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Cambridge joins the coronavirus vaccine race

Cambridge University has joined the global race to find a coronavirus vaccine and could begin clinical trials within months.

Scientists at the prestigious institution are working on a vaccine they hope could protect against other coronaviruses, as well as the one that causes Covid-19.

It won’t target the ‘spike’ protein on the outside of the virus, as other scientists are attempting, but will try to mimic a more complete version of the pathogen itself.

And the team are trying to make the jab needle-free, designing it so it can instead be administered using a burst of air from a jet injector, which forces the liquid through the top layer of skin using pneumatic pressure. 

They say the type of vaccine they’re making has proven safe in the past and appeared to work for in trials for SARS, a similar type of coronavirus disease.

The British Government has given the researchers £1.9million to develop and test out their vaccine in the hope that it will prove successful. 

The university’s fierce rivals in Oxford are already in large-scale human trials of their own experimental injection, with hundreds of millions of orders already placed by governments around the world.

Hopes of the Covid-19 pandemic coming to an end and life returning to normal mostly hinge on a working vaccine being found so that people can live without fear of the virus.

Scientists at Cambridge University (Pictured: Queens College at the university) have joined the global race to find a vaccine that works against Covid-19

Scientists at Cambridge University (Pictured: Queens College at the university) have joined the global race to find a vaccine that works against Covid-19

The vaccine is being developed by Cambridge scientists and a spin-off company called DIOSynVax, dedicated solely to producing vaccines.

It is different to jabs being made by Oxford and Imperial because it uses whole DNA — two strands of genetic material — instead of RNA, which contains one strand.  

The researchers say this makes the vaccine more stable and versatile, allowing it to be freeze-dried and used in the jet injector delivery system.

This would make it particularly helpful in poorer countries where it is difficult to keep the product refrigerated or to get access to needles and syringes, for example.

And it also focuses on different parts of the coronavirus than other vaccines in development are doing.

While most choose to target the spike proteins on the outside of the coronavirus, the Cambridge team said immunity based on antibodies produced against these spikes may be weak and short-lived. 

Research has found that not everybody who gets Covid-19 develops this antibody immune response, and some of those who do only have low levels of it.

A different type of immunity called T cell immunity, however, appears much stronger and this is what the Cambridge team want to develop. 

To do this they are focusing on developing a wider range of sections of the virus so the vaccine would still recognise the virus if its spikes mutated, and which could also make it effective against other types of coronavirus.

Graphic explains how the Cambridge University vaccine could work, and how it differs to the ones made by Oxford and Imperial College London

Graphic explains how the Cambridge University vaccine could work, and how it differs to the ones made by Oxford and Imperial College London

The team also added that interaction between antibodies and the spike proteins can sometimes trigger an immune system over-reaction which could be harmful.

Dr Rebecca Kinsley, chief operating officer of DIOSynVax and a PhD researcher at the University of Cambridge, said: ‘Most research groups have used established approaches to vaccine development because of the urgent need to tackle the pandemic. 

‘We all hope the current clinical trials have a positive outcome, but even successful vaccines are likely to have their limitations – they may be unsuitable for vulnerable people, and we do not know how long their effects will last for, for example.

HOW DOES A JET INJECTED VACCINE WORK? 

Jet injection is a way of administering a vaccine without using a needle and syringe.

It has been used for decades but is less common than the standard ‘jab’ form of vaccination.

It works in a similar way, however, and still contains a small quantity of liquid which holds the vaccine inside it, and inserts this into the body where it is picked up by the immune system.

A jet injector gun forces the vaccine liquid through the top layer of skin in an extremely high-pressured, tiny stream which is propelled by gas pressure inside the device.

It uses pneumatic pressure to force the liquid through the top layer of skin where it can be absorbed into the bloodstream.

One benefit of the jet injector is that it is almost contact-free – except that the end of the gun must touch the skin – so the risk of cross-contamination may be lower than with needles, which have the potential to be re-used in unsafe environments or poor countries.

It is possible, however, that bodily fluids can get onto the gun and carried to the next patient.

‘Our approach – using synthetic DNA to deliver custom designed, immune selected vaccine antigens – is revolutionary and is ideal for complex viruses such as coronavirus. 

‘If successful, it will result in a vaccine that should be safe for widespread use and that can be manufactured and distributed at low cost.’

Professor Jonathan Heeney, founder of DIOSynVax added: ‘Our strategy includes targeting those domains of the virus’s structure that are absolutely critical for docking with a cell, while avoiding the parts that could make things worse. 

‘What we end up with is a mimic, a synthetic part of the virus minus those non-essential elements that could trigger a bad immune response.’

To develop the vaccine the DIOSynVax team have harvested genetic material from all known coronaviruses, including those in bats – the natural hosts – and ones that infect humans but cause mild illnesses like common colds.

They hope this will help to make the vaccine more general and able to build up immunity against numerous types of virus in case another one jumps to humans in the future. 

Using the genetic material the researchers can work out how to produce antigens of the coronavirus. 

An antigen is a part of the virus that the body recognises as an invader, and which triggers an attack from the immune system.

The spike protein is one type of antigen, but the Cambridge team have tried to incorporate other sections of the virus as well to tackle more bases.  

When the DNA coding for these antigens is inserted into the body, it forces the immune system to reproduce them and then immediately learn how to destroy them, which in turn generates immunity in case someone gets the virus for real.

The researchers have got funding from UK Research and Innovation and will be trialled at University Hospital Southampton NHS Trust, potentially as soon as autumn.

