAGE, said the vaccine could be a ‘game changer’.

He told BBC Breakfast the number of doses acquired by the Government could push the UK towards ‘that magic herd immunity’

Successfully protecting older people was the ‘really key thing’, he said.  

Volunteers in the study were split into two groups and either received two doses of the real vaccine candidate or a placebo meningitis vaccine. 

The placebo is given so scientists can be sure that any side effects people report are actually caused by the vaccine and not just the injection itself or psychological. 

No serious health problems related to the vaccine were seen in any of the participants, the researchers said.

Dr Maheshi Ramasamy, investigator in the Oxford Vaccine Group and a consultant doctor, said: ‘Older adults are a priority group for Covid-19 vaccination, because they are at increased risk of severe disease, but we know that they tend to have poorer vaccine responses.

‘We were pleased to see that our vaccine was not only well tolerated in older adults, but also stimulated similar immune responses to those seen in younger volunteers.

‘The next step will be to see if this translates into protection from the disease itself.’

The vaccine is known as a recombinant viral vector vaccine and is made using a piece of the real coronavirus but not enough of it to cause illness.

In this case, scientists modified a cold virus found in monkeys to make it look like the coronavirus by attaching the ‘spike’ proteins found on the Covid virus to the outside.

This means that when the vaccine is injected, the spikes make the body think it is seeing the coronavirus and the immune system attacks it. 

In the process it develops an understanding and memory of how to fight off any virus that has the same spikes on the outside, so if it encounters the coronavirus for real it should know immediately how to destroy it before it can cause Covid-19.

Although the early phases of Oxford's trial have not tested the vaccine on many people in non-white groups or people with serious health conditions, a bigger study has recruited people from all over the world to check the jab works on everyone (Pictured: A woman in Brazil receives a dose of the vaccine)

Although the early phases of Oxford's trial have not tested the vaccine on many people in non-white groups or people with serious health conditions, a bigger study has recruited people from all over the world to check the jab works on everyone (Pictured: A woman in Brazil receives a dose of the vaccine)

Although the early phases of Oxford’s trial have not tested the vaccine on many people in non-white groups or people with serious health conditions, a bigger study has recruited people from all over the world to check the jab works on everyone (Pictured: A woman in Brazil receives a dose of the vaccine)

Oxford's vaccine is being produced by Cambridge-based pharmaceutical firm AstraZeneca

Oxford's vaccine is being produced by Cambridge-based pharmaceutical firm AstraZeneca

Oxford’s vaccine is being produced by Cambridge-based pharmaceutical firm AstraZeneca

Oxford’s announcement comes after late-stage clinical trial results were reported by pharma firms Moderna and Pfizer and BioNTech this week.

Pfizer and BioNTech yesterday said the final results of their clinical trial suggested their vaccine was 95 per cent effective, just days after Moderna claimed its own jab showed efficacy of 94.5 per cent.

UK DRUGS WATCHDOG ON STANDBY FOR TRIAL DATA FOR FIRST VACCINE

Britain’s drug regulator yesterday confirmed it is waiting for Pfizer to send over the full results of its final Covid-19 vaccine trial so it can consider approving it as the first ever coronavirus jab.

The pharmaceutical giant yesterday claimed it can now prove its vaccine is safe, up to 95 per cent effective and works in older people.

The US company, most famous for making Viagra, announced it would submit the necessary data to regulators in America and the UK ‘within days’, bolstering hopes that Britain could embark on its major Army-backed operation to vaccinate millions of people from as soon as December 1. 

UK drug regulator the MHRA has been doing a ‘rolling review’ of the vaccine and could, as a result, complete the approval process within a matter of days of receiving the application from Pfizer and BioNTech, a German firm involved in making the jab. 

Dr June Raine, the MHRA’s chief executive, said: ‘The results reported by Pfizer today are very encouraging and add to their announcement from last week. 

‘We look forward to receiving the full results of the trials as soon as possible, after which we will rigorously assess the evidence of safety and effectiveness of the vaccine.’

Britain has already pre-ordered 40million doses of the vaccine and could be set to get 10m of those next month, with the NHS gearing up start dishing it out within a fortnight. Professor Stephen Powis, NHS England’s medical director, today said the health service was ‘working incredibly hard’ to prepare.

Pfizer and BioNTech’s final trial results showed that only eight people out more than 20,000 who got the vaccine caught coronavirus, compared to 162 who were given a fake jab. A total of 10 people got severe Covid-19, one of whom had been given the real vaccine.

An independent safety committee ‘has not reported any serious safety concerns related to the vaccine’ since the final stage trial began in July, Pfizer said. Side effects were limited – the most common was fatigue, which 3.8 per cent of people got, and headaches (2 per cent).

The announcement is an improvement on Pfizer’s early estimate that the vaccine was 90 per cent effective, and comes just days after rival firm Moderna claimed its own jab was 94.5 per cent effective, which sparked fears the UK had hitched its wagon to the wrong project because No10 hadn’t bought any doses.

