Adrian Hill: ‘This is the breakthrough tool — vaccines against malaria’

Early in the Covid pandemic, Adrian Hill, head of Oxford university’s Jenner Institute, needed to find a company to roll out his group’s vaccine. There was a condition: the partner had to charge little in low- and middle-income countries, so that the vaccine wouldn’t be limited to the rich. “If there’s one thing that drives many of us here, the word is inequity,” says Hill, a slight, fast-talking 63-year-old.

The partner he found, AstraZeneca, went further — selling the Covid vaccine at cost in rich countries too during the pandemic. But the generosity backfired. Oxford’s vaccine was soon under siege, its safety wrongly questioned. “It was far more hassle than we expected.” The US financial press “wouldn’t leave us alone. They clearly didn’t like the idea of a low-cost vaccine, undercutting the market”. While other vaccine-makers made billions of dollars in profits during the pandemic, the Oxford vaccine failed to get approval in the US.

It was bad enough that “we weren’t selling an American vaccine in America. But selling it at nearly a tenth of the price of some other products is . . . ,” Hill pauses, “ . . . relevant.” In hindsight, would he do things differently? “It would be reasonable to charge a commercial price in rich countries.”

Yet Covid may just be a warm-up act for Hill. Since the early 1990s, he has been searching for a malaria vaccine. In 2020 malaria killed more people in Africa than Covid-19 did. Indeed, as attention switched, deaths from malaria rose — to 627,000, mostly young children. Early trials showed Oxford’s vaccine is 77 per cent effective in preventing clinical malaria over a year, and a forthcoming paper will conclude that a booster jab can extend this period substantially.

“If you’d asked me 15 years ago, ‘can you eradicate malaria with vaccines to the fore?’, I wouldn’t have been sure. Today I’m sure. This is the breakthrough tool — vaccines against malaria . . . If you get 80 per cent of malaria deaths prevented by vaccination, you should be able to knock deaths down to maybe 50,000-10,000 a year by the end of this decade. Then in the 2030s, I anticipate that we’ll be trying to eliminate malaria seriously with vaccines.”

That would rank among our age’s milestones, at a time when climate change and humans’ treatment of nature otherwise threaten to increase disease outbreaks. Malaria may have accelerated the fall of the Roman empire; it probably killed Dante and Oliver Cromwell; it led to the invention of the gin and tonic (to mask the taste of the drug quinine). Although driven from rich countries, it plagues sub-Saharan Africa, which accounts for 96 per cent of malaria deaths.

Without malaria, children would be healthier in general — the disease “makes you susceptible to other infections,” says Hill. African countries’ economic growth would pick up, and “population growth will probably slow . . . Everywhere in the world where you’ve improved health, people have fewer children. They’re not playing roulette, thinking a third or half of their children are going to die.”

Covid showed that vaccines can be approved and launched quicker than anyone thought. Hill’s team has pressed the World Health Organization to repeat the pace. “There’s backtracking already . . . There’s a child dying every minute. The vaccine looks safe and effective, why should we need five years?”

The WHO has agreed that safety data can be submitted in September. That could mean the vaccine, known as R21, is approved by March, and rolled out to millions of children by July. A similar malaria vaccine — RTS,S, made by UK pharmaceutical group GSK and already approved by the WHO — is due to launch next year too. “After 110 years of no malaria vaccines, like buses, two come along at once.”

Because of manufacturing issues, GSK is set only to vaccinate a few million children a year initially. Oxford, which has partnered with India’s Serum Institute, has “no limit on the number of doses we can supply next year”. Having helped the world through Covid for no profit, the Oxford team may now help some of the world’s poorest people to overcome malaria.

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Born in Dublin, Hill began his career as a geneticist. He studied how some human populations had developed adaptations in response to malaria. But it wasn’t enough. “You couldn’t go to those hospitals in the malaria season, without realising that genetics is fascinating, I’d love to understand this better, but my God, we need to do something about this now.” In Zimbabwe and Gambia, he saw “two, three children to a bed, having fits, totally anaemic, needing blood transfusions”.

Malaria parasites have mutated to escape the human immune system. “They’ve been thinking about our immune system for a lot longer than Covid, and they’re rather good at it.” The parasite that causes most deaths — Plasmodium falciparum — diverged from other strains millions of years ago.

