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In the last two decades, three major pandemic threats have been triggered by coronaviruses. In 2003, there was Sars, which killed 774 people. This was followed nine years later by Mers, which has killed 858 people to date. In 2020, along came Covid-19, which so far has killed more than 2.5 million people. If recent history is anything to go by, it’s a given that more coronaviruses will spill over from animals into humans, potentially triggering another global crisis.
Scientists are already working on ways to stop the next pandemic before it has a chance to cause so much death and destruction. One approach is to create a universal vaccine: a jab that can protect against a whole range of different viruses, or virus variants.
Ted Ross, the director of the Center for Vaccines and Immunology at the University of Georgia, has been developing a universal flu vaccine for the past 15 years. In 2019, his team was awarded one of the largest contracts ever given out by the National Institutes of Health to develop such a vaccine. This was back when flu was pegged as “the thing” to cause the next pandemic, Ross says. The way that flu vaccines are designed right now means that they need tweaking every year in anticipation of which strains will predominate in that coming flu season. But a longer-lasting solution would be a vaccine that protects against all strains – and could potentially stop a flu pandemic in its tracks. Attempts so far have been largely fruitless: no universal flu vaccine has made it all the way to approval.
In March of 2020, when it became clear that Covid-19 wasn’t going away, Ross’ team switched to working on a universal coronavirus vaccine. Their approach involves focussing on regions of the Sars-CoV-2 virus that are important for stimulating antibodies that the body uses to defend against a broad range of viruses. They use algorithms to analyse the important parts of multiple virus strains and assemble them into a single vaccine. “Now that we’re starting to see more variants come up, it starts to give us a chance to really test against a more broad reaction of strains, which is what’s going to be needed to know if it’s actually universal or not,” Ross says. They are planning to start the first trials in the summer of 2021.
Every time a virus makes a copy of itself, tiny alterations to its genetic code slip in. Most of these mutations make no difference to how the virus behaves, but a mutation in the wrong place could change a lot. Mutations to the spike protein – the part of the virus that it uses to hook on to and enter host cells – are particularly worrying. Three of the most widely-used vaccines on the market (Pfizer/BioNTech, Oxford-AstraZeneca and Moderna) all operate by prompting the body to create antibodies that target the spike protein. In the South Africa variant, the genetic code behind the spike protein was so altered that the Oxford-AstraZeneca vaccine may offer little protection – as low as ten per cent – against mild and moderate disease, one preprint has shown.
A universal vaccine, in theory, would be unaffected by these mutations. In order for a vaccine to be considered variant-proof, it may need to target a part of the virus less prone to change. Unlike the spike protein, which is frustratingly liable to change, the nucleocapsid protein – an internal protein found in all known human coronaviruses that helps the virus to replicate – has a low mutation rate. (This may be because mutations in this protein often disrupt the structure of the molecule, which then makes the virus less fit for replication and transmission, so the fewer changes in the amino acid structure of the nucleocapsid protein, the better for maintaining a viable virus).
One company taking this approach is Osivax, a French biotech firm, which is working on a vaccine that targets the nucleocapsid. Its vaccine triggers a strong immune response in the form of cytotoxic T cells, which destroy any infected cells before the virus is able to multiply and release itself into the body. Another, myNEO, a Belgian biotech company, is using computational algorithms to look through available coronavirus sequences to find targets across all the virus’s proteins which appear to be essential for the virus to survive. So far its vaccine has proven to not lose any efficacy against any variant of the virus, says myNEO CEO Cedric Bogaert. He expects to have the vaccine on the market in five years.
Pamela Björkman’s lab at Caltech is working on a vaccine platform which involves taking the tips of spike proteins from eight different coronaviruses and attaching them to a particle called a mosaic nanoparticle. When they injected the vaccine into mice, Björkman’s colleagues found that the animals made antibodies that reacted to all of the spike proteins of the coronaviruses – including some not present on the surface of the nanoparticle. Björkman says she is still waiting on funding for human trials.
Whether a universal coronavirus vaccine can be made depends on who you’re talking to; those who have been in the universal vaccine field for a long time remain cautious. Ross has hit enough dead ends in the hunt for a universal flu vaccine that he knows one for coronavirus isn’t around the corner. To start with, there’s a problem with how you might define ‘universal’. A lot of people use the word pretty loosely, Ross says. The term implies that you will be able to protect against all strains all the time – that’s a high bar.
“The development of a vaccine – or even antibodies for that matter – that are really pan-coronavirus, that neutralise and protect against every single coronavirus, that’s probably not going to be possible, given the massive diversity,” says Laura Walker, chief scientific officer of Adagio, a company that is developing a monoclonal antibody therapy that targets coronaviruses beyond Sars-CoV-2. The therapy is essentially a drug treatment that works by mimicking the behaviour of the human immune system to neutralise the virus. Walker says focusing on subtypes within the coronavirus family is a more realistic approach.
A universal vaccine could be designed to elicit a class of antibodies called broadly neutralising antibodies – molecular entities that can bind and neutralise many different viral strains, instead of just one. But they’re hard to find. “They’re not just readily induced by infection, people aren’t just making these antibodies,” Walker says. “We had to mine over a thousand antibodies to find one.”
“The development of antibodies in vaccines that are effective against subfamilies of viruses, for example the Sars family of viruses, that is much more feasible,” she says. And this is what her company has done: Adagio has discovered antibodies that are essentially pan-Sars, Walker says. It did this by isolating antibody-producing B cells from a person who had been infected with Sars-CoV-1 back in 2003. Scientists at the company then looked for antibodies that neutralised both the Sars virus, Sars-CoV-2 and other potentially emergent coronaviruses found in animals, like bats. The company plans to work on a coronavirus vaccine with other groups using the antibodies that they’ve developed.
Wayne Koff, the CEO of the Human Vaccines Project, an international nonprofit with the goal of decoding the human immune system, agrees with this approach. The path to making a universal vaccine should be step-wise, he says: starting with a vaccine that works against a single virus, moving on to a pan-coronavirus vaccine against a subset of the coronaviruses, then finally a universal vaccine.
Whatever happens, it’s going to take a long time for such a vaccine to appear on the market. But time is also not on our side; as rapid as vaccine development for Covid-19 was in the past year, “it was too late,” Koff says. The way he sees it, we actually got pretty lucky with Sars-CoV-2; despite being easy to pass around, it’s not very deadly. What about when the next coronavirus outbreak comes along, with a virus as transmissible as Sars-CoV-2 and as deadly as Sars-CoV, the coronavirus that caused the Sars epidemic in 2003?
Koff is calling for a global effort to come up with a universal vaccine. This will mean roping in other scientific disciplines, such as supercomputing and machine learning, to offer their expertise in order to expedite the process; for example, by helping to identify common antigenic targets shared by all coronaviruses. “We have the tools now to be able to do this,” he says. “It’s really a question of society; if we have the wherewithal to do it.”
Ross agrees. If we don’t spend the money on it now, we won’t be ready when the crisis hits – you can’t build the ship while you’re trying to steer it, he says. “There’s a whole zoonotic world that we can’t control. And they’re going to introduce strains into the human population that we have no way of predicting or getting ahead of.”
Grace Browne is a science writer at WIRED. She tweets from @gracefbrowne
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