The UK is now in the process of getting these through regulatory approval and will buy millions of doses if they’re approved.

Up to five million people could be vaccinated with Pfizer’s jab before the end of the year if the process goes smoothly.

Oxford’s vaccine is expected to be considerably cheaper than either of those, has been ordered in huge quantities and will be easier to store and deliver.

While Moderna’s is expected to cost between £24 and £28 per dose, and Pfizer’s around £15 per dose, Oxford’s could cost just £2.23.

Manufacturer AstraZeneca said it would produce the first batch of vaccines ‘at cost’, meaning it won’t profit from them, although it could up the price in the future.

Storage and transport of Oxford’s vaccine is likely to be cheaper, too, with previous versions of the same technology suitable for storing at room temperatures.

Pfizer and Moderna both say their vaccines must be frozen during transport and then kept cold up until the point they’re used in a clinic.

Pfizer’s will be particularly challenging because it has to be kept at an ultra-cold -70°C (-94°F) throughout the supply chain, which requires specialist freezers.

Moderna’s is less difficult because it only needs to be frozen during transport, at a temperature that normal freezers are capable of reaching, and can then be kept in a fridge.

Oxford’s can be kept stable in temperatures between 2°C and 8°C, meanwhile, meaning it could be kept in a standard fridge at all times so no new equipment would need to be bought.

Today’s Lancet study also found the vaccine, being developed with AstraZeneca, was less likely to cause local reactions at the injection site and symptoms on the day of vaccination in older adults than in the younger group.

Adverse reactions were mild – injection-site pain and tenderness, fatigue, headache, feverishness and muscle pain – but more common than seen with the control vaccine.

Thirteen serious adverse events occurred in the six months since the first dose was given, none of which were related to either study vaccine.

The authors note some limitations to their study, including that the participants in the oldest age group had an average age of 73-74 and few underlying health conditions, so they may not be representative of the general older population, including those living in residential care settings or aged over 80.

Phase three trials of the vaccine are ongoing, with early efficacy readings possible in the coming weeks.

UK authorities have placed orders for 100million doses of the vaccine – enough to vaccinate most of the population – should it receive regulatory approval.

The Oxford findings come after Pfizer and BioNTech announced that their vaccine candidate has shown 95 per cent efficacy, with a 94 per cent effectiveness in those aged 65 and over.

Forty million doses of that vaccine have been bought by the UK, with rollout potentially starting in early December if the jab is given the green light by regulators.

Earlier in the week US biotech firm Moderna released data suggesting its vaccine is almost almost 95 per cent effective.

HOW DO THE OXFORD, MODERNA AND PFIZER/BIONTECH VACCINES COMPARE? 

Moderna and Pfizer/BioNTech have both released interim results of the final stage clinical trials of their vaccines, with both suggesting they are extremely effective. 

Oxford University has published the findings from its second phase, which show the jab provokes an immune response and is safe to use – it is not yet clear how well it protects against coronavirus in the real world.

Here’s how they compare: 

PFIZER (US) & BIONTECH (DE)

mRNA vaccine – Genetic material from coronavirus is injected to trick immune system into making ‘spike’ proteins and learning how to attack them.

mRNA vaccine – both Moderna’s and Pfizer and BioNTech’s vaccines work in the same way.

Recombinant viral vector vaccine – a harmless cold virus taken from chimpanzees was edited to produce the ‘spike’ proteins and look like the coronavirus.

94.5% effective (90 positive in placebo group, 5 positive in vaccine group) .

95% effective (160 positive in placebo group, 8 positive in vaccine group).

Efficacy is unknown because trials are not complete. It provoked a ‘robust’ immune system response in 99% of people in early trial. 

Moderna confirmed it will charge countries placing smaller orders, such as the UK’s five million doses, between £24 and £28 per dose. US has secured 100million doses for $1.525billion (£1.16bn), suggesting it will cost $15.25 (£11.57) per dose.

The US will pay $1.95bn (£1.48bn) for the first 100m doses, a cost of $19.50 (£14.80) per dose.

Expected to cost £2.23 per dose. The UK’s full 100m dose supply could amount to just £223million.

UK has ordered five million doses which will become available from March 2021. Moderna will produce 20m doses this year, expected to stay in the US. 

UK has already ordered 40million doses, of which 10million could be available in 2020. First vaccinations expected in December.

UK has already ordered 100million doses and is expected to be first in line to get it once approved.

What side effects does it cause? 

Moderna said the vaccine is ‘generally safe and well tolerated’. Most side effects were mild or moderate but included pain, fatigue and headache, which were ‘generally’ short-lived. 

Pfizer and BioNTech did not produce a breakdown of side effects but said the Data Monitoring Committee ‘has not reported any serious safety concerns’.

