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Better Vaccines Are in Sight — for the Next Pandemic

Better Vaccines Are in Sight — for the Next Pandemic

Tuesday, 3 May, 2022 - 05:00

Arcturus Therapeutics, a San Diego biotech company, may have just laid out a template for how to make vaccines for the next pandemic. Its new vaccine, which uses self-copying mRNA, appears to work well against current strains of Covid. It’s just that the product is coming in too late to matter in the current pandemic.

But data from a large clinical trial suggest the technology should be explored for the next one — and it may have many other uses, too.

In a study that enrolled more than 16,000 people, Arcturus’s “self-amplifying” mRNA vaccine was 95% protective against severe disease and death and about 55% effective in preventing symptomatic Covid. That last result that might sound low, but it’s reasonably comparable to the current efficacy of the Pfizer and Moderna shots. Those vaccines seemed more effective at first, because they were tested against the original, less contagious strain of the virus.

Arcturus’s stock was down 20% on the release of its data, probably because, barring a new trial with outstanding data on the vaccine’s value as a booster against Covid-19, it won’t soon make inroads in the U.S. vaccine market.

But Arcturus is smart to be refining a next-generation technology that promise vaccines that are faster to make and distribute than existing mRNA shots.

Like Moderna’s and Pfizer’s mRNA vaccines, Arcturus’s saRNA shot carries the genetic code for the coronavirus’s spike protein, which human cells are tricked into making so that the immune system can learn to fend off the virus. But saRNA also includes the code for the virus’s replication machinery, the enzymes that can make copies of that code. This means that as the cell churns out a spike protein, it is being fed copies of the recipe for making more of it.

This self-amplifying (some companies say “self-replicating”) quality provides a few key advantages. Doses of saRNA vaccines can be much smaller than what’s required for an mRNA vaccine. Moderna’s and Pfizer’s mRNA shots are 100 and 30 micrograms, respectively, whereas Arcturus’s shots are just 5 micrograms. In an emergency — a future coronavirus or flu pandemic, say — significantly smaller doses could mean many more available to quickly vaccinate more people, ideally at a lower cost. Arcturus’s technology also enables the vaccine to be freeze-dried, so it would be easier to send around the world than Pfizer’s and Moderna’s, which currently need to be stored at subzero temperatures.

And because these vaccines stick around in the body longer than conventional mRNA vaccines do, they expose the immune system to an antigen for longer. Those extra days of target practice should lead to longer-lasting, broader immune-memory response. In theory, that could translate into more time between boosters, says Deborah Fuller, a professor at the University of Washington School of Medicine.

But that’s only a theory for now. The efficacy data from Arcturus’s study, conducted in Vietnam, extends only two months post-vaccination. That’s not enough time to observe the vaccine’s memory-cell response. An ongoing booster trial should give a better idea of the duration of protection, Arcturus says.

This vaccine has downsides, too. The strands of RNA needed to encode both a protein and the replication machinery are roughly three times longer than those in an mRNA vaccine. Correctly stringing together 15,000 bases and then squeezing that big ball of genetic yarn into a lipid nanoparticle isn’t a trivial challenge.

But Arcturus’s results demonstrate that it’s feasible. The saRNA vaccines developed for Covid are described by industry insiders as a bit rough and ready. None of the players testing the technology in the pandemic had previously focused on self-amplifying techniques. Arcturus’s expertise, for example, had been in packaging various types of RNA into lipid nanoparticles. While delivery is a critical component to its success, the biotech’s ability to scale up its vaccine suggests making it might not be as daunting as many had thought.

The Arcturus data also suggest that the technology could be extended against many other viruses, says Robin Shattock, head of mucosal infection and immunity at Imperial College London. And because it can use low doses, it may offer a better way to combine vaccines against various viruses into a single shot.

Still more exciting is the prospect of one day using mRNA as a drug.

A decade ago, when Moderna was created as an mRNA biotech, it was selling the promise of mRNA therapeutics, not vaccines. It’s goal was to use mRNA to turn human cells into drug factories, capable of churning out missing or beneficial proteins. Vaccines do this for a day or two — just long enough to dangle a viral protein in front of the immune system. But mRNA drug therapies would need to stick around longer and generate more proteins. So far, that has been much harder to achieve.

Creating a drug that is potent and longer-lasting might be easier with saRNA than with conventional mRNA technology. In the past year, several biotech companies, including Strand Therapeutics and Replicate Bioscience, have attracted sizable investments from venture capital and pharma companies to push saRNA-based drugs into the clinic. Big pharma seems to be evaluating the technology, too: Shattock of Imperial College founded VaxEquity, a biotech that is working with AstraZeneca on saRNA treatments for a wide range of diseases.

Data on the first saRNA therapies aren’t expected for another year or more.

Of course, saRNA should not be the only technology being readied for a future pandemic. But it’s reassuring to see what a strong option it might be — and to see money flowing into its potential to fight everyday diseases.


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