By Multimedia Producer Narbeh Minassian
More than 170 projects worldwide are known to be actively developing a vaccine for coronavirus.
31 are already testing on humans, two of which are here in the UK.
The best hopes are that one of these efforts could produce real results before 2020's end, which would be unprecedented.
That's because vaccines usually take several years – even decades – to develop, and there is never a guarantee a perfect cure will ever be made.
Despite these odds, scientists around the world are making rapid progress under the pressures of the pandemic.
Early indications from Oxford University are that their vaccine is, so far, proving safe and inducing an immune response.
Such is the optimism around the Oxford candidate that a leading scientist said in August it could be put before regulators this year.
The first vaccine trial began just 60 days after the virus’ genetic sequence was shared by China, which a World Health Organisation (WHO) official hailed as “an incredible achievement”.
But that first vaccine to make it from the lab to the public won’t necessarily be the end of it all.
As one expert puts it to ITV News, “a golden-bullet vaccine – one shot, life-long protection – is a rarity”.
For that reason, the world needs all of its best scientific minds to pick apart the virus and produce a variety of vaccines to eventually find either a drug or combination that offers maximum protection.
So, how do we go about making a vaccine? How much progress has been made around the world? And when will one be available?
How do vaccines work?
Vaccines, to put it simply, trick your body’s immune system into thinking you’re infected with the disease.
It will then prepare a response to clear the invader from your system, and the body usually remembers the disease so any future infections will be dealt with more quickly next time.
Vaccines are made up of either the whole or part of the pathogen – in this case, that’s the Covid-19 virus.
Dr Joshua Blight, an expert in vaccinology at Imperial College London and co-founder of baseimmune vaccines, explains the logic behind why different groups are singling out the spike protein that dominates the SARS-CoV-2 virus surface.
“Think of the pathogen being like a completed jigsaw puzzle,” he told ITV News. “The way the immune system recognises and remembers the virus is as individual pieces, not as a whole puzzle. “As a vaccine developer we need to decide which pieces of the puzzle to use in a vaccine to best ‘mimic’ an infection. “This is critical since some puzzle pieces may change over time, others may be redundant to the virus, and others the immune system doesn’t even see.
"So if you design a vaccine that aims to attack one of these pieces the virus will still infect you.”
A similar approach has been taken at Oxford University, where scientists have also picked out the virus’ “club-shaped spikes”.
Professor Sarah Gilbert, who is leading the research, and her team have previously developed a vaccine for another human coronavirus disease, MERS, and their work so far has “shown promise in early clinical trials”.
How are they tested?
Once a specific method is chosen, the vaccine is then made and rigorously tested.
Generally, these tests can be done in one of two ways.
One way – known as the ‘challenge model’ – is to infect volunteers before administering the vaccine and then monitoring its efficacy.
This approach can only be done if there is already a known treatment or cure to fall back on, should the vaccine fail.
Given that there is no known cure for Covid-19, the only option for scientists is to monitor people to gauge how many are infected after immunisation.
This method needs many more volunteers and can take much longer to produce results.
Pharma companies can be licensed at any stage, ready to manufacture and distribute if trials prove successful.
What happens during trials?
The human trials at Oxford University are at a more advanced stage than any other in the world, according to the WHO's list of candidate vaccines.
Trials there are in Phase 3, which is the final stage before a vaccine can be made available on a large scale to the public.
University College London's Outbreak of Infectious Disease lead, Oksana Pyzik, explains what each stage involves:
Phase 1 - Different doses are given to a small number of healthy volunteers to get some idea of the appropriate dose and to ensure that the material is safe. The main purpose here is to identify the right dose for the next step in the testing process as well as rule out any major safety problems.
Phase 2 - The vaccine is administered to a larger number of people, often between 100 or 200 but sometimes in the thousands. At this stage, researchers evaluate whether the vaccine can produce a consistent immune response and monitor for potential side effects.
Phase 3 - The vaccine can be tested to measure how well it protects against natural infection. These studies often include tens of thousands of healthy volunteers to prove that the vaccine prevents the disease and identify rare problems or side effects that only show up in larger population or sample sizes. The speed of the Phase 3 trials is also dependent on the rate of infection and the R value - if infection rates are very low then the trial could drag on for months on end.
The Phase 1 trial in healthy adult volunteers began in April. More than 1,000 immunisations have been completed and follow-up is currently ongoing.