Oxford said there have been no serious safety concerns. Mild side effects have been relatively common in small trials, with many participants reporting that their arm hurt after the jab and they later suffered a headache, exhaustion or muscle pain. More data is being collected.

What do we know about Oxford’s coronavirus vaccine?

When will it be ready? 

Results of a trial testing how well it works are expected to be ready for publication within weeks, the team said today.

Once the data is ready, it will then be examined by the healthcare regulator MHRA, which will decide if it is suitable to use on the public.

Officials say the NHS is gearing up to administer a Covid-19 vaccine as soon as December, if one is proven to work.

When will you be able to get one? 

Despite the fact the Government has secured a deal for 100million doses, only about four million are likely to actually be available by the end of this year, vaccine chief Kate Bingham has revealed. This would cover just two million people.

The first wave of vaccines would not be good enough to allow society to immediately return to normal, Ms Bingham said. 

A priority list for vaccination in the UK has been drawn up officials, putting care home residents and workers, those over the age of 80 and healthcare workers at the front of the queue, encompassing at least six million people.

Will it work?  

Early trials, including today’s results, suggest the vaccine does stimulate the immune system in the right way and forces the body to produce antibodies specific to the coronavirus.

This means the jab should be effective at stopping Covid-19, but what proportion of people it works in and how long the protection lasts remain to be seen. 

Professor Sarah Gilbert, leader of the Oxford team, said before trials began that she was ’80 per cent’ confident of its success, ‘based on other things that we have done with this type of vaccine’. 

What obstacles have the team faced? 

Trials were paused three times to investigate serious events in volunteers. 

On two occasions, in July and September, trial participants had developed symptoms that were feared to have been caused by the jab. And one man in Brazil died of Covid-19 in October— but was reported to have been given the placebo jab.  

In each event, independent reviewers judged it was safe to continue the jab experiments after they were stopped for several days. 

Today’s update said there were 13 serious health problems during the second phase of the trial, but none of them were linked to the vaccine. 

How does it work? 

The vaccine is known as a ‘recombinant viral vector vaccine’. It is made using a piece of the virus which is unable to cause illness.

In this case, a common cold virus (adenovirus) from chimpanzees has been used and edited to make it develop the spikes seen on the outside of the coronavirus.

If the vaccines can successfully mimic the spikes inside a person’s bloodstream, and stimulate the immune system to create special antibodies to attack it, this could train the body to destroy the real coronavirus if they get infected with it in future. 

Is it safe?

Probably, based on the initial results of trials. But this won’t become clear until the vaccine completes stage three clinical trials. It won’t be rolled out unless it is proven to be safe. 

Even though it has been made at lightning speed – it’s gone through the stages of vaccine development that usually take five years in just four months – Professor Gilbert said that none of the normal safety steps had been missed out. 

Chimpanzee adenoviral vectors are a very well-studied vaccine type, having been used safely in thousands of subjects. 

How has it been tested?

Some 1,100 British people were involved in the Phase 1 trial. Phase II enrolled around 11,000 adults and children across the UK.  

More than 50,000 people worldwide will take part in Phase III trials, scientists involved have said. Half will be given the real vaccine candidate, while others will receive a placebo.

In September AstraZeneca said the jab had been given to 18,000 people across the world so far.

Who made the vaccine and who owns it?

Clinical teams at the Oxford University’s Jenner Institute and Oxford Vaccine Group began developing the ChAdOx1 nCoV-19 vaccine in January. 

After they partnered up with pharmaceutical giant AstraZeneca in May, the jab was named AZD1222. 

The intellectual rights to its vaccine are owned by the University of Oxford and a spin-out company called Vaccitech. 

How does it compare to other vaccines?  

The Oxford vaccine is the same as that being produced by Janssen, which is also a recombinant vector vaccine using a human adenovirus. GSK/Sanofi’s works in a similar way, but with the addition of an adjuvant – which can give the immune system a boost.

But jabs produced by Pfizer/BioNTech and Moderna – the first to have results published this month – are known as messenger RNA (mRNA) vaccines. 

They insert genetic code from the virus into the body to prompt it to make the spike proteins. This provokes the immune system to make antibodies. This experimental technology has never previously been proven in humans. 

A team at Imperial College London is also among those developing an RNA vaccine candidate. It will try to transport the RNA inside liquid droplets injected into the bloodstream.

Which other countries have secured doses?

France, Germany, Italy and the Netherlands have secured 400million doses. Australia has secured doses for its population of 25million people. The US has secured 100million doses. The Serum Institute of India has also secured a billion doses. AstraZeneca has said that doses will be handed out equitably.

How much does it cost?

The vaccine may cost as little as £2.23 per dose, which compares to the estimated £15 per dose of Pfizer/BioNTech.

AstraZeneca has said it will not profit from the it, but may earn extra royalties if the coronavirus becomes an endemic infection like flu. The US has spent $1.2 billion (£930million) securing doses, meaning they are worth $4 (£3.10) each.