Fifty years ago, Sir Peter Piot opened a mysterious package sent to his Belgian lab containing a thermos. With no protective gear besides latex gloves, the young microbiologist unscrewed it and found a slurry of half-melted ice, the shards of a broken test tube, clotted blood, and ink running from a handwritten note.
The letters could still be deciphered: the blood, a physician had written from a clinic in Kinshasa, now the capital of the Democratic Republic of the Congo, was from a Belgian nun struck down by an ugly affliction he could not diagnose.
From that unsavoury soup, Piot and his colleagues would extract and discover one of the most dangerous viruses ever found: Ebola.
Watching the most aggressive-ever outbreak of the haemorrhagic fever devastate the DRC half a century later, unleashed by the rare Bundibugyo strain, the now-renowned virologist has turned his mind to the “holy grail” of prevention: treatments that work against whole families of a virus.
“I regret that we did not invest in a vaccine for the whole family – not just each virus strain,” he says. “We need to go to something that is broadly protective.”
Soon after co-discovering the strange, wormlike virus in 1976, Piot found himself in the Congo, examining the blood of a nurse racked with uncontrollable vomiting, diarrhoea and sticky black bruises around her nose, ears and mouth. His hands shook as he handled her sample, saw the cratered platelet count and came to understand the terror the virus brought: her blood work, at a cellular level, was a “catastrophe”.
Close to 8000 people have contracted the virus during the latest outbreak. There have been 3761 confirmed deaths across the Democratic Republic of the Congo and Uganda and the disease has now reached the South Ubangi province, 1000 kilometres from the outbreak’s epicentre.
With no treatments for Bundibugyo, responders have had little choice but to roll out a vaccine targeting a different type of the virus, Zaire, which Piot believes will offer at least some protection.
“It will get worse before it gets better. It’s still expanding. And the big unknown is whether it will get into a city in Congo like Kisangani. Will it go to Goma? Will it get into South Sudan? Before the end of the year there’s definitely no way it’ll be over.”
Part of the frustration is watching the global community funnel funds into the region – about $US3 billion has gushed into the DRC – and deaths still mount. Despite the influx of funds, some frontline nurses and doctors at most risk of illness are not getting paid.
“Healthcare workers have not been paid for three months. They risk their lives every single day. They’re not paid so they go and strike. I mean, I would do the same. It’s a tragedy.”
It’s a cycle Piot wants broken: new zoonotic outbreak, global panic, torched resources, eventual loss of interest, and a lapse back into complacency.
Piot visited the Doherty Institute in Melbourne this month, in part to discuss efforts to make new antivirals and multi-variant vaccines, which would be key to breaking this deadly loop.
It’s a scientific quest easier said than done. The institute’s namesake, Nobel Prize winner Peter Doherty, has said making a multi-strain vaccine is harder than putting man on the moon.
But the rockets, so to speak, are warming up. In June, scientists from the University of Cambridge announced they’d trialled a new vaccine in 39 people that could protect against a range of Sarbeco coronaviruses including COVID-19, SARS and other related viruses in bats.
Instead of crafting a vaccine tailored to one strain’s spike protein, the researchers used AI to analyse the genetics of thousands of related viruses to create a “super-antigen”: something that generates an immune response targeting common features across the whole viral family.
The impact on the immune system was “modest”, the researchers wrote in the Journal of Infection, but promising enough that the team are planning to use the same approach to tackle multiple Ebola strains. The study marked the first use of an AI-designed vaccine in people.
Piot is also an advocate for new broad-spectrum antivirals, in part due to a near-fatal COVID infection in the early months of the pandemic.
“I was in intensive care and I got long COVID. I know it’s no joke,” he says. As he struggled for breath in a ward he shared with three other gasping patients, his only gratitude was that he didn’t have Ebola. For weeks afterwards he could only whisper.
The experience convinced him we need faster-acting antivirals to handle outbreaks alongside vaccines, which can take days to kick in with an immune response.
“I’m promoting the fact that we should develop small molecule therapeutics that can treat or prevent infections on a whole family of viruses,” he says.
One of the Doherty Institute’s researchers Piot met last week, Dr Rubaiyea Farrukee, is pursuing just that. She has flipped the focus from the contours of a specific virus to the multi-viral weapons our bodies are already equipped with.
“Many people don’t know this but our bodies produce antiviral proteins all the time to fight off infection,” says Farrukee, who works with the institute’s Cumming Global Centre for Pandemic Therapeutics. “The problem is the virus can overcome it, so it’s this balancing act.”
Help tip the scales in favour of these virus-busting proteins, and fewer people get ill. “These proteins that our bodies produce are already quite broad in how they act against different viruses. They’re not specific. So, in many ways, we’re taking a lesson from nature.”
Farrukee is focused on boosting three proteins: MxA, which interrupts viral replication, IFITM3, which stops viruses getting into cells, and tetherin.
“Tetherin, for example, prevents the virus from escaping the cells by tethering them to the surface of the cell, like a rope. The name essentially gives away how it works.”
By jetting the mRNA sequences that code for these proteins into key parts of the body – such as via a nasal spray – Farrukee hopes patients’ cells will ramp up the production of these proteins. The result could be a new, fast-acting antiviral that helps arrest a huge range of respiratory diseases, such as influenza, RSV and COVID.
Such a treatment, still five to 10 years from large-scale trials in humans, would hand humanity a versatile anti-viral weapon.
“They could be the first line of defence against a pandemic from a novel respiratory virus while we’re developing vaccines in the background,” Farrukee says.
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