Breakthrough COVID vaccine tech could help defeat other diseases

The initial success of so-called messenger ribonucleic acid vaccines in late-stage trials by Moderna as well as Pfizer and its German partner BioNTech is the first proof the concept works. Moderna’s vaccine went from gene sequencing to the first human injection in 63 days. With BioNTech and Pfizer’s COVID-19 candidate on a similar trajectory, both could win…

By John Miller and Ludwig Burger

ZURICH/FRANKFURT, Nov 16 (Reuters) – Breakthrough technologythat transforms the body into a virus-zapping vaccine factory ispoised to revolutionise the fight against COVID-19 but futurepandemics and even cancer could be next, scientists say.

The initial success of so-called messenger ribonucleic acid(mRNA) vaccines in late-stage trials by Moderna as wellas Pfizer and its German partner BioNTech isthe first proof the concept works.

Both experimental vaccines had efficacy rates above 90%based on interim findings, which was far higher than expectedand well above the 50% threshold U.S. regulators insist upon forvaccines.

Now scientists say the technology, a slow-motion revolutionin the making since the discovery of mRNA nearly 60 years ago,could speed up the development of new vaccines.

The traditional method of creating vaccines – introducing aweakened or dead virus, or a piece of one, to stimulate thebody’s immune system – takes over a decade on average, accordingto a 2013 study. One pandemic flu vaccine took over eight yearswhile a hepatitis B vaccine was nearly 18 years in the making.

Moderna’s vaccine went from gene sequencing to the firsthuman injection in 63 days.

With BioNTech and Pfizer’s COVID-19 candidate on a similartrajectory, both could win regulatory approval this year, barely12 months since the coronavirus first emerged.

Other companies are pursuing the technology such asGermany’s CureVac also has an mRNA vaccine candidate,though has yet to start a late-stage trial and is hoping it willget the green light after July 2021.

“We’ll look back on the advances made in 2020 and say: ‘Thatwas a moment when science really did make a leap forward’,” saidJeremy Farrar, director of the Oxford University ClinicalResearch Unit, which is backed by the Wellcome Trust.

THE LAST LAUGH

Discovered in 1961, mRNA carries messages from the body’sDNA to its cells, telling them to make the proteins needed forcritical functions, such as coordinating biological processeslike digestion or fighting disease.

The experimental vaccines from Moderna as well as Pfizer andBioNTech use lab-made mRNA to instruct cells to make thecoronavirus’s spike proteins, which spur the immune system intoaction without replicating like the actual virus.

Back in 1990, scientists managed to get mice to generateproteins by injecting mRNA, an early sign of the technology’spotential.

But early proponents such as Katalin Kariko, aHungarian-born scientist and senior vice president at BioNTech,were hampered by obstacles such as mRNA’s instability in thebody and its propensity to cause inflammatory responses.

A breakthrough came around 2005 when Kariko, along withcolleagues at the University of Pennsylvania, figured out how todeliver mRNA without kicking the immune system into overdrive.

Still, it took another 15 years – and a pandemic thatbrought the world’s economy to its knees – to reach the cusp ofsuccess. Kariko said her years of dogged pursuit once made herthe butt of jokes for some university colleagues.

“The last time they laughed at me and ridiculed me was whenthey learned that I was going to join BioNTech seven years agoand they realised this company (didn’t) even have a website,”she told Reuters. “But now, they learn of BioNTech and that wecan do good things.”

Kariko said her life’s work could pay dividends, not justagainst COVID-19, but other diseases.

“It could be easier sailing for the next anti-viral product,a vaccine for influenza and other infectious disease,” saidKariko, whose daughter is a U.S. Olympic gold medalist rower.

CANCER NEXT?

Moderna and BioNTech, for example, are also applying mRNAtechnology to experimental cancer medicines.

Biontech is testing an anti-melanoma mRNA with Swisspharmaceutical giant Roche in a Phase II trial.Among Moderna’s most advanced projects, besides its COVID-19vaccine, are mRNA compounds to treat ovarian cancer orMyocardial ischemia, which are also in the second test phase.

None of the potential mRNA cancer therapies have reached thecritical large-scale Phase III trials, however, and Karikoacknowledges that cancer presents a bigger challenge.

While a virus is a foreign intruder, cancer cells, howevermalignant, come from within the body, making them tougher toseek out and expose so they can be attacked.

“Sometimes cancer is just caused by gene and chromosomeduplication and then everything about it looks normal and thecell is just dividing more than it should,” she said.

For vaccines against infectious diseases, the pharmaceuticalindustry’s traditional approach has been to whip them up inlarge bioreactors, a time-consuming, expensive process infacilities that can cost up to $700 million to build.

By contrast, Zoltan Kis, an Imperial College Londonresearcher who models vaccine manufacturing, estimates that onefive-litre bioreactor inside a $20 million facility could make abillion doses of some kinds of mRNA vaccines a year.

Drug manufacturer Lonza, enlisted to makeingredients for 400 million doses of Moderna’s vaccine annuallyat U.S. and Swiss sites, is due to start production this yearwith manufacturing lines costing $60 million to $70 millioneach.

“We are producing mRNA at smaller scales and in smallerfacilities when compared to traditional larger-scale equipmentand facilities,” Andre Goerke, Lonza’s global lead for theModerna project, told Reuters. “The manufacturing ramp-up isquicker and more economical.”

‘ULTRA-FAST RESPONSE’

Raymond Schiffelers, of University Medical Center Utrecht inthe Netherlands, who heads a European Union programme for mRNAtherapeutics, said the major advantage of the technology wasthat vaccine developers could mount an “ultra-fast response”.

“Within weeks, testing can start, a major advantage overconventional vaccines,” he said.

The moment a pathogen’s genomic sequence is known, syntheticmRNAs can be designed that encode key parts of the virus, suchas the coronavirus’s potentially lethal spike protein.

Risks and challenges for mRNA remain.

Some candidates must be stored at extremely coldtemperatures, making delivery potentially difficult in countrieswith limited infrastructure. They also may be fragile totransport, Schiffelers said.

BioNTech’s vaccine, for example, must be transported atminus 70 degrees Celsius, though Moderna said on Monday it canship its candidate in normal refrigerators.

Francis Collins, director of the U.S. National Institutes ofHealth (NIH), which funded Moderna’s vaccine development, alsosaid mRNA vaccines may not be a silver bullet for flu, since itmutates so swiftly that reaching 90% efficacy is unlikely.

But for COVID-19, Collins said mRNA is likely to be arevolution.

“It’s clearly several months faster than any of the othermethods,” Collins said. “In a crisis moment, several monthsreally matter.”

(Reporting by John Miller in Zurich, Allison Martell inToronto, Ludwig Burger in Frankfurt, Kate Kelland in London,Michael Erman in New York, Julie Steenhuysen in Chicago andMarton Dunai in Budapest; Editing by Josephine Mason and DavidClarke)