The mRNA vaccine revolution is just beginning

NO ONE EXPECTED the first Covid-19 vaccine to be as good as it was. “We were hoping for around 70 per cent, that’s a success,” says Dr Ann Falsey, a professor of medicine at the University of Rochester, New York, who ran a 150-person trial site for the Pfizer-BioNTech vaccine in 2020.
Even Uğur Şahin, the co-founder and CEO of BioNTech, who had shepherded the drug from its earliest stages, had some doubts. All the preliminary laboratory tests looked good; since he saw them in June, he would routinely tell people that “immunologically, this is a near-perfect vaccine.” But that doesn’t always mean it will work against “the beast, the thing out there” in the real world. It wasn’t until November 9, 2020, three months into the final clinical trial, that he finally got the good news. “More than 90 per cent effective,” he says. “I knew this was a game changer. We have a vaccine.”
“We were overjoyed,” Falsey says. “It seemed too good to be true. No respiratory vaccine has ever had that kind of efficacy.”

The arrival of a vaccine before the close of the year was an unexpected turn of events. Early in the pandemic, the conventional wisdom was that, even with all the stops pulled, a vaccine would take at least a year and a half to develop. Talking heads often referenced that the previous fastest-ever vaccine developed, for mumps back in 1967, took four years. Modern vaccines often stretch out past a decade of development. BioNTech – and US-based Moderna, which announced similar results later the same week – shattered that conventional timeline.
Neither company was a household name before the pandemic. In fact, neither had ever had a single drug approved before. But both had long believed that their mRNA technology, which uses simple genetic instructions as a payload, could outpace traditional vaccines, which rely on the often-painstaking assembly of living viruses or their isolated parts. mRNA turned out to be a vanishingly rare thing in the world of science and medicine: a promising and potentially transformative technology that not only survived its first big test, but delivered beyond most people’s wildest expectations.

But its next step could be even bigger. The scope of mRNA vaccines always went beyond any one disease. Like moving from a vacuum tube to a microchip, the technology promises to perform the same task as traditional vaccines, but exponentially faster, and for a fraction of the cost. “You can have an idea in the morning, and a vaccine prototype by evening. The speed is amazing,” says Daniel Anderson, an mRNA therapy researcher at MIT. Before the pandemic, charities including the Bill & Melinda Gates Foundation and the Coalition for Epidemic Preparedness Innovations (CEPI) hoped to turn mRNA on deadly diseases that the pharmaceutical industry has largely ignored, such as dengue or Lassa fever, while industry saw a chance to speed up the quest for long-held scientific dreams: an improved flu shot, or the first effective HIV vaccine.

Amesh Adalja, an expert on emerging diseases at the Johns Hopkins Center for Health Security, in Maryland, says mRNA could “make all these applications we were hoping for, pushing for, become part of everyday life.”
“When they write the history of vaccines, this will probably be a turning point,” he adds.
While the world remains focused on the rollout of Covid-19 vaccines, the race for the next generation of mRNA vaccines – targeted at a variety of other diseases – is already exploding. Moderna and BioNTech each have nine candidates in development or early clinical trials. There are at least six mRNA vaccines against flu in the pipeline, and a similar number against HIV. Nipah, Zika, herpes, dengue, hepatitis and malaria have all been announced. The field sometimes resembles the early stage of a gold rush, as pharma giants snap up promising researchers for huge contracts – Sanofi recently paid $425 million (£307m) to partner with a small American mRNA biotech called Translate Bio, while GSK paid $294 million (£212m) to work with Germany’s CureVac.

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