More than 4,000 participants are already enrolled in the UK, with enrollment of a further 10,000 people planned as researchers test the vaccine – known as ChAdOx1 nCoV-19.
It is hoped results of the trial might be available by September, with an effective vaccine being ready soon after.
"The biggest challenge will be to produce the vaccine candidate on a mass scale, given the final concentration of the solution can vary significantly," Pyzik added.
So where is the world at?
According to the WHO, there are 31 clinical trials in the world at the moment – spread across China, the US, Australia, India, Russia, South Korea, Japan, Canada, Germany, Cuba, and here in the UK.
These are the projects testing on humans, though there are more than 140 in pre-clinical stages worldwide.
Six are in Phase 3 - three in China, two in the US, and Oxford University - with another 12 in Phase 1.
The rest are either in Phase 2 or between Phase 1 and 2.
"Close to 140 vaccines are in development globally, including 23 in clinical evaluation, and several therapeutics in the pre-evaluation phase," Pyzik said earlier this year.
"We expect to see results at the end of this year, although we cannot predict at this stage whether these vaccines will meet the necessary standards."
Oxford University’s candidate is leading the race, WHO chief scientist Soumya Swaminathan said in June, with US biotech company Moderna “not far behind” with their project.
Professor Andrew Pollard, director of the Oxford Vaccine Group, said it is “just possible” that there may be enough clinical trial data on Oxford University’s vaccine by the end of the year.
Moderna’s candidate vaccine entered Phase 3 trials in July and Dr Anthony Fauci, the top public health expert in the US, admitted in June he is excited by the prospects in the country.
He said: “When - and I believe it will be when, not if, we get favourable candidates with good results - we will be able to make them available to the American public… within a year from when we started.”
Scientists in the US started human trials for a vaccine in March.
In May, they said early indications were that the vaccine could train the immune system to fight coronavirus.
They reported that neutralising antibodies were found in the first eight people who took part in safety trials for the experimental mRNA-1273 vaccine.
The drug, being tested by Moderna, injects a small sample of Covid-19’s genetic code into patients.
Elsewhere, pharmaceutical companies Sanofi and GSK have teamed up with the hope of making a Covid-19 vaccine available by the middle of next year.
They are hoping to enter a candidate in clinical trials in the second half of this year.
Scientists at the University of Pittsburgh School of Medicine are working on a fingertip-sized patch that could be a potential vaccine.
How are trials at Oxford University shaping up?
Results from Phase 1/2, published in July, suggest the candidate vaccine is safe and induces an immune response.
Researchers said their tests have revealed that the jab could provide double protection. It also induces strong immune responses in both parts of the immune system – provoking a T cell response within 14 days of vaccination, and an antibody response within 28 days.
Professor Andrew Pollard, director of the Oxford Vaccine Group, was happy with the results from trials so far.
"What it shows is that the vaccine both is very well-tolerated, exactly as we'd expect with this type of vaccine," he told ITV News.
"And perhaps really importantly we are seeing exactly the right type of immune responses, which we were hoping to see.
"Both neutralising anti-bodies and the type of white blood cell which we think will be important in protection.
"But, of course, at this stage we haven't got the read-out of protection because that's going to take a bit longer to get."
He said in August that the vaccine could be put before regulators before the year is over.
told BBC Radio 4’s Today programme: “I think that Chris Whitty is quite rightly being cautious, that it could take as long as that to first of all demonstrate a vaccine works and is safe and then to go through the processes of regulators looking at that very carefully to make sure everything’s been done correctly. “But it is also just possible that, if the cases accrue rapidly in the clinical trials, that we could have that data to put before regulators this year, and then there would be a process that they go through in order to make a full assessment of the data.”
The vaccine is also being trialled in South Africa and Brazil, where the rate of infection is higher and further results could be gathered more quickly.
Have there been any setbacks?
The trials for the Oxford vaccine have been paused, with Astrazeneca issuing a statement in September that the company is investigating whether a patient's reported side effect is connected with the vaccine.
The drug company did not reveal any information about the patient's condition other than to describe it as "a potentially unexplained illness".
The possible side effect reportedly occurred in a testing volunteer in Britain, who was expected to recover.
Health Secretary Matt Hancock Matt Hancock has said he is not too concerned over the setback.
The Health Secretary told LBC: “This is a normal part of a vaccine development that, when you find a problem, the system is paused while you investigate that particular problem.
“What it underlines is that we won’t bring forward a vaccine unless it is safe, no matter how enthusiastic I am for a vaccine.”
