By ITV News Multi-Media Producer Narbeh Minassian
One day, the Covid-19 pandemic will come to an end – but how soon that day comes depends greatly on the progress of our vaccines.
There are more than 200 vaccines in development around the world, nearly 50 of which are in human trials.
The scale and speed of scientific efforts is unprecedented and we already have reason for genuine optimism less than a year since the first outbreak.
US firms Pfizer and Moderna have both reported initial results that show 95% and 94.5% protection against the virus, respectively.
Closer to home, Oxford University's vaccine can prevent up to 90% of people contracting coronavirus and getting seriously ill, with some indications that it can also prevent people passing the virus to others.
But that doesn’t mean we can expect an imminent return to normal life, with some important final safety assurances and a massive logistical operation required to vaccinate the population.
So just how far have we got with vaccines and what obstacles are left to overcome?
Which are the most advanced vaccines?
As mentioned, the work of US drug giant Pfizer and German biotech firm BioNTech has shown great promise, proving 95% effective in immunising against the virus.
And Moderna’s results are equally impressive at 94.5%.
Of those tested for Moderna’s vaccine candidate, 42% were over 65 or were high risk - 5,000 had diabetes, obesity or heart problems – and 37% were from ethnic minority communities.
As ITV News’ Health Editor Emily Morgan pointed out, it is “significant” that such large numbers were tested in these categories.
Data released at the end of November suggested its vaccine could even offer 100% protection against severe cases.
The signs so far are also very good for Oxford University’s potential vaccine.
More than 20,000 volunteers are participating in trials for the Oxford vaccine, in countries including the UK, South Africa, Brazil and Kenya. It is anticipated that 19 million doses will be available in the UK before the end of the year, if it is approved by the regulatory body, with each vaccinated person requiring two doses. Scientists working on the jab found that when half a dose is given, followed by a further full dose, the vaccine was 90% effective.
Early data for Russia’s candidate suggests it is 92% effective, the country’s sovereign wealth fund said, though some critics fear the vaccine has been rushed.
The phase three trials evaluated efficacy among more than 16,000 volunteers who received the vaccine or placebo 21 days after the first injection.
Of the 48 vaccines being tested in human trials globally, 11 are in Phase 3 – the most advanced stage of trials, when tens of thousands volunteer for testing.
Out of these 11 candidates, the UK has already ordered millions of doses from five. These are:
Moderna - 7 million Pfizer - 40 million Oxford University - 100 million Novavax - 60 million Janssen - 30 million
Will we be able to distribute the vaccines?
Rolling out millions of vaccines to the UK’s 66 million-strong population is no small feat, especially when considering Pfizer, Moderna and Oxford University are developing candidates that need two doses.
The vaccine developed by Pfizer needs to be stored at -70C and has to be taken in two doses three weeks apart, and will only become effective one week after the final jab.
Keeping the vaccine at such a low temperature presents an obvious challenge when it comes to distribution, particularly for countries with smaller economies.
This is where Moderna’s candidate is slightly preferable, as it only need to be kept at -20C and will last for 30 days in a fridge after defrosting.
Better than both, however, is Oxford's vaccine, which can be stored at fridge temperature. Their vaccine can be transported and distributed more easily, and will be easier to store in lower-income countries.
Watch: How many doses has the UK ordered in total?
In a bid to smooth distribution, thousands of volunteers with no medical background at all could be trained up to administer the vaccine.
St John Ambulance will be one of the organisations delivering training to those who sign up, a representative for the charity has confirmed.
In plans leaked to the Daily Mail, St John Ambulance said future vaccine volunteers would “be trained to deliver the actual injection to patients".
They would also have to “potentially react to any immediate adverse reactions".
Dr Joshua Blight, an expert in vaccinology at Imperial College London and co-founder of baseimmune vaccines, pointed to the high number of doses manufactured globally.
“Irrespective of which one works, many millions of doses have already been manufactured for the leading candidates,” he told ITV News.
“That’s unprecedented and should restore a lot of people’s faith in the willingness of the global health community to work together.
“But even so, manufacturing enough doses for the world – and by the way not just the rich northern hemisphere but then entire global population, including low to middle-income countries – may still take a long time. We should all be patient.”
When can we return to normal life?
Professor Ugur Sahin, chief executive of BioNTech, which created the vaccine candidate in partnership with Pfizer, said it is vital to have a high vaccination rate before autumn next year to ensure a return to normal life next winter.
He added: “What is absolutely essential is that we get a high vaccination rate before autumn/winter next year, so that means all the immunisation, vaccination approaches must be accomplished before next autumn.
“I’m confident that this will happen, because a number of vaccine companies have been asked to increase the supply, and so that we could have a normal winter next year.”
Jake Baum, Professor of Cell Biology and Infectious Diseases at Imperial College London, said normal life will likely not return "in one fell swoop".
"Vaccine roll out and disease eradication on a global scale was achieved over decades for smallpox - which required many different iterations of vaccine - and is still not over the finish line for polio; the first vaccines against polio were developed in the 1950s," he told ITV News.
"If the first vaccines work well, it could be by late 2021 we will all be able to live without thinking constantly about Covid.
"If any falter or there are safety issues, it could be longer. It’s a risky game to speculate."
Optimism for a vaccine, however, is well placed and Professor Baum said "it will come".
"Life will return to normal, but we’ll get there a lot sooner if we all wear masks, observe social distancing and reduce opportunities for transmission as much as possible," he said.
"Give up now and we’ll see the already unimaginable numbers of deaths continue to soar.
"Vaccines help keep the gate closed, but aren’t great once the horse has bolted!"
How many need to have the vaccine?
Professor Stephen Evans from The London School of Hygiene and Tropical Medicine told ITV News we will need "about 80-90% of the population to have immunity" before the government can consider Covid-19 not a threat.
He said some of that would come from immunity developed from people who have already had the virus but predicted around 70% of the population would need to be vaccinated.
If we reached that level then "herd immunity" would be achieved meaning the virus would not be able to survive in enough people to carry on sustaining itself.
Getting to that level will not be easy, studies have shown large proportions of the population in various countries would be sceptical about taking a coronavirus vaccine due how quickly it was developed and believing it will have unpredicted side effects.
A study by King's College London and Ipsos MORI carried out in August found only 53% of the population of the UK would be willing to take a coronavirus vaccine when it became 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 Blight 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”.
How they are 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 most advanced vaccines are in Phase 3, which is the final stage before any 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.