San Diego-based biotech company Arcturus Therapeutics may have just laid out a blueprint for how to make vaccines for the next pandemic. Its new vaccine, which uses self-copying mRNA, appears to work well against existing types of COVID-19. It’s just that the product is coming too late in the current pandemic. But data from a large clinical trial suggests its technology should be explored for the next one—and it could have many other uses.
In a study enrolling more than 16,000 people, Arcturus’ “self-amplifying” mRNA vaccine was 95% protective against severe disease and death, and about 55% effective in preventing symptomatic COVID-19. That end result may sound low, but it’s pretty comparable to the efficacy of Pfizer’s and Moderna’s mRNA jabs. Those vaccines seemed more effective at first because they were tested against the original strain of Sars-CoV-2, which was less infectious.
Arcturus stock was down 20% upon the release of its data, perhaps because, barring a new trial with outstanding data on the vaccine’s value as a booster, it’s unlikely to make inroads into the US vaccine market anytime soon. But Arcturus is refining next-generation technology that promises shots that are faster to make and deliver than today’s mRNA jabs.
Like Moderna and Pfizer’s vaccines, Arcturus’ saRNA shot contains the genetic code for the coronavirus’s spike protein, which human cells are tricked into making so that the immune system can learn to stop it. But saRNA also contains the code for the virus’s replication machinery, enzymes that can make copies of that code. This means that as the cell churns out the spike protein, it is being given the formula to make more. This self-amplifying property offers some major benefits. The dose of saRNA vaccines may be much less than the amount needed for an mRNA vaccine. The mRNA shots from Moderna and Pfizer are 100 and 30 micrograms, respectively, while the shots from Arcturus are 5 micrograms. In an emergency, a significantly lower dose may mean more people are available to be vaccinated quickly at a lower cost. Arcturus’ technology also enables the vaccine to be freeze-dried, so it will be easier to ship around the world than Pfizer and Moderna, which currently need to be stored at subzero temperatures.
And because these vaccines last longer in the body than conventional mRNA vaccines, they expose the immune system to longer-term antigens. The goal should be to have a long-lasting, widespread immune-memory response in those extra days of exercise. In theory, this could translate into more time between boosters, says Deborah Fuller, a professor at the University of Washington School of Medicine.
But this is only a theory for now. Efficacy data from the study of Arcturus conducted in Vietnam occurs only two months after vaccination. This is not enough time to see a memory-cell response to the vaccine. Ongoing booster testing should give a better idea of the duration of protection.
This vaccine also has disadvantages. The strands of RNA required to encode both a protein and the replication machinery are about three times longer than in an mRNA vaccine. Binding the 15,000 bases together correctly and then squeezing that big ball of genetic thread into a lipid nanoparticle is no small challenge.
But the results from Arcturus demonstrate that it is possible. The saRNA vaccines developed for COVID have been described as a bit rough and ready by industry insiders. None of the players who tested the technique in Pandemic previously focused on self-amplifying techniques. For example, Arcturus’ expertise has been in packing different types of RNA into lipid nanoparticles. While delivery is a key component to its success, the biotech firm’s ability to scale up its own vaccine suggests that making it may not be as difficult as many thought. The Arcturus data also suggests that the technique 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 lower doses, it could provide a better way to combine vaccines against different viruses in a single shot.
More exciting still is the prospect of using mRNA as a drug one day. A decade ago, when Moderna was founded as an mRNA biotech company, it was selling the promise of mRNA therapeutics, not vaccines. Its goal was to use mRNA to turn human cells into drug factories, capable of churning out much needed missing or beneficial proteins. Vaccines do this for a day or two — just long enough for a viral protein to hang in front of the immune system. But mRNA drug therapies will need to be longer lasting and produce more proteins. So far, this has been very difficult to achieve.
It may be easier to create a potent and longer-lasting drug with saRNA than with conventional mRNA technology. Over the past year, several biotech companies, including Strand Therapeutics and Replicate Bioscience, have attracted large investments from venture capital and pharma companies to push saRNA-based drugs into clinics. Big pharma seems to be evaluating the technology too. Shtock from Imperial College founded VaxEquity, a biotech company that is working with AstraZeneca on saRNA treatments for a variety of diseases.
Data on initial saRNA treatments are not expected for another year or more. Of course, saRNA should not be the only technology to be prepared for future pandemics. But it’s reassuring to see how strong a choice it may soon be — and to see the money flowing into its potential.
Lisa Jarvis is the former executive editor of Chemical and Engineering News, who writes about the biotech, drug discovery and pharmaceutical industries.