Who should get a coronavirus vaccine first? It’s complicated

Nicolas Asfouri via Getty Images / WIRED

The race to find a vaccine against Covid-19 is well underway. It has to be – without one, the Before Time is never coming back. More than a hundred candidates are cooking, most still preliminary. A handful are in early human studies, three in Phase II clinical trials designed to see if they actually confer immunity to the disease.

But nobody thinks finding a winner will be easy; vaccine development typically takes years. That’s time researchers and governments don’t feel like they have. Globally, more than 4 million people have gotten sick, and 280,000 have died. People sheltering in place and the closure of businesses has cost 30 million jobs in the United States alone. As the famed virologist Peter Piot wrote in an account of his own experience after getting sick with Covid-19, “the only real exit strategy from this crisis is a vaccine that can be rolled out worldwide.”

Even if scientists do develop a safe, broadly effective vaccine, nobody knows how to give it to billions of people. It’ll be scarce at first and – depending on how it works and how it’s made – potentially difficult to transport. They have to figure out how to deploy it now, so that a planet’s worth of people in desperate need will be able to get it.

One approach might be to initially give the vaccine only to members of specific groups. Of course, then someone will have to decide which groups get priority. That order will be hard to figure out. Even if the answer is “whoever is most at risk of dying,” the epidemiological data still isn’t clear on which group meets that criterion. Older people are more likely to get severely ill and die, but researchers are still trying to work out the role that children play as carriers, for example. “The more fine-grained that is, the more we can define the risk groups, both with respect to how much risk they have of getting infected and the risk of severe outcomes,” says Andreas Handel, an infectious disease modeller at the University of Georgia.

And “most at risk” isn’t necessarily the right answer. Maybe people at high risk of catching the disease but with a lower risk of bad outcomes should be first in line. That could mean prioritising people with high-exposure jobs that involve a lot of public contact, or that could mean addressing the systemic problems that have led to poorer, African American, and Latinx people facing more illness and death from Covid-19. That’s not easy. “It could be groups with underlying health conditions, or people who, because of the kind of work they’re doing, can’t avoid contact – like health care workers, police officers, grocery store workers,” Handel says.

Alternatively, maybe the vaccine should go to the groups for whom it’d do the most good, immunologically speaking. The vaccine against seasonal influenza, for example, isn’t as effective in older people. If a Covid-19 vaccine has the same limitation, that’s a big problem.

It could also be a solution. Maybe the best bet is giving the vaccine to people who mount the biggest immune response to it – young, healthy people, perhaps – to start building a roundabout sort of herd immunity. “It could be conceptually possible that it’s better to give it to age groups that don’t need it as much, but indirectly protect the other age groups,” Handel says. “The question then is, should you focus on giving the vaccine to those who don’t directly benefit the most because their risk is lower, but if they’re vaccinated, they can’t get it and pass it on to their parents?”

By the time a vaccine is available, the pandemic may have entirely new geopolitical characteristics. Researchers don’t expect that the disease itself will have changed in important ways, but if hot spots arise in countries with bad health infrastructure or a damaged civil society, that’ll make it difficult for those nations to afford a vaccine and hard for them to deploy it. “How do we make public health and ethical decisions, both within countries and globally, to ensure there’s equitable and affordable access to scarce lifesaving resources?” asks Lawrence Gostin, a health policy researcher at Georgetown University and coauthor of a recent article on vaccine distribution equity in The Journal of the American Medical Association. “Countries are likely to compete with one another for scarce vaccines and hoard them for their own citizens. How do you create and advance planning and protocol to ensure that all countries cooperate and share scarce lifesaving resources?” This isn’t just academic; during the H1N1 influenza pandemic in 2009, countries hoarded vaccines even though the disease killed 18,000 people worldwide – a horrifying number that today nevertheless manages to seem small.

Getting vaccines to poorer and socially unsettled parts of the world can be dangerous for health care workers. And parts of the world with less energy infrastructure challenge the so-called cold chain if a vaccine requires refrigeration. (An Ebola vaccine gets to people who need it in the Democratic Republic of Congo in an entirely new kind of portable cooler.)

Countries with more fragile societies also present a communications challenge. If people don’t know what’s going on, or don’t know how a vaccine works, they might refuse it. Imagine if the first time you heard about a vaccine was when people rolled into your town wearing full hazmat gear, wanting to give you a shot. “We need to be careful, even in the more advanced parts of the world, with the best and most sophisticated health care systems, about how we communicate, how we get communities to understand what’s going on,” says Chimeremma Nnadi, Global Medical Director for Vaccines at Merck and a former medical officer at the Centres for Disease Control and Prevention. “If you look at the global south, for instance, where you see systems and structures that are not as advanced, for most of those places the same suspicion around the origins of the vaccine is very free-flowing.”

One way to address a few of these problems all at once might be not to think of the solution as being only one vaccine. That’s one of the centrepieces of a new framework in an article in the journal Science this week, cowritten by Larry Corey of the Vaccine and Infectious Disease Division at Fred Hutchinson Cancer Center, John Mascola and Anthony Fauci of the National Institute of Allergy and Infectious Diseases, and Francis Collins, head of the National Institutes of Health. (That’s a heavy-hitting shared byline.) “What we outline is an approach that we feel will do what is best for the world, which is to identify as many effective vaccines as we can, to characterise their effectiveness as transparently and with as great veracity as we can, and to set up a system that allows the immediate translation of effectiveness into licensure and manufacturing and distribution into people’s arms as quickly as possible,” Corey told WIRED. “That has been a major issue for vaccines since eternity.”

Putting multiple vaccines into action could help serve many populations in lots of locations living under different conditions. “The diversity of the vaccination, the logistic aspect of things – cold chain, one dose or two doses, side effect profiles – all these things are why we want to have more than one platform and why we’re thinking about how to advance as many platforms as we can,” Corey says.

Having a bunch of approved vaccines might also help accelerate the typical curve of improvement. “History tells us that the first vaccines that get licensed generally are not the ones that are widely used. They usually get replaced after a couple years,” says Peter Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine. “We improve on them.” And the goal of multiple vaccines might also help deal with some of the competitive aspects of the race, if the various companies and labs working on the problem know that they still stand a chance of being successful even if they aren’t the first to market.

It’s not a perfect solution, for sure. In the fight against Ebola in the DRC, Gostin says, “there were two effective vaccines, but there were huge implementation problems. One: There was enormous controversy about whether it’s too confusing to deploy two vaccines that needed different doses. But even more important, you had community distrust and political violence.” That has been true for the last-mile efforts to eradicate polio too. “In both of them, the bottom line was a lot of antivaccine attitudes, public distrust, and violence against health workers and vaccine workers,” Gostin says.

The question of who will get a Covid-19 vaccine first, and how to get it to them, is central to the planning of international nongovernmental organisations like the Coalition for Epidemic Preparedness Innovation and Gavi, the Vaccine Alliance, and to national CDCs and the World Health Organisation. “Covid-19 has demonstrated over and over that for public health, for government, for economists, and for any elemental human endeavour, that we’re learning a lot,” Nnadi says. “We’re essentially building the plane as we fly it.” And so far, that plane is jetting through heavy fog, with only the ghost of a flight plan.

This story was originally published on WIRED US

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