The UK has ordered a total of 340m doses of potential coronavirus vaccines from six manufacturers.
The EU has done a deal said to be worth €2.4bn (£2.2bn) with one developer, while the US has orders with six companies for 800m doses under Operation Warp Speed, with options on a further 1.6bn.
Wealthy countries are paying upfront for something that has not yet been proven to work, willing to spend whatever it takes to get their economies running again.
And yet they could have backed the wrong horse. It is a lottery on an unprecedented scale.
They have rolled the dice and cannot know whether the gamble will pay off. Earlier this week, the frontrunner the UK and EU have ordered, the Oxford University-AstraZeneca vaccine, was paused after a volunteer became ill. It may not be vaccine-related, but such things can happen.
And if the wealthy nations lose their bets, they will be knocking on the door of Covax, a World Health Organization initiative set up so that all countries share the risks of vaccine development but also the benefits when one or more emerge that work.
There are an extraordinary 321 potential vaccines in development around the world, of which 32 are in clinical trials, according to the Wellcome Trust. A handful are in their last stages, involving tens of thousands of people.
Apart from the Oxford vaccine, the UK is gambling on vaccines developed by BioNTech-Pfizer, Valneva, GSK-Sanofi, Novavax and Janssen.
It has spread its bets, ordering vaccines made with four different technologies. But, says Sir Jeremy Farrar, the director of Wellcome, “we have no idea where the best vaccine that is safe and effective will come from.
“It is an inherently risky endeavour, and you cannot back on a single vaccine candidate. You have to have a portfolio, you have to be pragmatic that not all of these vaccines in late stage development will make it through.”
The world’s biggest portfolio is held by Covax, which offers a lifeline to poorer countries that could not possibly afford to buy new vaccines for their populations. For wealthy countries Covax is an “insurance policy”.
Unicef procures existing vaccines for low-income countries around the world. The United Nations children’s charity is playing a similar role in the Covid-19 pandemic. It is ordering not only potential vaccines, but essentials such as vials, syringes and fridges to be sure there are enough stockpiled before the global rush.
Gian Gandhi, who is Unicef’s Covax coordinator, said the only country likely to have anything close to the WHO initiative’s large portfolio of potential vaccines and related products was the US.
“But what that means is that any other country with a bilateral deal would likely still benefit from signing up to Covax because we don’t know which candidates will show efficacy, be licensed and be recommended for use,” he said. “As a result, the Covax facility could operate as a kind of backup … a kind of insurance policy for the country should the vaccines they have backed not demonstrate efficacy.”
So far, 78 wealthy countries have signed up for the insurance policy, including the UK. The deal is that they put money into Covax, which goes to vaccine developers that sign up to supply the initiative. Wealthy countries still get to self-fund, as Gandhi puts it.
Covax will enable developed nations to do a deal for a vaccine that works, if the ones they gambled on fail. But they will have to pay full price for it, unlike 92 low-income countries, which will be subsidised by Gavi, the global alliance for vaccines and immunisation.
In June, Gavi launched an advance market commitment that has raised $600m so far from donors. But it needs $2bn by the end of the year.
In a pandemic where countries are pulling up drawbridges and being condemned for “vaccine nationalism”, the Covax model is remarkable because it is about equity between wealthy and poor. Every country that has signed up – the US has not – will receive enough vaccine for 20% of its population, the idea being that it will go to health workers and the most vulnerable.
Dr Melanie Saville, the director of vaccine research and development at the Coalition for Epidemic Preparedness (Cepi), believes wealthier countries do want to help end the pandemic in the poorer nations too.
“We have to recognise that indeed countries have done bilateral deals with individual manufacturers,” she said. “I think it’s normal for governments to want to protect their own populations. But also we do see that governments are looking to protect the world against Covid-19.”
Cepi is investing in nine vaccines, which are part of the Covax portfolio and include many of the current contenders, including the Oxford-AstraZeneca vaccine and the vaccine being developed by the US biotech firm Moderna. Cepi has so far invested $1.4bn to support the development of these vaccines, but says a further $1bn is urgently needed.
AstraZeneca and Novavax have signed up to allow the Serum Institute of India to make up to 100m doses of their vaccines, if they are successful, that will be distributed through Covax. AstraZeneca has also guaranteed a further 300m doses for Covax.
Farrar says no country can immunise everyone of straight away. “I think it’s increasingly clear that most countries do not envisage vaccinating their whole population. I think that’s entirely appropriate for all sorts of different reasons. We wouldn’t have necessarily the doses,” he said.
No manufacturer will have the capacity to churn out all the doses needed – so how we share out the limited stocks of a vaccine over the first six months will be crucial, as will the targeting of people most at risk, Farrar added.
But, the sobering truth remains that a vaccine will not bring an end to the pandemic.
According to Gavi, vaccines at the preclinical stage – before they are given to humans – have roughly a 7% chance of succeeding, while the ones that make it to clinical trials have about a 20% chance.
Even those that succeed will not work perfectly. Few experts think we will have a vaccine that is 100% protective. Some may work better in some people than others. Flu vaccine, for example, does not work well in older people whose immune systems have become weaker with age.
It is also quite possible that some vaccines will need boosting. Antibodies generated by Covid infection have been found to fade in many people, sometimes disappearing within months.
But vaccines, such as the Oxford prototype, which are made with an adenovirus vector – a common cold virus that delivers the Covid vaccine itself – may not be easy to boost.
The immune system could recognise the cold virus and fight it off next time. That means a combination of vaccines may be needed.
Another issue is the need for ultra-low temperatures to store some of the vaccines in development – especially those using messenger RNA.
“There are a few vaccines that right now in the clinical trials seem to suggest ultra cold chain, requiring storage at temperatures anywhere between -60C to -80C,” said Gandhi. That is a headache, because those sorts of freezers are not available in most Covax countries.
In the end, says the WHO, the pandemic will be brought to a halt only if all countries can stop the virus circulating.
“Equal access to a Covid-19 vaccine is the key to beating the virus and paving the way for recovery from the pandemic,” said Stefan Löfven, Sweden’s prime minister. “This cannot be a race with a few winners.”