Professor Saul Faust, director of the NIHR Southampton Clinical Research Facility, said: ‘It is critical that different vaccine technologies are tested as part of the UK and global response to the pandemic as at this stage no one can be sure which type of vaccine will produce the best and most long-lived immune responses.

‘It is especially exciting that the clinical trial will test giving the vaccine through people’s skin using a device without any needles as together with stable DNA vaccine technology this could be a major breakthrough in being able to give a future vaccine to huge numbers of people across the world.’ 

Cambridge’s attempt to make a vaccine comes alongside dozens of other institutions around the world all scrambling to develop one that works.

There are more than 100 being made and in various stages of testing and top medics and public health officials expect one to be completed some time next year.

Although the Holy Grail would be a ‘sterilising’ vaccine, which completely destroys and stops the virus, scientists say it is more likely they can make one that simply prevents people from dying and turns Covid-19 into a mild cold-like disease.

Russia is the only country to have officially approved a vaccine but it came under heavy criticism for not doing proper clinical trials and scientists are sceptical of it. 

WHICH TOP VACCINE CANDIDATES HAVE THE UK SECURED DEALS FOR? 

1. GlaxoSmithKline and Sanofi Pasteur: 60million doses 

The Government revealed on July 29 it had signed a deal with pharmaceutical giants GlaxoSmithKline (GSK) and Sanofi Pasteur

If the vaccine proves successful, the UK could begin to vaccinate priority groups, such as frontline health and social care workers and those at increased risk from coronavirus, as early as the first half of next year, the Department for Business, Energy & Industrial Strategy (BEIS) said. 

Human clinical studies of the vaccine will begin in September followed by a phase 3 study in December. 

The vaccine is based on the existing technology used to produce Sanofi’s seasonal flu vaccine. Genetic material from the surface protein of the SARS-CoV-2 virus is inserted into insect cells – the basis of Sanofi’s influenza product – and then injected to provoke an immune response in a human patient.  

2. AstraZeneca (manufacturing University of Oxford’s): 100million

AstraZeneca, which is working in partnership with Oxford University, is already manufacturing the experimental vaccine after a deal was struck on May 17.

Professor Sarah Gilbert, who is leading the Oxford team, is confident the jab could be ready for the most vulnerable people by the end of the year.

Her comments came after the results from the first phase, published in The Lancet on July 20, showed promise.

The team have genetically engineered a virus to look like the coronavirus – to have the same spike proteins on the outside – but be unable to cause any infection inside a person. This virus, weakened by genetic engineering, is a type of virus called an adenovirus, the same as those which cause common colds, that has been taken from chimpanzees. 

3.  BioNTech/Pfizer: 30million 

US drug giant Pfizer – most famous for making Viagra – and German firm BioNTech were revealed to have secured a deal with the UK Government on July 20.

It reported positive results from the ongoing phase 2/3 clinical trial of one called BNT162b1 on July 1.  The company is still running phase 2 trials at the moment.

Pfizer’s vaccine is one called an mRNA vaccine, which do not directly inject bits of the virus into the body but send genetic material.

mRNA vaccines programme the body to produce parts of the virus itself by injecting the body with a molecule that tells disease-fighting cells what to build. The immune system then learns how to fight it.

4. Valneva: 60million 

The Government has given Valneva — whose vaccine is understood to be in the preclinical stages of development — an undisclosed amount of money to expand its factory in Livingston, Scotland. 

While the Government revealed a 60million dose deal on July 20, the company said it had reached agreement in principle with the UK government to provide up to 100million doses. 

Valneva’s jab is an inactivated whole virus vaccine, meaning it injects a damaged version of the coronavirus itself into the body.

The virus has been destroyed in a way that makes it unable to cause infection, but the body still recognises it as a dangerous intruder and therefore mounts an immune response which it can remember in case of a real Covid-19 infection. 

5. Janssen (Johnson & Johnson): 30million

The Government has agreed to buy 30million doses of a vaccine made by Janssen if it works.

Officials have agreed to help the company in its development of the jab by part-funding a global clinical trial. The first in-human trials of Janssen’s jab began in mid-July and are being done on adults over the age of 18 in the US and Belgium.

The jab is named Ad26.COV2-S, recombinant, and is a type of jab called a viral vector recombinant vaccine.

Proteins that appear on the outside of the coronavirus are reproduced in a lab and then injected into the body to stimulate an immune reaction.

The ‘Ad’ part of the vaccine’s name means it works using an adenovirus – a virus best known for causing the common cold – as a vehicle to transport the coronavirus genetics into the body.

6. Novavax: 60million

Britain has ordered 60million doses of a vaccine being developed by the US-based company Novavax. It will help to fund late-stage clinical trials in the UK and also boost plans to manufacture the vaccine in Britain.

Novavax’s jab, named NVX-CoV2373, showed positive results in early clinical trials.

It produced an immune response in 100 per cent of people who received it, the company said, and was safe and ‘generally well-tolerated’. 

Novavax’s candidate is also a recombinant vaccine and transports the spike proteins found on the outside of the coronavirus into the body in order to provoke the immune system. 

7. Imperial College London: Unknown quantity

Imperial College London scientists are working on Britain’s second home-grown hope for a jab. The candidate is slightly behind Oxford’s vaccine in terms of its progress through clinical trials, but is still a major player.

The UK Government is understood to have agreed to buy the vaccine if it works but details of a deal have not yet been publicised. 

Imperial’s jab is currently in second-phase human trials after early tests showed it appeared to be safe. 

Imperial College London will try to deliver genetic material (RNA) from the coronavirus which programs cells inside the patient’s body to recreate the spike proteins. It will transport the RNA inside liquid droplets injected into the bloodstream. 

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