When will a vaccine be available?
As we know, vaccines usually take several years to develop. And even with an accelerated process, development of a vaccine for Covid-19 will take time.
Best estimates from experts reckon a vaccine could be available by the end of this year – with Dr Fauci “cautiously optimistic” one will be developed by early January.
The WHO is working with partners all over the world to speed-up research and development and Jake Baum, Professor of Cell Biology and Infectious Diseases at Imperial, says that the current cohort of Covid-19 vaccines are the quickest that any have ever been developed from lab to clinic to human trial.
“With all the good will and effort going on, we may actually see a vaccine available next year,” he said.
Some of the normal roadblocks in the process revolve around funding, he added, and a “considerable amount of regulation”.
“Usually it takes a human vaccine 10-20 years to reach the market from their conception in the lab,” he said. “However, these are unprecedented times and the research community is coming together to put all its focus into this. “Critically, key bottlenecks of funding and efforts by everyone to remove as many hurdles as possible that would otherwise slow vaccine development have been eased. "
Even if we remove these roadblocks, Dr Blight warned it is “impossible to tell” how long it takes to make a vaccine and when it might be made available. “Scientific research is unpredictable, it takes time and the failure bar can be high,” he said. “If an efficacious vaccine is proven by September – as some are suggesting – this would be quite amazing. “The more sober might say that a 2021 vaccine is most likely, with scaling production for mass use most likely achievable in 12 months or so – however the pharmaceutical industry are already preparing facilities for manufacture, therefore it could be quicker”
Pyzik said scientists around the world are "working around the clock".
"Researchers hope to achieve seven to ten years worth of research in only a few months," she said.
"The best-case projections suggest that a vaccine may be available by mid-2021, about 12-18 months after the virus first emerged."
Professor Robin Shattock, who is leading Imperial's vaccine development, shared a similar view.
"Assuming that the funding is there to purchase that vaccine, we could have that vaccine rolled out across the UK in the first half of next year,” he said in mid-July.
Sir Mark Walport, the chief executive of the newly formed UK Research and Innovation, said in late June that large-scale vaccination against coronavirus was “extremely unlikely until next year”, but significant trials may be starting now and into the autumn.
Asked if there may never be an effective vaccine, he said: “Nothing is guaranteed, but there is natural immunity to this virus in the sense that people’s immune system does actually bring it under the control, so the very fact that we get better is because our immune system is responding.
“So, I think we would be unlucky if there wasn’t a vaccine that worked eventually, but nothing in life is absolutely guaranteed.”
Is there any cooperation between countries to develop a vaccine?
The search for a vaccine is an international effort.
A WHO official says they have “stressed the need for collaboration”, insisting a “collective approach” will ensure speedy development and fair distribution.
A group of 130 scientists from the US, Canada, Italy, Austria, South Korea, Japan and other countries came together in April to continue efforts to share data.
“We believe these efforts will help reduce inefficiencies and duplication of effort,” the group declared on April 16.
“And we will work tenaciously to increase the likelihood that one or more safe and effective vaccines will soon be made available to all.”
The Covid-19 Technology Access Pool has been launched by the WHO to compile shared information in one place.
In early June, the United Nations and the International Red Cross and Red Crescent Movement all called for “unity to scale up efforts to develop, test, and scale-up production of safe, effective, quality, affordable diagnostics, therapeutics, medicines and vaccines”.
They asked governments, the private sector, and international organizations and civil to unite towards "a people's vaccine".
Dr Blight said that the UK research community has been “incredibly generous” with sharing ideas, information about the Covid-19 virus and the raw materials of vaccine research.
“Emerging collaborations between researchers with access to technology and clinicians holding serum banks, allowing team of scientists to look at populations exposed to Covid-19 is a good example where sharing has occurred at an unprecedented pace that would not normally be seen in normal times. “The UK community is generally very open and shares resources, so that is not to say this wouldn’t normally happen. “But the rapid mobilisation of government funding and community spirit has super charged the pace.”
Pyzik shared this optimism, pointing to the "world record" speed at which scientists managed to progress from discovering the virus' genome sequencing to the first human trials.
"Scientists from all over the world have been sharing genome sequencing of the virus to monitor whether significant mutations or strains have evolved," she added.
"Despite some initial media reports, it does not appear that significant mutations have occurred to identify a stronger or weaker strain of the virus."
What about Russia's vaccine?