“About 142 malaria vaccines have been made, manufactured and taken into a clinical trial. Of those, about three are plausibly usable in certain settings,” sighs Hill. Yet he never lost faith that a vaccine was possible, because those who survive exposure to malaria grow less affected by it, showing that the parasite can induce immunity.

Both the GSK and Oxford vaccines train the immune system to attack the parasites after they are injected by the mosquitoes, but before they reach the liver, where they multiply. Each mosquito injects a small number of parasites, perhaps 20. “If you clear those 20, you’ve won. If one gets through, you’ve lost. The bad news is you’ve only got minutes.”

GSK’s vaccine has efficacy of 44 per cent. This may increase if the vaccine is timed just before the malaria season, as Oxford’s is. But Hill argues the Oxford vaccine, which was developed later, is more efficiently designed.

Malaria’s massively underfunded. I worked out that a decade’s malaria vaccine funding was what was being spent a day on Covid vaccine development in the pandemic

Oxford’s Phase 3 testing continues. “We’ve given 10,000 doses of this vaccine to African children, and we’re carrying on. That tells you nothing terrible has happened.” Eventually the vaccine could be combined with a new component to reduce transmission from infected humans to mosquitoes.

Malaria funding rose sharply in the 2000s, when “there were guys like Bono shouting at presidents, saying kids are dying. And Bill Gates appeared, and started throwing billions at things. And we thought everything would be cracked very quickly, so did Bill. A lot has been cracked, it just takes more time than you would expect.” Spending on insecticides, drugs and bed nets helped to cut deaths by a third.

Still, “malaria’s massively underfunded. I worked out that a decade’s malaria vaccine funding was what was being spent a day on Covid vaccine development in the pandemic”.

So far Oxford’s malaria efforts have cost more than £100mn. Rolling out the vaccine will cost much more. “If it’s 200mn doses [a year] at $3 a dose, oops: we’re going to need $600mn.” Although there may one day be a commercial market for the vaccine, “it’s not a money-spinner to get the CEO of Pfizer out of bed”.

The Oxford team could fund its own vaccine launch, if it had charged for its Covid vaccine, but Hill has no regrets. “I think it was crazy charging $25 for a dose of Covid vaccine that you were selling on a 1 billion dose scale. How rich do you want to get as a result of a pandemic?”

Is he not jealous of BioNTech’s co-founder Uğur Şahin, whose wealth is estimated at $6.18bn? “No. He deserves it, as long as he spends it on vaccines and not on fast cars.” Hill is sceptical, however, of Şahin’s focus on tackling cancer with mRNA vaccines. “What we know about treating cancer with vaccines, you wouldn’t start with RNA.” He’s also unconvinced by BioNTech’s efforts to tackle malaria. He clearly burns with intellectual competitiveness.

Hill is more upbeat about gene drives that could kill off the mosquitoes that spread malaria. But “it makes a big difference whether [they work in] 50 years’ time or five years’ time.”

Covid vaccine rollout has stalled in parts of Africa. Would a malaria vaccine be different? “Vaccine uptake rates [for other diseases] are higher in most countries in sub-Saharan Africa than in many parts of Europe . . . I’m pretty confident that’s not going to be one of our big problems.”

Hill was married to Sunetra Gupta, an Oxford professor of theoretical epidemiology who became a leading critic of lockdowns. The couple separated in 2017. Are his views on lockdown . . . ? “Different. I’m being very diplomatic.”

The Covid vaccine was the first deployed vaccine that Hill had worked on. An Ebola vaccine, accelerated in a 2013 outbreak, was never tested; a rival drug was approved first. “I’m told it was toss-of-coin which one they tested first. They didn’t test ours, because by the time they’d done the trial there wasn’t any Ebola left.” That is the “tragedy of outbreak pathogen vaccines” — often by the time they’re ready, they aren’t needed.

Did missing out on the Ebola vaccine double Hill’s motivation to succeed with malaria? “If you reacted like that to unfortunate things happening, you wouldn’t be doing malaria vaccines for 25 years.” There is always another challenge. The Sudan strain of Ebola has no approved vaccine; Oxford has a candidate. The Jenner Institute’s other targets include vaccines for cancer.

There may be another pandemic. “It may not be as bad as Covid — it hopefully, probably won’t be — but it could be worse. If Covid had the mortality rate of Ebola, at least one of us wouldn’t be sitting here.” It’s clear to me which one of us would be missed more.