Despite serious concerns over Russia's vaccine, which President Vladimir Putin says has been given to his daughter, preliminary results from trials suggest the candidates who took doses experienced no serious adverse side effects and that it was effective.
The Russians claim it is the world's first vaccine, which was developed at the Gamaleya Research Institute.
It has been registered before undergoing Phase 3 trials - when thousands are involved in tests that normally last for months.
The trial results, published in the Lancet, found the vaccine did cause the body to develop antibodies to Covid-19.
Researchers did, however, note a number of limitations to their study - including that it had a short follow-up. It was also a small study, while some parts of the trials included only male volunteers, and there was no placebo or control vaccine.
Scientists also noted that despite planning to recruit healthy volunteers aged 18–60, in general, their study included fairly young volunteers, on average in their 20s and 30s.
How do we know a vaccine will be safe?
Vaccines go through various phases of development and testing and the final phase reveals the level of safety and efficacy profile of the product.
After that, the vaccine needs to go through a review by the national regulatory authority and an ethics committee, who will decide if the vaccine is safe and effective enough to be put on the market.
This is a standard procedure in developed countries like the UK, but the WHO assure the world will have access to a safe vaccine once available.
An official said: “In emergency situations, such as the current one, and for countries whose regulatory authorities are under-resourced, WHO supports the process by running ‘joint reviews’ usually involving independent experts from strong regulatory authorities.”
“Safety is clearly the main concern for any vaccine developed, which is why we have to expect that any vaccine will spend a long time in human clinical trials,” said Dr Blight. “Vaccines are tested rigorously over four phases of clinical trials and at all times monitored for any adverse outcomes, from pain to more severe secondary complications. “The bar is very high for safety with all vaccines and there is no reason to suspect this will be lowered for Covid-19.”
What happens once a vaccine is found?
"During any stage of vaccine development, ideas are being licensed out to pharma companies to start plans for manufacturing and distribution if the trials prove successful," said Professor Baum.
In May, AstraZeneca announced it has the capacity to manufacture one billion doses of the University of Oxford’s potential vaccine and will begin supply in September if it proves to work.
The pharmaceutical firm said it secured the first agreements for at least 400 million doses of the vaccine.
Even though a vaccine is not ready, the firm stands ready to supply on a mass scale if results match our hopes.
It aims to conclude further deals in order to expand capacity over the next few months to “ensure the delivery of a globally accessible vaccine”.
How can coronavirus be treated in the meantime?
There isn't a specific treatment for Covid-19, but scientists are looking into the effectiveness of drugs used for other conditions.
In June, the UK announced dexamethasone, a cheap and widely available steroid, commonly used to treat arthritis, has been proven to reduce the risk of death.
The mortality rate of those with Covid-19 who end up on a ventilator is above 40%, but this figure was reduced by a third among those prescribed dexamethasone.
It also cuts the risk of death by a fifth for those on oxygen and was described by researchers as “statistically significant”.
The Government’s chief scientific adviser, Sir Patrick Vallance, hailed the findings as “tremendous news”.
Anti-inflammatory and anti-viral drug Remdesevir has also been hailed by some as an effective treatment hat can speed up recovery.
Does a vaccine mean that mean the job will be done?
While a vaccine would obviously represent a massive boost in the fight against the virus, one vaccine may not be enough for permanent protection.
"A golden-bullet vaccine – one shot, life-long protection, is a rarity," Dr Blight explains. "Much more common are vaccines that offer protection for some length of duration – usually years. "Poor duration can be because the vaccine communicates poorly with the immune system or because the virus, bacteria or parasite keeps changing. "For example, you need an annual flu shot - not because it doesn’t work, but because the virus keeps changing its coat. "So, the first vaccine may not be the best vaccine and may not be the one that is used long term." “It may be that continuous iterations of vaccine will be required until there is one that is maximally protective and lasts a long time”, he added. "Don’t underestimate that challenge. Overall, vaccinating populations may take many years.
"So, it is very important that public expectations are that the first vaccine may not be brilliant, that the first vaccine is unlikely to be the be-all and end-all of Covid-19, and that there will likely need to be many vaccines still to come." But make no mistake - vaccines work. When a good vaccine is developed, the public health consequences are enormous. "Think of Polio in the 1950s to Polio today," Dr Blight said. "Banks of people kept on artificial respirators for life, to today the virus is nearly eradicated. "No face mask, hand sanitizer or drug can do that."